The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exert...The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.展开更多
BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the esta...BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.展开更多
Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury models.Heme oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox...Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury models.Heme oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox homeostasis.Metformin is a classic drug used to treat type 2 diabetes that can inhibit ferroptosis.Previous studies have shown that,when used to treat cardiovascular and digestive system diseases,metformin can also upregulate heme oxygenase-1 expression.Therefore,we hypothesized that heme oxygenase-1 plays a significant role in mediating the beneficial effects of metformin on neuronal ferroptosis after spinal cord injury.To test this,we first performed a bioinformatics analysis based on the GEO database and found that heme oxygenase-1 was upregulated in the lesion of rats with spinal cord injury.Next,we confirmed this finding in a rat model of T9 spinal cord compression injury that exhibited spinal cord nerve cell ferroptosis.Continuous intraperitoneal injection of metformin for 14 days was found to both upregulate heme oxygenase-1 expression and reduce neuronal ferroptosis in rats with spinal cord injury.Subsequently,we used a lentivirus vector to knock down heme oxygenase-1 expression in the spinal cord,and found that this significantly reduced the effect of metformin on ferroptosis after spinal cord injury.Taken together,these findings suggest that metformin inhibits neuronal ferroptosis after spinal cord injury,and that this effect is partially dependent on upregulation of heme oxygenase-1.展开更多
Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebr...Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.展开更多
Intracellular communications between breast cancer and fibroblast cells were reported to be involved in cancer proliferation,growth,and therapy resitance.The hallmarks of cancer fibroblast interactions,consisting of c...Intracellular communications between breast cancer and fibroblast cells were reported to be involved in cancer proliferation,growth,and therapy resitance.The hallmarks of cancer fibroblast interactions,consisting of caveolin 1(Cav1)and mono-carboxylate ransporter 4(MCT4)(metabolic coupling markers),along with IL-6,TGFB,and lactate secretion,are considered robust biomarkers predicting recurrence and metastasis.In order to promote a novel phenotype in normal fibroblasts,we predicted that breast cancer cells could be able to cause loss of Cavl and increase of MCT4,as well as elevate IL 6 and TGF in nearby nomal fibroblasts.We created a co culture model using breast cancer(4T1)and normal fibroblast(NIH3T3)cell lines cultured under specific experimental conditions in order to directly test our theory.Moreover,we show that long-term co-culture of breast cancer cells and normal fibroblasts promotes loss of Cavl and gain of MCT4 in adjacent fibroblasts and increase lactate secretion.These results were validated using the monoculture of each group separately as a control.In this system,we show that me tformin inhibits IL-6 and TGFB secretion and re expresses Cavl in both cells.However,MCT4 and lactate stayed high after treatment with metformin.In conclusion,our work shows that co-culture with breast cancer cells may cause signifcant alterations in the phenotype and secretion of normal fibroblasts.Metformin,however,may change this state and affect fibroblasts'acquired phenotypes.Moreover,mitochondrial inhibition by metformin after 8 days of treatment,signi ficantly hinders tumor growth in mouse model of breast cancer.展开更多
Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury.However,its effect on spinal cord injury in aged mice remains unclear.Considering the essential role of a...Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury.However,its effect on spinal cord injury in aged mice remains unclear.Considering the essential role of angiogenesis during the regeneration process,we hypothesized that metformin activates the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway in endothelial cells,thereby promoting microvascular regeneration in aged mice after spinal cord injury.In this study,we established young and aged mouse models of contusive spinal cord injury using a modified Allen method.We found that aging hindered the recovery of neurological function and the formation of blood vessels in the spinal cord.Treatment with metformin promoted spinal cord microvascular endothelial cell migration and blood vessel formation in vitro.Furthermore,intraperitoneal injection of metformin in an in vivo model promoted endothelial cell proliferation and increased the density of new blood vessels in the spinal cord,thereby improving neurological function.The role of metformin was reversed by compound C,an adenosine monophosphate-activated protein kinase inhibitor,both in vivo and in vitro,suggesting that the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway likely regulates metformin-mediated angiogenesis after spinal cord injury.These findings suggest that metformin promotes vascular regeneration in the injured spinal cord by activating the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway,thereby improving the neurological function of aged mice after spinal cord injury.展开更多
Cancer-associated fibroblasts(CAFs)are one of the most abundant stromal cells in the tumor microenvironment which mediate desmoplastic response and are the primary driver for an immunosuppressive microenvironment,lead...Cancer-associated fibroblasts(CAFs)are one of the most abundant stromal cells in the tumor microenvironment which mediate desmoplastic response and are the primary driver for an immunosuppressive microenvironment,leading to the failure of triple-negative breast cancer(TNBC)immunotherapy.Therefore,depleting CAFs may enhance the effect of immunotherapy(such as PD-L1 antibody).Relaxin(RLN)has been demonstrated to significantly improve transforming growth factor-β(TGF-β)induced CAFs activation and tumor immunosuppressive microenvironment.However,the short half-life and systemic vasodilation of RLN limit its in vivo efficacy.Here,plasmid encoding relaxin(pRLN)to locally express RLN was delivered with a new positively charged polymer named polymeric metformin(PolyMet),which could increase gene transfer efficiency significantly and have low toxicity that have been certified by our lab before.In order to improve the stability of pRLN in vivo,this complex was further formed lipid poly-γ-glutamic acid(PGA)/PolyMetpRLN nanoparticle(LPPR).The particle size of LPPR was 205.5±2.9 nm,and the zeta potential was+55.4±1.6 mV.LPPR displayed excellent tumor penetrating efficacy and weaken proliferation of CAFs in 4T1luc/CAFs tumor spheres in vitro.In vivo,it could reverse aberrantly activated CAFs by decreasing the expression of profibrogenic cytokine and remove the physical barrier to reshape the tumor stromal microenvironment,which enabled a 2.2-fold increase in cytotoxic T cell infiltration within the tumor and a decrease in immunosuppressive cells infiltration.Thus,LPPR was observed retarded tumor growth by itself in the 4T1 tumor bearing-mouse,and the reshaped immune microenvironment further led to facilitate antitumor effect when it combined with PD-L1 antibody(aPD-L1).Altogether,this study presented a novel therapeutic approach against tumor stroma using LPPR to achieve a combination regimen with immune checkpoint blockade therapy against the desmoplastic TNBC model.展开更多
Objective:Polycystic ovary syndrome(Pcos)is a pathophysiological disorder affecting reproductive and metabolic indices in females.The present study was designed to compare the efficacy of metformin and D-chiroinositol...Objective:Polycystic ovary syndrome(Pcos)is a pathophysiological disorder affecting reproductive and metabolic indices in females.The present study was designed to compare the efficacy of metformin and D-chiroinositol in PcoS patients.Methods:In a tertiary care hospital in North India,prospective observational research was undertaken on 1o0 patients with PCOS,which was diagnosed based on European Society of Human Reproduction and Embryology Guidelines and ultrasound of lower abdomen.The study involves various clinical characteristics into consideration for the determination of statistical significance(P<0.05)in PCOS patients.Student's t-test along with the association between PCOS and patients taking metformin and D-chiro-inositol,as well as their impact on various biochemical parameters,were investigated finally using Pearson Correlation Analysis.Results:This study comprises 50 patients taking metformin and 50 patients taking D-chiro-inositol in women suffering from PCOS.Body mass index(BMI)and waist-to-hip ratio(WHR)were statistically significant(P<0.05)within the groups of both metformin and D-chiro-inositol.Biochemical parameters such as luteinizing hormone(LH),follicle stimulating hormone(FSH),anti-mullerian hormone(AMH)and glycated hemoglobin(HbA1c)were found to be statistically significant(P<0.05)in both groups.LH,FSH and AMH(14.40±0.52;14.28±0.53;1.99±0.10)were comparatively lower in patients taking D-chiro-inositol as compared to metformin group(14.17±0.42;19.88±1.01;2.61±0.04).HbA1c(3.71±0.08)with P<0.05 was found to be decreased more in metformin group as compared to patients taking D-chiro-inositol(4.90±0.09).A positive correlation was found between HbAlc and LH in metformin,&HbAlc and FSH in D-chiro-inositol groups,respectively.Conclusion:The results indicate that D-chiro-inositol shows better results in reducing clinical variables involved in causing PCOS as compared to metformin whereas metformin has better glycemic control in PCOS patients.展开更多
The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resu...The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed independently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endothelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.展开更多
Objective:To compare the effectiveness of inositol and metformin on the clinical characteristics,and endocrine and metabolic profiles of infertile polycystic ovarian syndrome(PCOS)women from Vietnam.Methods:From June ...Objective:To compare the effectiveness of inositol and metformin on the clinical characteristics,and endocrine and metabolic profiles of infertile polycystic ovarian syndrome(PCOS)women from Vietnam.Methods:From June 2018 to August 2022,a randomized trial was undertaken at the Hue Center for Endocrinology and Reproduction on infertile women aged 18 to 40 years with polycystic ovarian syndrome.The clinical,endocrine,and metabolic features of these individuals were assessed before and after 3 months of treatment with 2 g of inositol or 1700 mg of metformin per day.Natural pregnancy rates,adverse effects,and tolerance of inositol were recorded.Results:The study included 171 infertile PCOS women who were eligible to participate and took part in the baseline assessment,of whom 132 women participated in data analysis after 3 months.After metformin treatment,42.1%of women with oligomenorrhea experienced regular menstruation.Metformin significantly lowered body mass index(BMI),waist circumference and testosterone levels,but had no effect on other clinical characteristics,endocrine profiles,or metabolic profiles.29.2%Of women reported experiencing side effects.21%Of them attained pregnancy,which resulted in 17.1%of live births.In the inositol group,the rate of regular cycle increased by 18.2%and the total testosterone concentration significantly decreased.In overweight/obese women with PCOS,inositol significantly decreased weight,BMI,waist and hip circumferences(P<0.05).100%Of women tolerated inositol and continued treatment.18.9%Of them became pregnant,leading to 17%of live births.Conclusions:Metformin and inositol can improve weight and waist circumference in overweight/obese infertile women with PCOS.Metformin is associated with a higher rate of regular menstruation,whereas inositol is associated with a lower rate of adverse effects.The spontaneous conception,clinical pregnancy,and live birth rates between two groups are comparable.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is among the commonest malignancies associated with significant cancer-related death.The identification of chemopreventive agents following HCC treatments with the potential to ...BACKGROUND Hepatocellular carcinoma(HCC)is among the commonest malignancies associated with significant cancer-related death.The identification of chemopreventive agents following HCC treatments with the potential to lower the risk of HCC adverse course is intriguing.Metformin,a first-line agent used in the treatment of type 2 diabetes mellitus(T2DM),has been associated with inhibition of HCC growth.AIM To determine whether metformin can prevent adverse events(i.e.,death,tumor progression,and recurrence)after any HCC treatment in T2DM patients.METHODS A systematic review of the published literature was undertaken focused on the role of metformin on outcomes in patients with T2DM and HCC receiving any tumor therapy.A search of the PubMed and Cochrane Central Register of Controlled Trials Databases was conducted.RESULTS A total of 13 studies(n=14886 patients)were included in this review.With regard to the risk of death,a decreased risk was reported in cases receiving metformin,although this decrease was not statistically significant[odds ratio(OR)=0.89,P=0.42].When only patients treated with curative strategies were considered,a more marked correlation between metformin and favorable cases was reported(OR=0.70,P=0.068).When analyzing palliative treatment,there was no statistical significance in terms of the correlation between metformin and favorable cases(OR=0.74,P=0.66).As for the risks of progressive disease and recurrence,no obvious correlation between metformin use and reduced risk was reported.When sub-analyses were performed for patients from different regions,the results for patients from Eastern countries showed a tendency for decreased risk of death in T2DM cases receiving metformin(OR=0.69,P=0.17),but the same was not seen in patients from Western countries(OR=1.19,P=0.31).CONCLUSION Metformin failed to show a marked impact in preventing adverse effects after HCC treatment.A trend was reported in T2DM cases receiving curative therapies in relation to the risk of death,especially in patients from Eastern regions.Great heterogeneity was reported among the different studies.Further large studies are required to definitively clarify the real impact of metformin as a chemopreventive agent for HCC.展开更多
BACKGROUND Gestational diabetes mellitus(GDM)refers to hyperglycemia caused by insulin resistance or insufficient insulin secretion during pregnancy.Patients with GDM have a high risk of pregnancy complications,which ...BACKGROUND Gestational diabetes mellitus(GDM)refers to hyperglycemia caused by insulin resistance or insufficient insulin secretion during pregnancy.Patients with GDM have a high risk of pregnancy complications,which can adversely affect both maternal and fetal health.Therefore,early diagnosis,treatment and monitoring of GDM are essential.In recent years,a new treatment scheme represented by insulin aspart combined with metformin has received increasing attention.AIM To explore the effects of insulin aspart combined with metformin on patients with GDM and inflammatory markers.METHODS From April 2020 to September 2022,124 patients with GDM in Sanya Women and Children’s Hospital Managed by Shanghai Children’s Medical Center were collected and analyzed retrospectively.The control group(CG)comprised 62 patients treated with insulin aspart alone,and 62 patients treated with insulin aspart and metformin formed the observation group(OG).Before and after treatment,improvement of blood-glucose-related indexes[fasting blood glucose(FBG),2-h postprandial glucose(2h PG)and hemoglobin A1c(HbA1c)],serum related factor[serum homocysteine(Hcy)],serum inflammatory cytokines[tumor necrosis factor(TNF)-α,interleukin(IL)-6 and C-reactive protein(CRP)]were compared between the two groups.The clinical efficacy,adverse pregnancy outcomes and incidence of pregnancy complications were compared between the two groups.RESULTS After treatment,the levels of FBG,2h PG,HbA1c,Hcy,TNF-α,IL-6 and CRP in both groups were significantly decreased(P<0.05),and the levels of FBG,2h PG,HbA1c,Hcy,TNF-α,IL-6 and CRP in the OG were lower than in the CG(P<0.05).The total clinical effectiveness in the OG was higher than that in the CG(P<0.05).The total incidence of adverse pregnancy outcomes and complications in the OG was significantly lower than in the CG(P<0.05).CONCLUSION Insulin aspart combined with metformin are effective for treatment of GDM,which can reduce blood-glucoserelated indexes,Hcy and serum inflammatory cytokines,and risk of adverse pregnancy outcomes and complications.展开更多
BACKGROUND Insulin resistance(IR)was reported in most polycystic ovarian syndrome(PCOS)cases.Metformin,a biguanide drug,successfully reduced IR.Homeostatic Model Assessment for IR(HOMA-IR)and Doppler parameters assess...BACKGROUND Insulin resistance(IR)was reported in most polycystic ovarian syndrome(PCOS)cases.Metformin,a biguanide drug,successfully reduced IR.Homeostatic Model Assessment for IR(HOMA-IR)and Doppler parameters assessed metformin's effectiveness.AIM To verify whether the area under the curve of the internal carotid artery(AUC-ICA)Doppler wave can be a useful marker for assessing IR among PCOS cases who presented with menstrual irregularity and were treated with metformin over 6 mo.METHODS An observational,cross-sectional study recruited 54 eligible PCOS women;the anthropometrics were as follows:age,body mass index(BMI),menstrual cycle days,biochemical serum cholesterol,low and high-density lipoprotein,sex hormone-binding globulin,fasting blood glucose,and HOMA-IR,hormonal testosterone,luteinizing hormone over follicle-stimulating hormone ratio,and ultrasonic pulsatility index(PI)and resistance index(RI),carotid artery intima-media thickness(CIMT)and(AUC-ICA)parameters were initially recorded and repeated 3 mo and 6 mo later with metformin tab 500 mg;three times/day for 6 mo.In addition,AUC-ICA was assessed by taking repeated systolic and diastolic wave height measurements.RESULTS Metformin caused a progressive reduction in BMI,menstrual cycle days,biochemical hormonal,and Doppler parameters(CIMT,PI,RI,and AUC-ICA).AUC-ICA correlated strongly to all PCOS parameters.AUC-ICA correlated inversely with treatment time(r=-0.98,P<0.001)and positively with HOMA-IR(r=0.98,P<0.0001).Via the best subset regression model,the AUC-ICA had the highest predictive value for HOMA-IR.CONCLUSION AUC-ICA preceded PI,RI,and CIMT with a strong,meaningful correlation to all PCOS parameters,making it a reliable marker for the assessment of IR,especially during metformin therapy.Further studies are recommended to promote the application in practice.展开更多
Diabetes mellitus(DM)is still one of the most common diseases worldwide,and its prevalence is still increasing globally.According to the American and European recommendations,metformin is considered a first-line oral ...Diabetes mellitus(DM)is still one of the most common diseases worldwide,and its prevalence is still increasing globally.According to the American and European recommendations,metformin is considered a first-line oral hypoglycemic drug for controlling type 2 DM(T2DM)patients.Metformin is the ninth most often prescribed drug in the world,and at least 120 million diabetic people are estimated to receive the drug.In the last 20 years,there has been increasing evidence of vitamin B12 deficiency among metformin-treated diabetic patients.Many studies have reported that vitamin B12 deficiency is related to the malabsorption of vitamin B12 among metformin-treated T2DM patients.Vitamin B12 deficiency may have a very bad complication for the T2DM patient.In this review,we will focus on the effect of metformin on the absorption of vitamin B12 and on its proposed mechanisms in hindering vitamin B12 absorption.In addition,the review will describe the clinical outcomes of vitamin B12 deficiency in metformintreated T2DM.展开更多
[Objectives]This study was conducted to investigate the effects of different concentrations of cisplatin and metformin on the growth and proliferation of nasopharyngeal carcinoma SUNE-1 cells.[Methods]The concentratio...[Objectives]This study was conducted to investigate the effects of different concentrations of cisplatin and metformin on the growth and proliferation of nasopharyngeal carcinoma SUNE-1 cells.[Methods]The concentrations of cisplatin were set as 2.5,5.0,10.0,25.0,40.0μg/mL,and those of metformin were set as 0.625,1.25,2.5,5,10,and 20 mmol/L.After 48 h of intervention in nasopharyngeal carcinoma SUNE-1 cells,the proliferation inhibitory rate and the median inhibitory concentration(IC_(50))of SUNE-1 cells were measured by the CCK-8 method.[Results]It was found that different concentrations of cisplatin and metformin all had an inhibitory effect on the proliferation of SUNE-1 cells,and the inhibitory effect became more significant with the increase of concentration.The IC_(50)values of cisplatin and metformin were 43.57μg/mL and 6.855 mmol/L,respectively.[Conclusions]Cisplatin and metformin inhibited the proliferation of SUNE-1 cells in a concentration-dependent manner,providing a theoretical guidance for the clinical treatment of nasopharyngeal carcinoma.展开更多
Background: Metformin (M) is an effective first-line hypoglycemic agent in obese type 2 diabetes mellitus due to its low cost and safety profile. The Case: A 66-year-man presented with shock due to lactic acidosis ind...Background: Metformin (M) is an effective first-line hypoglycemic agent in obese type 2 diabetes mellitus due to its low cost and safety profile. The Case: A 66-year-man presented with shock due to lactic acidosis induced by M-supersaturation subsequent to acute renal failure following infective diarrhea. The drug has been used, by this patient, for >10 years without complication. Physical examination, laboratory tests, radiological investigations and blood cultures did not show evidence of new cardiac, hepatic and septic insult. Despite discontinuation of M and 2-days of aggressive hydration, bicarbonate infusions and pressors;toxic levels of the drug persisted and shock-state culminated in severe and oliguric renal failure with serum urea and creatinine up to 50 mmol/L and 1270 umol/L, respectively. Hence, continuous venovenous hemodiafiltration (CVVHDF) was used, for 16-hours, to remove the drug, correct his acidosis and support his severe renal complications. Hours after the procedure;drug level, lactic acidosis and its associated shock improved followed by gradual renal recovery. The patient was discharged after 6 days and serum creatinine reached his base line (180 umol/L) 2 weeks later. The drug was not recommended for his future use. Conclusion: M-induced lactic acidosis, should be considered in assessment of shock in M-treated patients and management of unstable patients indicates early-use of CVVHDF.展开更多
Pituitary tumors are common intracranial tumors,but when faced with drugresistant or aggressive tumors,existing medical measures may not provide good control,leading to progression and deterioration.Metformin,a tradit...Pituitary tumors are common intracranial tumors,but when faced with drugresistant or aggressive tumors,existing medical measures may not provide good control,leading to progression and deterioration.Metformin,a traditional hypoglycemic drug,has recently been discovered to have multiple functions including antitumor effects.There have been studies on the mechanism of metformin for the treatment of pituitary tumors,but it is uncertain whether it will provide new adjuvant or alternative therapies for the treatment of these tumors.We analyzed the potential mechanisms of action of metformin with respect to the inhibition of pituitary tumor growth and hormone secretion by reviewing the available literature.展开更多
Objective:To investigate the impact of combining liraglutide with metformin on the enhancement of pancreatic islet function in patients with type 2 diabetes and coronary heart disease.Methods:60 patients with type 2 d...Objective:To investigate the impact of combining liraglutide with metformin on the enhancement of pancreatic islet function in patients with type 2 diabetes and coronary heart disease.Methods:60 patients with type 2 diabetes and coronary heart disease admitted from February 2022 to August 2023 were selected as research subjects.They were randomly assigned to either control or treatment groups,with 30 patients in each.The control group received metformin alone,while the treatment group received liraglutide in combination with metformin.Various indicators,including blood sugar levels,pancreatic islet function,and cardiac function between the two groups were compared.Results:The results of FPG,2hPG,HbA1c,HOMA-IR,NT-proBNP,and LVEDD in the treatment group were lower than those in the control group,whereas the values of FINS,HOMA-β,E/A,and LVEF in the treatment group were higher than those in the control group(P<0.05).Conclusion:The use of liraglutide in combination with metformin significantly benefits patients with type 2 diabetes and coronary heart disease.It leads to improved pancreatic islet function,better blood sugar control,and enhanced cardiac function.This combination therapy is recommended for clinical adoption.展开更多
To date,metformin remains the first-line oral glucose-lowering drug used for the treatment of type 2 diabetes thanks to its well-established long-term safety and efficacy profile.Indeed,metformin is the most widely us...To date,metformin remains the first-line oral glucose-lowering drug used for the treatment of type 2 diabetes thanks to its well-established long-term safety and efficacy profile.Indeed,metformin is the most widely used oral insulinsensitizing agent,being prescribed to more than 100 million people worldwide,including patients with prediabetes,insulin resistance,and polycystic ovary syndrome.However,over the last decades several observational studies and meta-analyses have reported a significant association between long-term metformin therapy and an increased prevalence of vitamin B12 deficiency.Of note,evidence suggests that long-term and high-dose metformin therapy impairs vitamin B12 status.Vitamin B12(also referred to as cobalamin)is a water-soluble vitamin that is mainly obtained from animal-sourced foods.At the cellular level,vitamin B12 acts as a cofactor for enzymes that play a critical role in DNA synthesis and neuroprotection.Thus,vitamin B12 deficiency can lead to a number of clinical consequences that include hematologic abnormalities(e.g.,megaloblastic anemia and formation of hypersegmented neutrophils),progressive axonal demyelination and peripheral neuropathy.Nevertheless,no definite guidelines are currently available for vitamin B12 deficiency screening in patients on metformin therapy,and vitamin B12 deficiency remains frequently unrecognized in such individuals.Therefore,in this“field of vision”article we propose a list of criteria for a cost-effective vitamin B12 deficiency screening in metformin-treated patients,which could serve as a practical guide for identifying individuals at high risk for this condition.Moreover,we discuss additional relevant topics related to this field,including:(1)The lack of consensus about the exact definition of vitamin B12 deficiency;(2)The definition of reliable biomarkers of vitamin B12 status;(3)Causes of vitamin B12 deficiency other than metformin therapy that should be identified promptly in metformin-treated patients for a proper differential diagnosis;and(4)Potential pathophysiological mechanisms underlying metformin-induced vitamin B12 deficiency.Finally,we briefly review basic concepts related to vitamin B12 supplementation for the treatment of vitamin B12 deficiency,particularly when this condition is induced by metformin.展开更多
BACKGROUND Metformin is arguably the most commonly prescribed oral hypoglycemic agent for the management of diabetes.Due to the lack of randomized control trials,most of the data pertaining to the clinical course,ther...BACKGROUND Metformin is arguably the most commonly prescribed oral hypoglycemic agent for the management of diabetes.Due to the lack of randomized control trials,most of the data pertaining to the clinical course,therapeutic interventions and outcomes of patients with metformin induced toxicity has come from case reports or series.AIM To analyse the symptomology,clinical interventions and outcomes of patients presenting with severe metformin toxicity by reviewing the published case reports and series.METHODS We performed a systematic search from PubMed,Science Direct,Reference Citation Analysis(https://www.referencecitationanalysis.com/)and Google Scholar databases using the terms“metformin”AND“toxicity”OR“overdose”OR“lactic acidosis”OR“hyperlactatemia”.The inclusion criteria were:(1)Case reports or case series with individual patient details;and(2)Reported toxicity or overdose of metformin in adults,published in the English language.Data regarding baseline demographics,clinical presentation,therapeutic interventions,intensive care unit course and overall outcome were collected.RESULTS Two hundred forty-two individual cases were analysed,from 158 case reports and 26 case series,with a cumulative mortality of 19.8%.214(88.4%)patients were diabetics on metformin.57(23.6%)had acute ingestion,but a great majority(76.4%)were on metformin in therapeutic doses when they developed toxicity.Metformin associated lactic acidosis(MALA)was the most commonly reported adverse effect present in 224(92.6%)patients.Most of the patients presented with gastrointestinal and neurological symptoms and a significant number of patients had severe metabolic acidosis and hyperlactatemia.The organ support used was renal replacement therapy(RRT)(68.6%),vasopressors(58.7%)and invasive mechanical ventilation(52.9%).A majority of patients(68.6%)received RRT for toxin removal,renal dysfunction and correction of MALA.Patients with lowest pH and highest serum lactate and metformin levels also had favourable outcomes with use of RRT.CONCLUSION Most of the reported cases were on therapeutic doses of metformin but developed toxicity after an acute deterioration in renal functions.These patients may develop severe lactic acidosis,leading to significant morbidity and need for organ support.Despite severe MALA and the need for multiple organ support,they may have good outcomes,especially when RRT is used.The dose of metformin,serum pH,lactate and metformin levels may indicate the severity of toxicity and the need for aggressive therapeutic measures but may not necessarily indicate poor outcomes.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.:81973377,81903689,82073906 and 82273987)the Key Natural Science Foundation of Jiangsu Higher Education Institutions of China(Grant Nos.:19KJB350006 and 19KJA460008)+1 种基金Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),the initializing Fund of Xuzhou Medical University(Grant No.:D2018011)Postgraduate Research Practice Innovation Program of Jiangsu Province(Grant Nos.:KYCX21-2733 and KYCX22-2966).
文摘The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.
文摘BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.
文摘Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury models.Heme oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox homeostasis.Metformin is a classic drug used to treat type 2 diabetes that can inhibit ferroptosis.Previous studies have shown that,when used to treat cardiovascular and digestive system diseases,metformin can also upregulate heme oxygenase-1 expression.Therefore,we hypothesized that heme oxygenase-1 plays a significant role in mediating the beneficial effects of metformin on neuronal ferroptosis after spinal cord injury.To test this,we first performed a bioinformatics analysis based on the GEO database and found that heme oxygenase-1 was upregulated in the lesion of rats with spinal cord injury.Next,we confirmed this finding in a rat model of T9 spinal cord compression injury that exhibited spinal cord nerve cell ferroptosis.Continuous intraperitoneal injection of metformin for 14 days was found to both upregulate heme oxygenase-1 expression and reduce neuronal ferroptosis in rats with spinal cord injury.Subsequently,we used a lentivirus vector to knock down heme oxygenase-1 expression in the spinal cord,and found that this significantly reduced the effect of metformin on ferroptosis after spinal cord injury.Taken together,these findings suggest that metformin inhibits neuronal ferroptosis after spinal cord injury,and that this effect is partially dependent on upregulation of heme oxygenase-1.
文摘Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.
基金the National Institute for Medical Research Development(NIMADGrant No.995813).
文摘Intracellular communications between breast cancer and fibroblast cells were reported to be involved in cancer proliferation,growth,and therapy resitance.The hallmarks of cancer fibroblast interactions,consisting of caveolin 1(Cav1)and mono-carboxylate ransporter 4(MCT4)(metabolic coupling markers),along with IL-6,TGFB,and lactate secretion,are considered robust biomarkers predicting recurrence and metastasis.In order to promote a novel phenotype in normal fibroblasts,we predicted that breast cancer cells could be able to cause loss of Cavl and increase of MCT4,as well as elevate IL 6 and TGF in nearby nomal fibroblasts.We created a co culture model using breast cancer(4T1)and normal fibroblast(NIH3T3)cell lines cultured under specific experimental conditions in order to directly test our theory.Moreover,we show that long-term co-culture of breast cancer cells and normal fibroblasts promotes loss of Cavl and gain of MCT4 in adjacent fibroblasts and increase lactate secretion.These results were validated using the monoculture of each group separately as a control.In this system,we show that me tformin inhibits IL-6 and TGFB secretion and re expresses Cavl in both cells.However,MCT4 and lactate stayed high after treatment with metformin.In conclusion,our work shows that co-culture with breast cancer cells may cause signifcant alterations in the phenotype and secretion of normal fibroblasts.Metformin,however,may change this state and affect fibroblasts'acquired phenotypes.Moreover,mitochondrial inhibition by metformin after 8 days of treatment,signi ficantly hinders tumor growth in mouse model of breast cancer.
基金supported by the Natural Nature Science Foundation of China,Nos.82030071,81874004the Science and Technology Major Project of Changsha,No.kh2103008(all to JZH).
文摘Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury.However,its effect on spinal cord injury in aged mice remains unclear.Considering the essential role of angiogenesis during the regeneration process,we hypothesized that metformin activates the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway in endothelial cells,thereby promoting microvascular regeneration in aged mice after spinal cord injury.In this study,we established young and aged mouse models of contusive spinal cord injury using a modified Allen method.We found that aging hindered the recovery of neurological function and the formation of blood vessels in the spinal cord.Treatment with metformin promoted spinal cord microvascular endothelial cell migration and blood vessel formation in vitro.Furthermore,intraperitoneal injection of metformin in an in vivo model promoted endothelial cell proliferation and increased the density of new blood vessels in the spinal cord,thereby improving neurological function.The role of metformin was reversed by compound C,an adenosine monophosphate-activated protein kinase inhibitor,both in vivo and in vitro,suggesting that the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway likely regulates metformin-mediated angiogenesis after spinal cord injury.These findings suggest that metformin promotes vascular regeneration in the injured spinal cord by activating the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway,thereby improving the neurological function of aged mice after spinal cord injury.
基金This work was funded by the Medical and Health Science and Technology Program of Zhejiang Province(2021KY813)the National Natural Science Foundation of China(82174095)the National Natural Science Foundation of Zhejiang Province(LZ22H290001).
文摘Cancer-associated fibroblasts(CAFs)are one of the most abundant stromal cells in the tumor microenvironment which mediate desmoplastic response and are the primary driver for an immunosuppressive microenvironment,leading to the failure of triple-negative breast cancer(TNBC)immunotherapy.Therefore,depleting CAFs may enhance the effect of immunotherapy(such as PD-L1 antibody).Relaxin(RLN)has been demonstrated to significantly improve transforming growth factor-β(TGF-β)induced CAFs activation and tumor immunosuppressive microenvironment.However,the short half-life and systemic vasodilation of RLN limit its in vivo efficacy.Here,plasmid encoding relaxin(pRLN)to locally express RLN was delivered with a new positively charged polymer named polymeric metformin(PolyMet),which could increase gene transfer efficiency significantly and have low toxicity that have been certified by our lab before.In order to improve the stability of pRLN in vivo,this complex was further formed lipid poly-γ-glutamic acid(PGA)/PolyMetpRLN nanoparticle(LPPR).The particle size of LPPR was 205.5±2.9 nm,and the zeta potential was+55.4±1.6 mV.LPPR displayed excellent tumor penetrating efficacy and weaken proliferation of CAFs in 4T1luc/CAFs tumor spheres in vitro.In vivo,it could reverse aberrantly activated CAFs by decreasing the expression of profibrogenic cytokine and remove the physical barrier to reshape the tumor stromal microenvironment,which enabled a 2.2-fold increase in cytotoxic T cell infiltration within the tumor and a decrease in immunosuppressive cells infiltration.Thus,LPPR was observed retarded tumor growth by itself in the 4T1 tumor bearing-mouse,and the reshaped immune microenvironment further led to facilitate antitumor effect when it combined with PD-L1 antibody(aPD-L1).Altogether,this study presented a novel therapeutic approach against tumor stroma using LPPR to achieve a combination regimen with immune checkpoint blockade therapy against the desmoplastic TNBC model.
文摘Objective:Polycystic ovary syndrome(Pcos)is a pathophysiological disorder affecting reproductive and metabolic indices in females.The present study was designed to compare the efficacy of metformin and D-chiroinositol in PcoS patients.Methods:In a tertiary care hospital in North India,prospective observational research was undertaken on 1o0 patients with PCOS,which was diagnosed based on European Society of Human Reproduction and Embryology Guidelines and ultrasound of lower abdomen.The study involves various clinical characteristics into consideration for the determination of statistical significance(P<0.05)in PCOS patients.Student's t-test along with the association between PCOS and patients taking metformin and D-chiro-inositol,as well as their impact on various biochemical parameters,were investigated finally using Pearson Correlation Analysis.Results:This study comprises 50 patients taking metformin and 50 patients taking D-chiro-inositol in women suffering from PCOS.Body mass index(BMI)and waist-to-hip ratio(WHR)were statistically significant(P<0.05)within the groups of both metformin and D-chiro-inositol.Biochemical parameters such as luteinizing hormone(LH),follicle stimulating hormone(FSH),anti-mullerian hormone(AMH)and glycated hemoglobin(HbA1c)were found to be statistically significant(P<0.05)in both groups.LH,FSH and AMH(14.40±0.52;14.28±0.53;1.99±0.10)were comparatively lower in patients taking D-chiro-inositol as compared to metformin group(14.17±0.42;19.88±1.01;2.61±0.04).HbA1c(3.71±0.08)with P<0.05 was found to be decreased more in metformin group as compared to patients taking D-chiro-inositol(4.90±0.09).A positive correlation was found between HbAlc and LH in metformin,&HbAlc and FSH in D-chiro-inositol groups,respectively.Conclusion:The results indicate that D-chiro-inositol shows better results in reducing clinical variables involved in causing PCOS as compared to metformin whereas metformin has better glycemic control in PCOS patients.
基金supported by grants from the National Natural Science Foundation of China(Grant No.:81972811)the Key Research and Development Foundation of Shaanxi Province(Grant Nos.:2018SF-099,S2021SF-136,2021JM-273,and 2022JQ-848)+1 种基金the Fundamental Research Funds for the Central Universities(Grant No.:xzy012022094)the Provincial Science and Technology Rising Star(Grant No.:2021KJXX-03).
文摘The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed independently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endothelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.
文摘Objective:To compare the effectiveness of inositol and metformin on the clinical characteristics,and endocrine and metabolic profiles of infertile polycystic ovarian syndrome(PCOS)women from Vietnam.Methods:From June 2018 to August 2022,a randomized trial was undertaken at the Hue Center for Endocrinology and Reproduction on infertile women aged 18 to 40 years with polycystic ovarian syndrome.The clinical,endocrine,and metabolic features of these individuals were assessed before and after 3 months of treatment with 2 g of inositol or 1700 mg of metformin per day.Natural pregnancy rates,adverse effects,and tolerance of inositol were recorded.Results:The study included 171 infertile PCOS women who were eligible to participate and took part in the baseline assessment,of whom 132 women participated in data analysis after 3 months.After metformin treatment,42.1%of women with oligomenorrhea experienced regular menstruation.Metformin significantly lowered body mass index(BMI),waist circumference and testosterone levels,but had no effect on other clinical characteristics,endocrine profiles,or metabolic profiles.29.2%Of women reported experiencing side effects.21%Of them attained pregnancy,which resulted in 17.1%of live births.In the inositol group,the rate of regular cycle increased by 18.2%and the total testosterone concentration significantly decreased.In overweight/obese women with PCOS,inositol significantly decreased weight,BMI,waist and hip circumferences(P<0.05).100%Of women tolerated inositol and continued treatment.18.9%Of them became pregnant,leading to 17%of live births.Conclusions:Metformin and inositol can improve weight and waist circumference in overweight/obese infertile women with PCOS.Metformin is associated with a higher rate of regular menstruation,whereas inositol is associated with a lower rate of adverse effects.The spontaneous conception,clinical pregnancy,and live birth rates between two groups are comparable.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is among the commonest malignancies associated with significant cancer-related death.The identification of chemopreventive agents following HCC treatments with the potential to lower the risk of HCC adverse course is intriguing.Metformin,a first-line agent used in the treatment of type 2 diabetes mellitus(T2DM),has been associated with inhibition of HCC growth.AIM To determine whether metformin can prevent adverse events(i.e.,death,tumor progression,and recurrence)after any HCC treatment in T2DM patients.METHODS A systematic review of the published literature was undertaken focused on the role of metformin on outcomes in patients with T2DM and HCC receiving any tumor therapy.A search of the PubMed and Cochrane Central Register of Controlled Trials Databases was conducted.RESULTS A total of 13 studies(n=14886 patients)were included in this review.With regard to the risk of death,a decreased risk was reported in cases receiving metformin,although this decrease was not statistically significant[odds ratio(OR)=0.89,P=0.42].When only patients treated with curative strategies were considered,a more marked correlation between metformin and favorable cases was reported(OR=0.70,P=0.068).When analyzing palliative treatment,there was no statistical significance in terms of the correlation between metformin and favorable cases(OR=0.74,P=0.66).As for the risks of progressive disease and recurrence,no obvious correlation between metformin use and reduced risk was reported.When sub-analyses were performed for patients from different regions,the results for patients from Eastern countries showed a tendency for decreased risk of death in T2DM cases receiving metformin(OR=0.69,P=0.17),but the same was not seen in patients from Western countries(OR=1.19,P=0.31).CONCLUSION Metformin failed to show a marked impact in preventing adverse effects after HCC treatment.A trend was reported in T2DM cases receiving curative therapies in relation to the risk of death,especially in patients from Eastern regions.Great heterogeneity was reported among the different studies.Further large studies are required to definitively clarify the real impact of metformin as a chemopreventive agent for HCC.
文摘BACKGROUND Gestational diabetes mellitus(GDM)refers to hyperglycemia caused by insulin resistance or insufficient insulin secretion during pregnancy.Patients with GDM have a high risk of pregnancy complications,which can adversely affect both maternal and fetal health.Therefore,early diagnosis,treatment and monitoring of GDM are essential.In recent years,a new treatment scheme represented by insulin aspart combined with metformin has received increasing attention.AIM To explore the effects of insulin aspart combined with metformin on patients with GDM and inflammatory markers.METHODS From April 2020 to September 2022,124 patients with GDM in Sanya Women and Children’s Hospital Managed by Shanghai Children’s Medical Center were collected and analyzed retrospectively.The control group(CG)comprised 62 patients treated with insulin aspart alone,and 62 patients treated with insulin aspart and metformin formed the observation group(OG).Before and after treatment,improvement of blood-glucose-related indexes[fasting blood glucose(FBG),2-h postprandial glucose(2h PG)and hemoglobin A1c(HbA1c)],serum related factor[serum homocysteine(Hcy)],serum inflammatory cytokines[tumor necrosis factor(TNF)-α,interleukin(IL)-6 and C-reactive protein(CRP)]were compared between the two groups.The clinical efficacy,adverse pregnancy outcomes and incidence of pregnancy complications were compared between the two groups.RESULTS After treatment,the levels of FBG,2h PG,HbA1c,Hcy,TNF-α,IL-6 and CRP in both groups were significantly decreased(P<0.05),and the levels of FBG,2h PG,HbA1c,Hcy,TNF-α,IL-6 and CRP in the OG were lower than in the CG(P<0.05).The total clinical effectiveness in the OG was higher than that in the CG(P<0.05).The total incidence of adverse pregnancy outcomes and complications in the OG was significantly lower than in the CG(P<0.05).CONCLUSION Insulin aspart combined with metformin are effective for treatment of GDM,which can reduce blood-glucoserelated indexes,Hcy and serum inflammatory cytokines,and risk of adverse pregnancy outcomes and complications.
基金The ethical committee of Mustansiriyah University approved the study dated February/21/2019(IRB No.115).
文摘BACKGROUND Insulin resistance(IR)was reported in most polycystic ovarian syndrome(PCOS)cases.Metformin,a biguanide drug,successfully reduced IR.Homeostatic Model Assessment for IR(HOMA-IR)and Doppler parameters assessed metformin's effectiveness.AIM To verify whether the area under the curve of the internal carotid artery(AUC-ICA)Doppler wave can be a useful marker for assessing IR among PCOS cases who presented with menstrual irregularity and were treated with metformin over 6 mo.METHODS An observational,cross-sectional study recruited 54 eligible PCOS women;the anthropometrics were as follows:age,body mass index(BMI),menstrual cycle days,biochemical serum cholesterol,low and high-density lipoprotein,sex hormone-binding globulin,fasting blood glucose,and HOMA-IR,hormonal testosterone,luteinizing hormone over follicle-stimulating hormone ratio,and ultrasonic pulsatility index(PI)and resistance index(RI),carotid artery intima-media thickness(CIMT)and(AUC-ICA)parameters were initially recorded and repeated 3 mo and 6 mo later with metformin tab 500 mg;three times/day for 6 mo.In addition,AUC-ICA was assessed by taking repeated systolic and diastolic wave height measurements.RESULTS Metformin caused a progressive reduction in BMI,menstrual cycle days,biochemical hormonal,and Doppler parameters(CIMT,PI,RI,and AUC-ICA).AUC-ICA correlated strongly to all PCOS parameters.AUC-ICA correlated inversely with treatment time(r=-0.98,P<0.001)and positively with HOMA-IR(r=0.98,P<0.0001).Via the best subset regression model,the AUC-ICA had the highest predictive value for HOMA-IR.CONCLUSION AUC-ICA preceded PI,RI,and CIMT with a strong,meaningful correlation to all PCOS parameters,making it a reliable marker for the assessment of IR,especially during metformin therapy.Further studies are recommended to promote the application in practice.
文摘Diabetes mellitus(DM)is still one of the most common diseases worldwide,and its prevalence is still increasing globally.According to the American and European recommendations,metformin is considered a first-line oral hypoglycemic drug for controlling type 2 DM(T2DM)patients.Metformin is the ninth most often prescribed drug in the world,and at least 120 million diabetic people are estimated to receive the drug.In the last 20 years,there has been increasing evidence of vitamin B12 deficiency among metformin-treated diabetic patients.Many studies have reported that vitamin B12 deficiency is related to the malabsorption of vitamin B12 among metformin-treated T2DM patients.Vitamin B12 deficiency may have a very bad complication for the T2DM patient.In this review,we will focus on the effect of metformin on the absorption of vitamin B12 and on its proposed mechanisms in hindering vitamin B12 absorption.In addition,the review will describe the clinical outcomes of vitamin B12 deficiency in metformintreated T2DM.
基金Supported by Fujian Provincial Young and Middle-aged Teacher Education and Scientific Research Project(JAT200706)Innovation and Entrepreneurship Training Program for College Students of Xiamen Medical College(X202112631068)。
文摘[Objectives]This study was conducted to investigate the effects of different concentrations of cisplatin and metformin on the growth and proliferation of nasopharyngeal carcinoma SUNE-1 cells.[Methods]The concentrations of cisplatin were set as 2.5,5.0,10.0,25.0,40.0μg/mL,and those of metformin were set as 0.625,1.25,2.5,5,10,and 20 mmol/L.After 48 h of intervention in nasopharyngeal carcinoma SUNE-1 cells,the proliferation inhibitory rate and the median inhibitory concentration(IC_(50))of SUNE-1 cells were measured by the CCK-8 method.[Results]It was found that different concentrations of cisplatin and metformin all had an inhibitory effect on the proliferation of SUNE-1 cells,and the inhibitory effect became more significant with the increase of concentration.The IC_(50)values of cisplatin and metformin were 43.57μg/mL and 6.855 mmol/L,respectively.[Conclusions]Cisplatin and metformin inhibited the proliferation of SUNE-1 cells in a concentration-dependent manner,providing a theoretical guidance for the clinical treatment of nasopharyngeal carcinoma.
文摘Background: Metformin (M) is an effective first-line hypoglycemic agent in obese type 2 diabetes mellitus due to its low cost and safety profile. The Case: A 66-year-man presented with shock due to lactic acidosis induced by M-supersaturation subsequent to acute renal failure following infective diarrhea. The drug has been used, by this patient, for >10 years without complication. Physical examination, laboratory tests, radiological investigations and blood cultures did not show evidence of new cardiac, hepatic and septic insult. Despite discontinuation of M and 2-days of aggressive hydration, bicarbonate infusions and pressors;toxic levels of the drug persisted and shock-state culminated in severe and oliguric renal failure with serum urea and creatinine up to 50 mmol/L and 1270 umol/L, respectively. Hence, continuous venovenous hemodiafiltration (CVVHDF) was used, for 16-hours, to remove the drug, correct his acidosis and support his severe renal complications. Hours after the procedure;drug level, lactic acidosis and its associated shock improved followed by gradual renal recovery. The patient was discharged after 6 days and serum creatinine reached his base line (180 umol/L) 2 weeks later. The drug was not recommended for his future use. Conclusion: M-induced lactic acidosis, should be considered in assessment of shock in M-treated patients and management of unstable patients indicates early-use of CVVHDF.
基金Supported by the Science and Technology Program of Nantong Health Committee,No.MA2019003,No.MA2021017,No.Key003Science and Technology Program of Nantong City,NO.MS12015016,and No.JCZ2022040and Kangda College of Nanjing Medical University,No.KD2021JYYJYB025,No.KD2022KYJJZD019,and No.KD2022KJJZZD022.
文摘Pituitary tumors are common intracranial tumors,but when faced with drugresistant or aggressive tumors,existing medical measures may not provide good control,leading to progression and deterioration.Metformin,a traditional hypoglycemic drug,has recently been discovered to have multiple functions including antitumor effects.There have been studies on the mechanism of metformin for the treatment of pituitary tumors,but it is uncertain whether it will provide new adjuvant or alternative therapies for the treatment of these tumors.We analyzed the potential mechanisms of action of metformin with respect to the inhibition of pituitary tumor growth and hormone secretion by reviewing the available literature.
文摘Objective:To investigate the impact of combining liraglutide with metformin on the enhancement of pancreatic islet function in patients with type 2 diabetes and coronary heart disease.Methods:60 patients with type 2 diabetes and coronary heart disease admitted from February 2022 to August 2023 were selected as research subjects.They were randomly assigned to either control or treatment groups,with 30 patients in each.The control group received metformin alone,while the treatment group received liraglutide in combination with metformin.Various indicators,including blood sugar levels,pancreatic islet function,and cardiac function between the two groups were compared.Results:The results of FPG,2hPG,HbA1c,HOMA-IR,NT-proBNP,and LVEDD in the treatment group were lower than those in the control group,whereas the values of FINS,HOMA-β,E/A,and LVEF in the treatment group were higher than those in the control group(P<0.05).Conclusion:The use of liraglutide in combination with metformin significantly benefits patients with type 2 diabetes and coronary heart disease.It leads to improved pancreatic islet function,better blood sugar control,and enhanced cardiac function.This combination therapy is recommended for clinical adoption.
文摘To date,metformin remains the first-line oral glucose-lowering drug used for the treatment of type 2 diabetes thanks to its well-established long-term safety and efficacy profile.Indeed,metformin is the most widely used oral insulinsensitizing agent,being prescribed to more than 100 million people worldwide,including patients with prediabetes,insulin resistance,and polycystic ovary syndrome.However,over the last decades several observational studies and meta-analyses have reported a significant association between long-term metformin therapy and an increased prevalence of vitamin B12 deficiency.Of note,evidence suggests that long-term and high-dose metformin therapy impairs vitamin B12 status.Vitamin B12(also referred to as cobalamin)is a water-soluble vitamin that is mainly obtained from animal-sourced foods.At the cellular level,vitamin B12 acts as a cofactor for enzymes that play a critical role in DNA synthesis and neuroprotection.Thus,vitamin B12 deficiency can lead to a number of clinical consequences that include hematologic abnormalities(e.g.,megaloblastic anemia and formation of hypersegmented neutrophils),progressive axonal demyelination and peripheral neuropathy.Nevertheless,no definite guidelines are currently available for vitamin B12 deficiency screening in patients on metformin therapy,and vitamin B12 deficiency remains frequently unrecognized in such individuals.Therefore,in this“field of vision”article we propose a list of criteria for a cost-effective vitamin B12 deficiency screening in metformin-treated patients,which could serve as a practical guide for identifying individuals at high risk for this condition.Moreover,we discuss additional relevant topics related to this field,including:(1)The lack of consensus about the exact definition of vitamin B12 deficiency;(2)The definition of reliable biomarkers of vitamin B12 status;(3)Causes of vitamin B12 deficiency other than metformin therapy that should be identified promptly in metformin-treated patients for a proper differential diagnosis;and(4)Potential pathophysiological mechanisms underlying metformin-induced vitamin B12 deficiency.Finally,we briefly review basic concepts related to vitamin B12 supplementation for the treatment of vitamin B12 deficiency,particularly when this condition is induced by metformin.
文摘BACKGROUND Metformin is arguably the most commonly prescribed oral hypoglycemic agent for the management of diabetes.Due to the lack of randomized control trials,most of the data pertaining to the clinical course,therapeutic interventions and outcomes of patients with metformin induced toxicity has come from case reports or series.AIM To analyse the symptomology,clinical interventions and outcomes of patients presenting with severe metformin toxicity by reviewing the published case reports and series.METHODS We performed a systematic search from PubMed,Science Direct,Reference Citation Analysis(https://www.referencecitationanalysis.com/)and Google Scholar databases using the terms“metformin”AND“toxicity”OR“overdose”OR“lactic acidosis”OR“hyperlactatemia”.The inclusion criteria were:(1)Case reports or case series with individual patient details;and(2)Reported toxicity or overdose of metformin in adults,published in the English language.Data regarding baseline demographics,clinical presentation,therapeutic interventions,intensive care unit course and overall outcome were collected.RESULTS Two hundred forty-two individual cases were analysed,from 158 case reports and 26 case series,with a cumulative mortality of 19.8%.214(88.4%)patients were diabetics on metformin.57(23.6%)had acute ingestion,but a great majority(76.4%)were on metformin in therapeutic doses when they developed toxicity.Metformin associated lactic acidosis(MALA)was the most commonly reported adverse effect present in 224(92.6%)patients.Most of the patients presented with gastrointestinal and neurological symptoms and a significant number of patients had severe metabolic acidosis and hyperlactatemia.The organ support used was renal replacement therapy(RRT)(68.6%),vasopressors(58.7%)and invasive mechanical ventilation(52.9%).A majority of patients(68.6%)received RRT for toxin removal,renal dysfunction and correction of MALA.Patients with lowest pH and highest serum lactate and metformin levels also had favourable outcomes with use of RRT.CONCLUSION Most of the reported cases were on therapeutic doses of metformin but developed toxicity after an acute deterioration in renal functions.These patients may develop severe lactic acidosis,leading to significant morbidity and need for organ support.Despite severe MALA and the need for multiple organ support,they may have good outcomes,especially when RRT is used.The dose of metformin,serum pH,lactate and metformin levels may indicate the severity of toxicity and the need for aggressive therapeutic measures but may not necessarily indicate poor outcomes.
