BACKGROUND Hospice care plays an important role in improving the quality of life of advanced cancer patients,but controversy remains over whether age affects the attitudes of family members toward hospice care.AIM To ...BACKGROUND Hospice care plays an important role in improving the quality of life of advanced cancer patients,but controversy remains over whether age affects the attitudes of family members toward hospice care.AIM To investigate the attitudes of family members of advanced cancer patients of different ages toward hospice care.METHODS The study participants were 175 family members of patients with advanced cancer from January 2020 and October 2022.The participants were divided into youth(<40 years,n=65),middle-aged(40–60 years,n=59),and elderly(>60 years,n=51)groups.Researchers investigated and compared the degree of awareness regarding hospice care,attitudes,and whether the family members of patients would choose hospice care.RESULTS Among the family members of 175 patients,approximately 28%(49/175)were aware of hospice care.Awareness of hospice care,the proportion of hospice care acceptance and adaptation attitudes,and the proportion of those who chose hospice care in the youth group were higher in the middle-aged and elderly groups(P<0.05).No statistically significant difference was found in these three indicators between the middle-aged and elderly groups(P>0.05).Hospice care was chosen mainly to relieve pain and reduce unnecessary treatment,whereas the reasons for not choosing hospice care were mainly distrust and ethical concerns.CONCLUSION The family members of patients with advanced cancer had relatively low awareness of hospice care,while youth had a higher awareness of hospice care,acceptance,and adaptation attitudes,and were more willing to choose hospice care.展开更多
Objective: To investigate the associated collateral stigma of the family members of schizophrenia patients and analyze its current status and influencing factors. Methods: The Link Depreciation-Discrimination Percepti...Objective: To investigate the associated collateral stigma of the family members of schizophrenia patients and analyze its current status and influencing factors. Methods: The Link Depreciation-Discrimination Perception Scale was used to investigate the status quo of the associated stigma of the family members of 169 schizophrenia patients diagnosed in 4 hospitals in a certain province. The results of the investigation were analyzed and summarized. Results: The detection rate of stigma associated with the family members of schizophrenia patients was 72.78%, with a score of 28.41 ± 3.92 points. The main influencing factors were the family member’s education level, the patient’s illness duration, the family member’s occupation, and the family-patient relationship. Conclusion: The detection rate of stigma associated with schizophrenia was relatively high. This requires increased attention and appropriate nursing intervention.展开更多
Carboxyl terminus of Hsp70-interacting protein（CHIP or STUB1） is an E3 ligase and regulates the stability of several proteins which are involved in different cellular functions. Our previous studies demonstrated tha...Carboxyl terminus of Hsp70-interacting protein（CHIP or STUB1） is an E3 ligase and regulates the stability of several proteins which are involved in different cellular functions. Our previous studies demonstrated that Chip deficient mice display bone loss phenotype due to increased osteoclast formation through enhancing TRAF6 activity in osteoclasts. In this study we provide novel evidence about the function of CHIP. We found that osteoblast differentiation and bone formation were also decreased in Chip KO mice. In bone marrow stromal（BMS） cells derived from Chip^-/- mice, expression of a panel of osteoblast marker genes was significantly decreased. ALP activity and mineralized bone matrix formation were also reduced in Chip-deficient BMS cells. We also found that in addition to the regulation of TRAF6, CHIP also inhibits TNFα-induced NF-κB signaling through promoting TRAF2 and TRAF5 degradation. Specific deletion of Chip in BMS cells downregulated expression of osteoblast marker genes which could be reversed by the addition of NF-κB inhibitor. These results demonstrate that the osteopenic phenotype observed in Chip^-/- mice was due to the combination of increased osteoclast formation and decreased osteoblast differentiation. Taken together, our findings indicate a significant role of CHIP in bone remodeling.展开更多
Carotenoids are important nutrients for human health that must be obtained from plants since they cannot be biosynthesized by the human body.Dissecting the regulatory mechanism of carotenoid metabolism in plants repre...Carotenoids are important nutrients for human health that must be obtained from plants since they cannot be biosynthesized by the human body.Dissecting the regulatory mechanism of carotenoid metabolism in plants represents the first step toward manipulating carotenoid contents in plants by molecular design breeding.In this study,we determined that SlAP2c,an APETALA2(AP2)family member,acts as a transcriptional repressor to regulate carotenoid biosynthesis in tomato(Solanum lycopersicum).Knockout of SlAP2c in both the“Micro Tom”and“Ailsa Craig”backgrounds resulted in greater lycopene accumulation,whereas overexpression of this gene led to orange-ripe fruit with significantly lower lycopene contents than the wild type.We established that SlAP2c represses the expression of genes involved in lycopene biosynthesis by directly binding to the cis-elements in their promoters.Moreover,SlAP2c relies on its EAR motif to recruit the co-repressors TOPLESS(TPL)2/4 and forms a complex with histone deacetylase(had)1/3,thereby reducing the histone acetylation levels of lycopene biosynthesis genes.Furthermore,SlAP2a,a homolog of SlAP2c,acts upstream of SlAP2c and alleviates the SlAP2c-induced repression of lycopene biosynthesis genes by inhibiting SlAP2c transcription during fruit ripening.Therefore,we identified a transcriptional cascade mediated by AP2 family members that regulates lycopene biosynthesis during fruit ripening in tomato,laying the foundation for the manipulation of carotenoid metabolism in plants.展开更多
Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chem...Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.展开更多
BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has sho...BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.展开更多
Genome sequencing has revealed frequent mutations in Ras homolog family member A(RHOA)among various cancers with unique aberrant profiles and pathogenic effects,especially in peripheral T-cell lymphoma(PTCL).The discr...Genome sequencing has revealed frequent mutations in Ras homolog family member A(RHOA)among various cancers with unique aberrant profiles and pathogenic effects,especially in peripheral T-cell lymphoma(PTCL).The discrete positional distribution and types of RHOA amino acid substitutions vary according to the tumor type,thereby leading to different functional and biological properties,which provide new insight into the molecular pathogenesis and potential targeted therapies for various tumors.However,the similarities and discrepancies in characteristics of RHOA mutations among various histologic subtypes of PTCL have not been fully elucidated.Herein we highlight the inconsistencies and complexities of the type and location of RHOA mutations and demonstrate the contribution of RHOA variants to the pathogenesis of PTCL by combining epigenetic abnormalities and activating multiple downstream pathways.The promising potential of targeting RHOA as a therapeutic modality is also outlined.This review provides new insight in the field of personalized medicine to improve the clinical outcomes for patients.展开更多
Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways...Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle function.The process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle function.Muscle contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular junction.Within muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate force.Regulation of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction coupling.The development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as myogenesis.Myogenic regulators coordinate the diffe rentiation of myoblasts into mature muscle fibers.Signaling pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient availability.Seve ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal muscle.Therapeutic interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular pathways.Other molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling pathway.In recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular junction.In fact,research in the last few years now suggests that these two signaling pathways are interconnected and that they jointly control physiological and pathophysiological processes in muscle fibers.In this review,we will summarize and discuss the data on these two pathways,focusing on their concerted action next to their contribution to skeletal muscle biology.However,an in-depth discussion of the noncanonical Wnt pathway,the fibro/a dipogenic precursors,or the mechanosensory aspects of these pathways is not the focus of this review.展开更多
BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC...BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.展开更多
Objective To evaluate the mental health status of family members of patients with schizophrenia in China.Methods Wan Fang,CNKI,VIP,CBM,Springer Link,Science Direct and Pub Med databases were searched to collect the re...Objective To evaluate the mental health status of family members of patients with schizophrenia in China.Methods Wan Fang,CNKI,VIP,CBM,Springer Link,Science Direct and Pub Med databases were searched to collect the relevant studies published prior to August 2016 that were about the psychological health status of the family members of patients with schizophrenia measured with the SCL-90 scale and Software Stata 11.0 was used for their meta-analysis.Results A total of 20 studies was included in this meta-analysis.Scores of somatization affection,obsessive-compulsive symptoms,interpersonal sensitivity,depression,anxiety,hostility,phobic anxiety,and paranoia ideation of the family members were significantly higher than those of general population norms in 2006(P<0.05).Scores of somatization affection,interpersonal sensitivity,depression,anxiety,hostility,phobic anxiety,paranoia ideation,and psychoticism of the family members were significantly higher than control group(P<0.05).Moreover,the difference was not statistically significant between male and female family members in mental health status(P>0.05).Conclusion Compared with the general population,psychological distress was more reported in the family members of patients with schizophrenia.There was no statistic significantly difference between male and female members.展开更多
BACKGROUND Metabolic reprogramming has been identified as a core hallmark of cancer.Solute carrier family 2 is a major glucose carrier family.It consists of 14 members,and we mainly study solute carrier family 2 membe...BACKGROUND Metabolic reprogramming has been identified as a core hallmark of cancer.Solute carrier family 2 is a major glucose carrier family.It consists of 14 members,and we mainly study solute carrier family 2 member 1(SLC2A1)and solute carrier family 2 member 2(SLC2A2)here.SLC2A1,mainly existing in human erythrocytes,brain endothelial cells,and normal placenta,was found to be increased in hepatocellular carcinoma(HCC),while SLC2A2,the major transporter of the normal liver,was decreased in HCC.AIM To identify if SLC2A1 and SLC2A2 were associated with immune infiltration in addition to participating in the metabolic reprogramming in HCC.METHODS The expression levels of SLC2A1 and SLC2A2 were tested in HepG2 cells,HepG215 cells,and multiple databases.The clinical characteristics and survival data of SLC2A1 and SLC2A2 were examined by multiple databases.The correlation between SLC2A1 and SLC2A2 was analyzed by multiple databases.The functions and pathways in which SLC2A1,SLC2A2,and frequently altered neighbor genes were involved were discussed in String.Immune infiltration levels and immune marker genes associated with SLC2A1 and SLC2A2 were discussed from multiple databases.RESULTS The expression level of SLC2A1 was up-regulated,but the expression level of SLC2A2 was down-regulated in HepG2 cells,HepG215 cells,and liver cancer patients.The expression levels of SLC2A1 and SLC2A2 were related to tumor volume,grade,and stage in HCC.Interestingly,the expression levels of SLC2A1 and SLC2A2 were negatively correlated.Further,high SLC2A1 expression and low SLC2A2 expression were linked to poor overall survival and relapse-free survival.SLC2A1,SLC2A2,and frequently altered neighbor genes played a major role in the occurrence and development of tumors.Notably,SLC2A1 was positively correlated with tumor immune infiltration,while SLC2A2 was negatively correlated with tumor immune infiltration.Particularly,SLC2A2 methylation was positively correlated with lymphocytes.CONCLUSION SLC2A1 and SLC2A2 are independent therapeutic targets for HCC,and they are quintessential marker molecules for predicting and regulating the number and status of immune cells in HCC.展开更多
Cytokines play pleiotropic roles in human health and disease by regulating both innate and adaptive immune responses.Interleukins(ILs),a large group of cytokines,can be divided into seven families,including IL-1,IL-2,...Cytokines play pleiotropic roles in human health and disease by regulating both innate and adaptive immune responses.Interleukins(ILs),a large group of cytokines,can be divided into seven families,including IL-1,IL-2,IL-6,IL-8,IL-10,IL-12,and IL-17 families.Here,we review the functions of ILs in the pathogenesis and resolution of liver diseases,such as liver inflammation(e.g.,IL-35),alcoholrelated liver disease(e.g.,IL-11),non-alcoholic steatohepatitis(e.g.,IL-22),liver fibrosis(e.g.,Il-17a),and liver cancer(e.g.,IL-8).Overall,IL-1 family members are implicated in liver inflammation induced by different etiologies,such as alcohol consumption,high-fat diet,and hepatitis viruses.IL-2 family members mainly regulate T lymphocyte and NK cell proliferation and activation,and the differentiation of T cells.IL-6 family cytokines play important roles in acute phase response in liver infection,liver regeneration,and metabolic regulation,as well as lymphocyte activation.IL-8,also known as CXCL8,is activated in chronic liver diseases,which is associated with the accumulation of neutrophils and macrophages.IL-10 family members contribute key roles to liver immune tolerance and immunosuppression in liver disease.IL-12 family cytokines influence T-cell differentiation and play an essential role in autoimmune liver disease.IL-17 subfamilies contribute to infection defense,liver inflammation,and Th17 cell differentiation.ILs interact with different type I and type II cytokine receptors to regulate intracellular signaling pathways that mediate their functions.However,most clinical studies are only performed to evaluate IL-mediated therapies on alcohol and hepatitis virus infection-induced hepatitis.More pre-clinical and clinical studies are required to evaluate IL-mediated monotherapy and synergistic therapies.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
Chikungunya fever(CF)is caused by an arbovirus whose manifestations are extremely diverse,and it has evolved with significant severity in recent years.The clinical signs triggered by the Chikungunya virus are similar ...Chikungunya fever(CF)is caused by an arbovirus whose manifestations are extremely diverse,and it has evolved with significant severity in recent years.The clinical signs triggered by the Chikungunya virus are similar to those of other arboviruses.Generally,fever starts abruptly and reaches high levels,followed by severe polyarthralgia and myalgia,as well as an erythematous or petechial maculopapular rash,varying in severity and extent.Around 40%to 60%of affected individuals report persistent arthralgia,which can last from months to years.The symptoms of CF mainly represent the tissue tropism of the virus rather than the immunopathogenesis triggered by the host's immune system.The main mechanisms associated with arthralgia have been linked to an increase in T helper type 17 cells and a consequent increase in receptor activator of nuclear factor kappa-Βligand and bone resorption.This review suggests that persistent arthralgia results from the presence of viral antigens post-infection and the constant activation of signaling lymphocytic activation molecule family member 7 in synovial macrophages,leading to local infiltration of CD4+T cells,which sustains the inflammatory process in the joints through the secretion of pro-inflammatory cytokines.The term"long chikungunya"was used in this review to refer to persistent arthralgia since,due to its manifestation over long periods after the end of the viral infection,this clinical condition seems to be characterized more as a sequel than as a symptom,given that there is no active infection involved.展开更多
Objective:Here we evaluated the impact of varying severity of traumatic brain injury on the psychological state and demands of family caregivers.Further,we determined the most significant and least significant daily n...Objective:Here we evaluated the impact of varying severity of traumatic brain injury on the psychological state and demands of family caregivers.Further,we determined the most significant and least significant daily needs among family caregivers.Methods:We performed a cross-sectional descriptive study in three public hospitals in Tai'an,China.Three hundred caregivers related to traumatic brain injury victims were randomly selected.Patients had varying degrees of injuries(mild to severe).The Symptom Checklist-90(SCL-90)was used to assess family caregivers'psychological statuses.The Critical Care Family Needs Inventory(CCFNI)was used to determine family caregivers'needs.Finally,the Glasgow Coma Scale(GCS)was employed to define patients'level of traumatic brain injury.Results:SCL-90 scores for each psychological dimension were significantly higher with increasing TBI severity(p<0.05).Similarly,CCFNI scores were significantly higher with increasing TBI severity(p<0.05)for information,reassurance,and accessibility.These same dimensions were found to be the most important needs for family members of TBI injury victims,while support and comfort were the least important dimensions.Conclusions:The more severe pathogenic condition of the patient,the heavier the psychological pressure is on their family member caregivers.Medical staff should therefore pay close attention to the psychological health of family caregivers of TBI patients,especially family caregivers of critical cases.Interventions should be accordingly designed and conducted to meet the needs of family caregivers.展开更多
BACKGROUND Drugs targeting mitochondria can induce mitophagy and restrain proliferation in colorectal cancer(CRC)cells.Phosphoglycerate mutase family member 5(PGAM5)activates serine/threonine PTEN-induced putative kin...BACKGROUND Drugs targeting mitochondria can induce mitophagy and restrain proliferation in colorectal cancer(CRC)cells.Phosphoglycerate mutase family member 5(PGAM5)activates serine/threonine PTEN-induced putative kinase 1/Parkin pathway-mediated mitophagy.However,there are few studies on the clinical and prognostic significance of expression of PGAM5 protein and mitophagy-related protein Parkin in patients.AIM To assess the clinical significance of PGAM5 and Parkin proteins,as biomarkers for diagnosis and prognosis of CRC,by studying their expression in advanced CRC tissues and their association with clinicopathological parameters.METHODS The expression of PGAM5 and Parkin in CRC tissues from 100 patients was determined by immunohistochemistry.Each case was evaluated by using a combined scoring method based on signal intensity staining(scored 0-3)and the proportion of positively stained cancer cells(scored 0-4).The final staining score was calculated as the intensity score multiplied by the proportion score.Specimens were categorized as either high or low expression according to the Youden index,and the association between the expression of PGAM5 or Parkin and clinicopathological factors was ascertained.Additionally,we employed western blot to measure PGAM5 and Parkin protein expression in six matched pairs of CRC and adjacent non-tumor tissues.RESULTS Immunohistochemical and western blot findings showed that both PGAM5 and Parkin protein expression in tumor tissues was significantly higher than that in the adjacent tissues:PGAM5 and Parkin were mainly expressed in the cytoplasm of colonic epithelial cells.PGAM5 and Parkin protein levels were significantly positively correlated in advanced CRC tissues.Moreover,reduced Parkin protein expression was an independent prognostic factor for overall survival and progression-free survival in CRC patients as evinced by multivariate analysis.CONCLUSION The expression of PGAM5 protein and mitophagy-related protein Parkin has diagnostic significance for CRC and may become new biomarkers.Parkin may be a potential marker for the survival of CRC patients.展开更多
BACKGROUND 17α-Hydroxylase deficiency(17-OHD)is a rare form of congenital adrenal hyperplasia,characterized by hypertension,hypokalemia,and gonadal dysplasia.However,due to the lack of a comprehensive understanding o...BACKGROUND 17α-Hydroxylase deficiency(17-OHD)is a rare form of congenital adrenal hyperplasia,characterized by hypertension,hypokalemia,and gonadal dysplasia.However,due to the lack of a comprehensive understanding of this disease,it is prone to misdiagnosis and missed diagnosis,and there is no complete cure.CASE SUMMARY We report a female patient with 17-OHD.The patient was admitted to the Department of Neurology of our hospital due to limb weakness.During treatment,it was found that the patient’s condition was difficult to correct except for hypokalemia,and her blood pressure was difficult to control with various antihypertensive drugs.She was then transferred to our department for further treatment.On physical examination,the patient's gonadal development was found to be abnormal,and chromosome analysis demonstrated karyotype 46,XY.Considering the possibility of 17-OHD,the cytochrome P450 family 17 subfamily A member 1(CYP17A1)test was performed to confirm the diagnosis.CONCLUSION The clinical manifestations of 17-OHD are complex.Hormone determination,imaging examination,chromosome determination and CYP17A1 gene test are helpful for early diagnosis.展开更多
Increasing evidence indicates that aberrant expressions of some microRNAs are associated with cancer progression.However,the roles and biological mechanisms of miRNA-16-5p in human non-small cell lung cancer(NSCLC)are...Increasing evidence indicates that aberrant expressions of some microRNAs are associated with cancer progression.However,the roles and biological mechanisms of miRNA-16-5p in human non-small cell lung cancer(NSCLC)are not to be well studied.Here,we validated that the expression of miR-16-5p was decreased significantly in NSCLC samples and cell lines.The correlation between the clinicopathological features of NSCLC and the miR-16-5p expression showed that the expression of miR-16-5p in non-small cell lung cancer was linked with the advanced TNM stage,positive lymph node metastasis,with short overall survival(OS).Also,a negative correlation between miR-16-5p and Fermitin family member 2(FERMT2)was observed,implying there may be a potential link about their regulation.The hypothesis was further confirmed by in-silico analysis and dual-luciferase reporter assay.Moreover,we demonstrated that the transfections of miR-16-5p mimics could alter some biological characteristics of NSCLC cells remarkably accomplished by the expression variance of FERMT2 in vitro and in vivo assays.Summarily,this study demonstrated that miR-16-5p,as a tumor suppression factor in NSCLC by targeting FERMT2,could serve as one promising biomarker in the prediction for NSCLC patients.展开更多
文摘BACKGROUND Hospice care plays an important role in improving the quality of life of advanced cancer patients,but controversy remains over whether age affects the attitudes of family members toward hospice care.AIM To investigate the attitudes of family members of advanced cancer patients of different ages toward hospice care.METHODS The study participants were 175 family members of patients with advanced cancer from January 2020 and October 2022.The participants were divided into youth(<40 years,n=65),middle-aged(40–60 years,n=59),and elderly(>60 years,n=51)groups.Researchers investigated and compared the degree of awareness regarding hospice care,attitudes,and whether the family members of patients would choose hospice care.RESULTS Among the family members of 175 patients,approximately 28%(49/175)were aware of hospice care.Awareness of hospice care,the proportion of hospice care acceptance and adaptation attitudes,and the proportion of those who chose hospice care in the youth group were higher in the middle-aged and elderly groups(P<0.05).No statistically significant difference was found in these three indicators between the middle-aged and elderly groups(P>0.05).Hospice care was chosen mainly to relieve pain and reduce unnecessary treatment,whereas the reasons for not choosing hospice care were mainly distrust and ethical concerns.CONCLUSION The family members of patients with advanced cancer had relatively low awareness of hospice care,while youth had a higher awareness of hospice care,acceptance,and adaptation attitudes,and were more willing to choose hospice care.
文摘Objective: To investigate the associated collateral stigma of the family members of schizophrenia patients and analyze its current status and influencing factors. Methods: The Link Depreciation-Discrimination Perception Scale was used to investigate the status quo of the associated stigma of the family members of 169 schizophrenia patients diagnosed in 4 hospitals in a certain province. The results of the investigation were analyzed and summarized. Results: The detection rate of stigma associated with the family members of schizophrenia patients was 72.78%, with a score of 28.41 ± 3.92 points. The main influencing factors were the family member’s education level, the patient’s illness duration, the family member’s occupation, and the family-patient relationship. Conclusion: The detection rate of stigma associated with schizophrenia was relatively high. This requires increased attention and appropriate nursing intervention.
基金supported by National Institutes of Health Grants, R01 AR054465, R01 AR070222, and R01 AR070222supported by the grants of Natural Science Foundation of China (NSFC) to TW (grants No. 81301531 and 81572104)+1 种基金supported by the grant from Shenzhen Science and Technology Innovation Committee, China (grant No. JCYJ20160331114205502)the grant from Shenzhen Development and Reform Committee, China for Shenzhen Engineering Laboratory of Orthopedic Regenerative Technologies
文摘Carboxyl terminus of Hsp70-interacting protein（CHIP or STUB1） is an E3 ligase and regulates the stability of several proteins which are involved in different cellular functions. Our previous studies demonstrated that Chip deficient mice display bone loss phenotype due to increased osteoclast formation through enhancing TRAF6 activity in osteoclasts. In this study we provide novel evidence about the function of CHIP. We found that osteoblast differentiation and bone formation were also decreased in Chip KO mice. In bone marrow stromal（BMS） cells derived from Chip^-/- mice, expression of a panel of osteoblast marker genes was significantly decreased. ALP activity and mineralized bone matrix formation were also reduced in Chip-deficient BMS cells. We also found that in addition to the regulation of TRAF6, CHIP also inhibits TNFα-induced NF-κB signaling through promoting TRAF2 and TRAF5 degradation. Specific deletion of Chip in BMS cells downregulated expression of osteoblast marker genes which could be reversed by the addition of NF-κB inhibitor. These results demonstrate that the osteopenic phenotype observed in Chip^-/- mice was due to the combination of increased osteoclast formation and decreased osteoblast differentiation. Taken together, our findings indicate a significant role of CHIP in bone remodeling.
基金supported in part by the National Natural Science Foundation of China(no.32372780,no.32172643)the Applied Basic Research Category of Science and Technology Program of Sichuan Province(2021YFQ0071,2022YFSY0059-1,2021YFYZ00105-LH)+2 种基金the Technology Innovation and Application Development Program of Chongqing(cstc2021jscx-cylh X0001)the Natural Science Foundation of Sichuan Province,China(2023NSFSC1991)the Institutional Research Funding of Sichuan University(2022SCUNL105)。
文摘Carotenoids are important nutrients for human health that must be obtained from plants since they cannot be biosynthesized by the human body.Dissecting the regulatory mechanism of carotenoid metabolism in plants represents the first step toward manipulating carotenoid contents in plants by molecular design breeding.In this study,we determined that SlAP2c,an APETALA2(AP2)family member,acts as a transcriptional repressor to regulate carotenoid biosynthesis in tomato(Solanum lycopersicum).Knockout of SlAP2c in both the“Micro Tom”and“Ailsa Craig”backgrounds resulted in greater lycopene accumulation,whereas overexpression of this gene led to orange-ripe fruit with significantly lower lycopene contents than the wild type.We established that SlAP2c represses the expression of genes involved in lycopene biosynthesis by directly binding to the cis-elements in their promoters.Moreover,SlAP2c relies on its EAR motif to recruit the co-repressors TOPLESS(TPL)2/4 and forms a complex with histone deacetylase(had)1/3,thereby reducing the histone acetylation levels of lycopene biosynthesis genes.Furthermore,SlAP2a,a homolog of SlAP2c,acts upstream of SlAP2c and alleviates the SlAP2c-induced repression of lycopene biosynthesis genes by inhibiting SlAP2c transcription during fruit ripening.Therefore,we identified a transcriptional cascade mediated by AP2 family members that regulates lycopene biosynthesis during fruit ripening in tomato,laying the foundation for the manipulation of carotenoid metabolism in plants.
基金National Yang Ming Chiao Tung University Far Eastern Memorial Hospital Joint Research Programs(NYCU-FEMH 109DN03,110DN06,111DN04,112DN05).
文摘Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.
基金Supported by 2020 Guangxi Zhuang Autonomous Region Health Care Commission Self-Financing Research Projects,No.Z202000962023 Guangxi University Young and Middle-Aged Teachers’Basic Research Ability Improvement Project,No.2023KY0091+1 种基金National Natural Science Foundation of China,No.82260241the Natural Science Foundation of Guangxi Province,No.2015GXNSFAA139171 and No.2020GXNSFAA259053.
文摘BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.
基金This work was supported by the Natural Science Foundation of Guangdong Province(Grant No.2019A1515011354).
文摘Genome sequencing has revealed frequent mutations in Ras homolog family member A(RHOA)among various cancers with unique aberrant profiles and pathogenic effects,especially in peripheral T-cell lymphoma(PTCL).The discrete positional distribution and types of RHOA amino acid substitutions vary according to the tumor type,thereby leading to different functional and biological properties,which provide new insight into the molecular pathogenesis and potential targeted therapies for various tumors.However,the similarities and discrepancies in characteristics of RHOA mutations among various histologic subtypes of PTCL have not been fully elucidated.Herein we highlight the inconsistencies and complexities of the type and location of RHOA mutations and demonstrate the contribution of RHOA variants to the pathogenesis of PTCL by combining epigenetic abnormalities and activating multiple downstream pathways.The promising potential of targeting RHOA as a therapeutic modality is also outlined.This review provides new insight in the field of personalized medicine to improve the clinical outcomes for patients.
基金supported by the German Research Council(Deutsche Forschungsgemeinschaft,HA3309/3-1/2,HA3309/6-1,HA3309/7-1)。
文摘Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle function.The process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle function.Muscle contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular junction.Within muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate force.Regulation of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction coupling.The development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as myogenesis.Myogenic regulators coordinate the diffe rentiation of myoblasts into mature muscle fibers.Signaling pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient availability.Seve ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal muscle.Therapeutic interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular pathways.Other molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling pathway.In recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular junction.In fact,research in the last few years now suggests that these two signaling pathways are interconnected and that they jointly control physiological and pathophysiological processes in muscle fibers.In this review,we will summarize and discuss the data on these two pathways,focusing on their concerted action next to their contribution to skeletal muscle biology.However,an in-depth discussion of the noncanonical Wnt pathway,the fibro/a dipogenic precursors,or the mechanosensory aspects of these pathways is not the focus of this review.
文摘BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.
基金Science and Technology Development Foundation Program of Nanjing Medical University(No.:2015NJMU132)
文摘Objective To evaluate the mental health status of family members of patients with schizophrenia in China.Methods Wan Fang,CNKI,VIP,CBM,Springer Link,Science Direct and Pub Med databases were searched to collect the relevant studies published prior to August 2016 that were about the psychological health status of the family members of patients with schizophrenia measured with the SCL-90 scale and Software Stata 11.0 was used for their meta-analysis.Results A total of 20 studies was included in this meta-analysis.Scores of somatization affection,obsessive-compulsive symptoms,interpersonal sensitivity,depression,anxiety,hostility,phobic anxiety,and paranoia ideation of the family members were significantly higher than those of general population norms in 2006(P<0.05).Scores of somatization affection,interpersonal sensitivity,depression,anxiety,hostility,phobic anxiety,paranoia ideation,and psychoticism of the family members were significantly higher than control group(P<0.05).Moreover,the difference was not statistically significant between male and female family members in mental health status(P>0.05).Conclusion Compared with the general population,psychological distress was more reported in the family members of patients with schizophrenia.There was no statistic significantly difference between male and female members.
基金Supported by National Natural Science Foundation of China,No.81873112Natural Science Foundation of Hebei Province,No.H2020423009+2 种基金Hundred Outstanding Innovative Talents Support Program of Universities in Hebei Province,No.SLRC2019043Basic Scientific Research Project of Hebei Provincial Colleges and Universities,No.JTZ2020005Scientific and Technological Capability Improvement Project of the Hebei University of Chinese Medicine,No.KTZ2019002.
文摘BACKGROUND Metabolic reprogramming has been identified as a core hallmark of cancer.Solute carrier family 2 is a major glucose carrier family.It consists of 14 members,and we mainly study solute carrier family 2 member 1(SLC2A1)and solute carrier family 2 member 2(SLC2A2)here.SLC2A1,mainly existing in human erythrocytes,brain endothelial cells,and normal placenta,was found to be increased in hepatocellular carcinoma(HCC),while SLC2A2,the major transporter of the normal liver,was decreased in HCC.AIM To identify if SLC2A1 and SLC2A2 were associated with immune infiltration in addition to participating in the metabolic reprogramming in HCC.METHODS The expression levels of SLC2A1 and SLC2A2 were tested in HepG2 cells,HepG215 cells,and multiple databases.The clinical characteristics and survival data of SLC2A1 and SLC2A2 were examined by multiple databases.The correlation between SLC2A1 and SLC2A2 was analyzed by multiple databases.The functions and pathways in which SLC2A1,SLC2A2,and frequently altered neighbor genes were involved were discussed in String.Immune infiltration levels and immune marker genes associated with SLC2A1 and SLC2A2 were discussed from multiple databases.RESULTS The expression level of SLC2A1 was up-regulated,but the expression level of SLC2A2 was down-regulated in HepG2 cells,HepG215 cells,and liver cancer patients.The expression levels of SLC2A1 and SLC2A2 were related to tumor volume,grade,and stage in HCC.Interestingly,the expression levels of SLC2A1 and SLC2A2 were negatively correlated.Further,high SLC2A1 expression and low SLC2A2 expression were linked to poor overall survival and relapse-free survival.SLC2A1,SLC2A2,and frequently altered neighbor genes played a major role in the occurrence and development of tumors.Notably,SLC2A1 was positively correlated with tumor immune infiltration,while SLC2A2 was negatively correlated with tumor immune infiltration.Particularly,SLC2A2 methylation was positively correlated with lymphocytes.CONCLUSION SLC2A1 and SLC2A2 are independent therapeutic targets for HCC,and they are quintessential marker molecules for predicting and regulating the number and status of immune cells in HCC.
文摘Cytokines play pleiotropic roles in human health and disease by regulating both innate and adaptive immune responses.Interleukins(ILs),a large group of cytokines,can be divided into seven families,including IL-1,IL-2,IL-6,IL-8,IL-10,IL-12,and IL-17 families.Here,we review the functions of ILs in the pathogenesis and resolution of liver diseases,such as liver inflammation(e.g.,IL-35),alcoholrelated liver disease(e.g.,IL-11),non-alcoholic steatohepatitis(e.g.,IL-22),liver fibrosis(e.g.,Il-17a),and liver cancer(e.g.,IL-8).Overall,IL-1 family members are implicated in liver inflammation induced by different etiologies,such as alcohol consumption,high-fat diet,and hepatitis viruses.IL-2 family members mainly regulate T lymphocyte and NK cell proliferation and activation,and the differentiation of T cells.IL-6 family cytokines play important roles in acute phase response in liver infection,liver regeneration,and metabolic regulation,as well as lymphocyte activation.IL-8,also known as CXCL8,is activated in chronic liver diseases,which is associated with the accumulation of neutrophils and macrophages.IL-10 family members contribute key roles to liver immune tolerance and immunosuppression in liver disease.IL-12 family cytokines influence T-cell differentiation and play an essential role in autoimmune liver disease.IL-17 subfamilies contribute to infection defense,liver inflammation,and Th17 cell differentiation.ILs interact with different type I and type II cytokine receptors to regulate intracellular signaling pathways that mediate their functions.However,most clinical studies are only performed to evaluate IL-mediated therapies on alcohol and hepatitis virus infection-induced hepatitis.More pre-clinical and clinical studies are required to evaluate IL-mediated monotherapy and synergistic therapies.
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Chikungunya fever(CF)is caused by an arbovirus whose manifestations are extremely diverse,and it has evolved with significant severity in recent years.The clinical signs triggered by the Chikungunya virus are similar to those of other arboviruses.Generally,fever starts abruptly and reaches high levels,followed by severe polyarthralgia and myalgia,as well as an erythematous or petechial maculopapular rash,varying in severity and extent.Around 40%to 60%of affected individuals report persistent arthralgia,which can last from months to years.The symptoms of CF mainly represent the tissue tropism of the virus rather than the immunopathogenesis triggered by the host's immune system.The main mechanisms associated with arthralgia have been linked to an increase in T helper type 17 cells and a consequent increase in receptor activator of nuclear factor kappa-Βligand and bone resorption.This review suggests that persistent arthralgia results from the presence of viral antigens post-infection and the constant activation of signaling lymphocytic activation molecule family member 7 in synovial macrophages,leading to local infiltration of CD4+T cells,which sustains the inflammatory process in the joints through the secretion of pro-inflammatory cytokines.The term"long chikungunya"was used in this review to refer to persistent arthralgia since,due to its manifestation over long periods after the end of the viral infection,this clinical condition seems to be characterized more as a sequel than as a symptom,given that there is no active infection involved.
基金The labor costs of the graduate students is supported by the National Social Science Fund of China(No.15BRK023).
文摘Objective:Here we evaluated the impact of varying severity of traumatic brain injury on the psychological state and demands of family caregivers.Further,we determined the most significant and least significant daily needs among family caregivers.Methods:We performed a cross-sectional descriptive study in three public hospitals in Tai'an,China.Three hundred caregivers related to traumatic brain injury victims were randomly selected.Patients had varying degrees of injuries(mild to severe).The Symptom Checklist-90(SCL-90)was used to assess family caregivers'psychological statuses.The Critical Care Family Needs Inventory(CCFNI)was used to determine family caregivers'needs.Finally,the Glasgow Coma Scale(GCS)was employed to define patients'level of traumatic brain injury.Results:SCL-90 scores for each psychological dimension were significantly higher with increasing TBI severity(p<0.05).Similarly,CCFNI scores were significantly higher with increasing TBI severity(p<0.05)for information,reassurance,and accessibility.These same dimensions were found to be the most important needs for family members of TBI injury victims,while support and comfort were the least important dimensions.Conclusions:The more severe pathogenic condition of the patient,the heavier the psychological pressure is on their family member caregivers.Medical staff should therefore pay close attention to the psychological health of family caregivers of TBI patients,especially family caregivers of critical cases.Interventions should be accordingly designed and conducted to meet the needs of family caregivers.
基金Supported by the Natural Science Foundation of Liaoning Province,No.2019-BS-279.
文摘BACKGROUND Drugs targeting mitochondria can induce mitophagy and restrain proliferation in colorectal cancer(CRC)cells.Phosphoglycerate mutase family member 5(PGAM5)activates serine/threonine PTEN-induced putative kinase 1/Parkin pathway-mediated mitophagy.However,there are few studies on the clinical and prognostic significance of expression of PGAM5 protein and mitophagy-related protein Parkin in patients.AIM To assess the clinical significance of PGAM5 and Parkin proteins,as biomarkers for diagnosis and prognosis of CRC,by studying their expression in advanced CRC tissues and their association with clinicopathological parameters.METHODS The expression of PGAM5 and Parkin in CRC tissues from 100 patients was determined by immunohistochemistry.Each case was evaluated by using a combined scoring method based on signal intensity staining(scored 0-3)and the proportion of positively stained cancer cells(scored 0-4).The final staining score was calculated as the intensity score multiplied by the proportion score.Specimens were categorized as either high or low expression according to the Youden index,and the association between the expression of PGAM5 or Parkin and clinicopathological factors was ascertained.Additionally,we employed western blot to measure PGAM5 and Parkin protein expression in six matched pairs of CRC and adjacent non-tumor tissues.RESULTS Immunohistochemical and western blot findings showed that both PGAM5 and Parkin protein expression in tumor tissues was significantly higher than that in the adjacent tissues:PGAM5 and Parkin were mainly expressed in the cytoplasm of colonic epithelial cells.PGAM5 and Parkin protein levels were significantly positively correlated in advanced CRC tissues.Moreover,reduced Parkin protein expression was an independent prognostic factor for overall survival and progression-free survival in CRC patients as evinced by multivariate analysis.CONCLUSION The expression of PGAM5 protein and mitophagy-related protein Parkin has diagnostic significance for CRC and may become new biomarkers.Parkin may be a potential marker for the survival of CRC patients.
文摘BACKGROUND 17α-Hydroxylase deficiency(17-OHD)is a rare form of congenital adrenal hyperplasia,characterized by hypertension,hypokalemia,and gonadal dysplasia.However,due to the lack of a comprehensive understanding of this disease,it is prone to misdiagnosis and missed diagnosis,and there is no complete cure.CASE SUMMARY We report a female patient with 17-OHD.The patient was admitted to the Department of Neurology of our hospital due to limb weakness.During treatment,it was found that the patient’s condition was difficult to correct except for hypokalemia,and her blood pressure was difficult to control with various antihypertensive drugs.She was then transferred to our department for further treatment.On physical examination,the patient's gonadal development was found to be abnormal,and chromosome analysis demonstrated karyotype 46,XY.Considering the possibility of 17-OHD,the cytochrome P450 family 17 subfamily A member 1(CYP17A1)test was performed to confirm the diagnosis.CONCLUSION The clinical manifestations of 17-OHD are complex.Hormone determination,imaging examination,chromosome determination and CYP17A1 gene test are helpful for early diagnosis.
基金was supported by grants from the National Natural Science Foundation of China(No.81772281)the Shandong Province Taishan Scholar Project(No.ts201712067)+1 种基金the Major Research and Development Program of Shandong Province(No.2017GSF18124)the Natural Science Foundation of Shandong Province(No.ZR2020MH218).
文摘Increasing evidence indicates that aberrant expressions of some microRNAs are associated with cancer progression.However,the roles and biological mechanisms of miRNA-16-5p in human non-small cell lung cancer(NSCLC)are not to be well studied.Here,we validated that the expression of miR-16-5p was decreased significantly in NSCLC samples and cell lines.The correlation between the clinicopathological features of NSCLC and the miR-16-5p expression showed that the expression of miR-16-5p in non-small cell lung cancer was linked with the advanced TNM stage,positive lymph node metastasis,with short overall survival(OS).Also,a negative correlation between miR-16-5p and Fermitin family member 2(FERMT2)was observed,implying there may be a potential link about their regulation.The hypothesis was further confirmed by in-silico analysis and dual-luciferase reporter assay.Moreover,we demonstrated that the transfections of miR-16-5p mimics could alter some biological characteristics of NSCLC cells remarkably accomplished by the expression variance of FERMT2 in vitro and in vivo assays.Summarily,this study demonstrated that miR-16-5p,as a tumor suppression factor in NSCLC by targeting FERMT2,could serve as one promising biomarker in the prediction for NSCLC patients.
