A herbal prescription in traditional Chinese medicine(TCM)has great complexity,with multiple components and multiple targets,making it extremely challenging to determine its bioactive compounds.Yinchenhao Tang(YCHT)ha...A herbal prescription in traditional Chinese medicine(TCM)has great complexity,with multiple components and multiple targets,making it extremely challenging to determine its bioactive compounds.Yinchenhao Tang(YCHT)has been extensively used for the treatment of jaundice disease.Although many studies have examined the efficacy and active ingredients of YCHT,there is still a lack of an in-depth systematic analysis of its effective components,mechanisms,and potential targets—especially one based on clinical patients.This study established an innovative strategy for discovering the potential targets and active compounds of YCHT based on an integrated clinical and animal experiment platform.The serum metabolic profiles and constituents of YCHT in vivo were determined by ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry(UPLC-Q-ToF-MS)-based metabolomics combined with a serum pharmacochemistry method.Moreover,a compound–target–pathway network was constructed and analyzed by network pharmacology and ingenuity pathway analysis(IPA).We found that eight active components could modulate five key targets.These key targets were further verified by enzyme-linked immunosorbent assay(ELISA),which indicated that YCHT exerts therapeutic effects by targeting cholesterol 7a-hydroxylase(CYP7A1),multidrug-resistance-associated protein 2(ABCC2),multidrug-resistance-associated protein 3(ABCC3),uridine diphosphate glucuronosyl transferase 1A1(UGT1A1),and farnesoid X receptor(FXR),and by regulating metabolic pathways including primary bile acid biosynthesis,porphyrin and chlorophyll metabolism,and biliary secretion.Eight main effective compounds were discovered and correlated with the key targets and pathways.In this way,we demonstrate that this integrated strategy can be successfully applied for the effective discovery of the active compounds and therapeutic targets of an herbal prescription.展开更多
[Objective] To develop a new antiviral agent with high and long efficacy, wide spectrum, low toxicity and low cost from traditional Chinese herbal medicine and their compound. [Method] The "Quxie" (i.e. elim...[Objective] To develop a new antiviral agent with high and long efficacy, wide spectrum, low toxicity and low cost from traditional Chinese herbal medicine and their compound. [Method] The "Quxie" (i.e. eliminating pathogenic factors) drugs including Hedyotis diffusa and Lonicera japonica and "Fuzheng" (i.e. strengthening body resistance) drugs including Radix astragali and Glycyrrhiza uralensis were taken to form an antiviral herbal compound preparation. Taking the astragalus polysaccharide monomer as control, the experiment was constructed by using the agent to treat some naturally occurring viral diseases, including Newcastle disease (ND), infectious bursal disease (IBD), duck viral hepatitis (DVH), avian influenza (AI) H9 subtype and avian swollen head syndrome. [Result] The effective rates of the agent for treatment of the above-mentioned diseases were 87%, 87%, 69%, 100% and 100%, respectively, which were higher than that of astragalus polysaccharide monomer. The cure rates for these diseases were 33%, 37%, 13%, 69% and 75%, respectively, which were significantly higher than that of astragalus polysaccharide monomer (P < 0.01). The rates of poor therapeutic efficacy were 15%, 21%, 24%, 6% and 7%, respectively, which were significantly lower than that of astragalus polysaccharide monomer (P < 0.01). [Conclusion] The Chinese herbal compound preparation shows good therapeutic effects on some avian viral diseases, which can decrease mortality rate and improve production performance of poultry more greatly than astragalus polysaccharide monomer.展开更多
Objective: To improve the efficacy of refractory midfacial peripheral T-cell non-Hodgkin’s lymphoma (MPTC-NHL) with L-asparaginase (L-ASP) based salvage chemotherapy. Methods: 21 patients with refractory MPTC-NHL wer...Objective: To improve the efficacy of refractory midfacial peripheral T-cell non-Hodgkin’s lymphoma (MPTC-NHL) with L-asparaginase (L-ASP) based salvage chemotherapy. Methods: 21 patients with refractory MPTC-NHL were analyzed. 11patients (L-ASP group) received L-asparaginase based salvage chemotherapy consisting of L-asparaginase, vincristine and dexame-thosone. 10 patients (control group) received salvage combination chemotherapy without L-asparaginase. Results: Complete remission rates were 45.6% for L-ASP group and 0.0% for control group (p<0.05). Overall response rates (CR+PR) were 63.6% for L-ASP group and 10.0% for control group, respectively (p<0.05). 2-year survival rates were 45.5% for L-ASP group and 0.0% for control group (p<0.05). The major adverse effects of L-ASP were leukopenia, elevation of serum bilirubin and hyperglycemia. Conclusion: The preliminary clinical study shows that the L-ASP based salvage chemotherapy may improve the response rate and 2-year survival rate of the patients with refractory MPTC-NHL. It is necessary to continue the study further.展开更多
Purpose: Investigation of safety and tolerability as well as therapeutic efficacy of the LeY specific humanized mAb MB311 in cancer pts with malignant effusions in a Phase II clinical trial. Experimental Design: An op...Purpose: Investigation of safety and tolerability as well as therapeutic efficacy of the LeY specific humanized mAb MB311 in cancer pts with malignant effusions in a Phase II clinical trial. Experimental Design: An openlabel, single treatment arm, uncontrolled study with MB311 (100 mg per dose, intravenous infusion on day 1 and 7) in pts with malignant effusion (ascites or pleural effusion) was conducted with the primary objective to examine safety and tolerability as well as pharmacokinetics. Secondary objectives were assessment of pharmacodynamics, volumetric measurement of the malignant effusion and obtaining data for several immunological parameters. Results: Five pts (2 pts with gastric cancer and malignant ascites, 3 pts with breast cancer and malignant pleural effusion/ascites) have completed the study. MB311 was well tolerated with only two pts showing the easily manageable side effects nausea, vomiting (up to grade 2) and one episode of skin rash (grade 2) after the first application. Data of 4 pts were available for evaluating immunologic results and efficacy. In all pts significant levels of MB311 could be detected in the systemic blood circulation and the effusion leading to increased infiltration of CD45 positive immune cells (4/5 pts) and resulting in a reduction of tumor cell counts as detected by immunocytochemistry of effusion samples in 3/5 pts). Most interestingly, the pt with the highest LeY positive tumor showed a significant reduction of effusion volume after treatment—this decrease was also evident for Her2/neu positive tumor cells which were dramatically reduced after MB311 treatment in this breast cancer pt. Conclusion: MB311 was well tolerated in patients with malignant effusions, permeated into malignant effusion and attracted immune cells leading to decreased tumor cell counts in the effusion. In the case of strong LeY expression of malignant cells in the effusion a pronounced decrease in LeY, EpCAM and Her2/neu positive tumor cells and a significant reduction of the effusion volume could be demonstrated.展开更多
BACKGROUND Severe acute pancreatitis(SAP),a condition with rapid onset,critical condition and unsatisfactory prognosis,poses a certain threat to human health,warranting optimization of relevant treatment plans to impr...BACKGROUND Severe acute pancreatitis(SAP),a condition with rapid onset,critical condition and unsatisfactory prognosis,poses a certain threat to human health,warranting optimization of relevant treatment plans to improve treatment efficacy.AIM To evaluate the efficacy and safety of computerized tomography-guided the-rapeutic percutaneous puncture catheter drainage(CT-TPPCD)combined with somatostatin(SS)in the treatment of SAP.METHODS Forty-two SAP patients admitted to The Second Affiliated Hospital of Fujian Medical University from June 2020 to June 2023 were selected.On the basis of routine treatment,20 patients received SS therapy(control group)and 22 patients were given CT-TPPCD plus SS intervention(research group).The efficacy,safety(pancreatic fistula,intra-abdominal hemorrhage,sepsis,and organ dysfunction syndrome),abdominal bloating and pain relief time,bowel recovery time,hospital stay,inflammatory indicators(C-reactive protein,interleukin-6,and pro-calcitonin),and Acute Physiology and Chronic Health Evaluation(APACHE)II score of both groups were evaluated for comparison.RESULTS Compared with the control group,the research group had a markedly higher total effective rate,faster abdominal bloating and pain relief and bowel recovery,INTRODUCTION Pancreatitis,an inflammatory disease occurring in the pancreatic tissue,is classified as either acute or chronic and is associated with high morbidity and mortality,imposing a socioeconomic burden[1,2].The pathogenesis of this disease involves early protease activation,activation of nuclear factor kappa-B-related inflammatory reactions,and infiltration of immune cells[3].Severe acute pancreatitis(SAP)is a serious condition involving systemic injury and subsequent possible organ failure,accounting for 20%of all acute pancreatitis cases[4].SAP is also characterized by rapid onset,critical illness and unsatisfactory prognosis and is correlated with serious adverse events such as systemic inflammatory response syn-drome and acute lung injury,threatening the health of patients[5,6].Therefore,timely and effective therapeutic inter-ventions are of great significance for improving patient prognosis and ensuring therapeutic effects.Somatostatin(SS),a peptide hormone that can be secreted by endocrine cells and the central nervous system,is in-volved in the regulatory mechanism of glucagon and insulin synthesis in the pancreas[7].It has complex and pleiotropic effects on the gastrointestinal tract,which can inhibit the release of gastrointestinal hormones and negatively modulate the exocrine function of the stomach,pancreas and bile,while exerting a certain influence on the absorption of the di-gestive system[8,9].SS has shown certain clinical effectiveness when applied to SAP patients and can regulate the severity of SAP and immune inflammatory responses,and this regulation is related to its influence on leukocyte apoptosis and adhesion[10,11].Computerized tomography-guided therapeutic percutaneous puncture catheter drainage(CT-TPPCD)is a surgical procedure to collect lesion fluid and pus samples from necrotic lesions and perform puncture and drainage by means of CT image examination and precise positioning[12].In the research of Liu et al[13],CT-TPPCD applied to pa-tients undergoing pancreatic surgery contributes to not only good curative effects but also a low surgical risk.Baudin et al[14]also reported that CT-TPPCD has a clinical success rate of 64.6%in patients with acute infectious necrotizing pan-creatitis,with nonfatal surgery-related complications found in only two cases,suggesting that this procedure is clinically effective and safe in the treatment of the disease.In light of the limited studies on the efficacy and safety of SS plus CT-TPPCD in SAP treatment,this study performed a relevant analysis to improve clinical outcomes in SAP patients.展开更多
Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone ...Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.展开更多
Microorganisms,including bacteria,viruses,fungi,and other eukaryotes,play critical roles in human health.An altered microbiome can be associated with complex diseases.Intratumoral microbial components are found in mul...Microorganisms,including bacteria,viruses,fungi,and other eukaryotes,play critical roles in human health.An altered microbiome can be associated with complex diseases.Intratumoral microbial components are found in multiple tumor tissues and are closely correlated with cancer initiation and development and therapy efficacy.The intratumoral microbiota may contribute to promotion of the initiation and progression of cancers by DNA mutations,activating carcinogenic pathways,promoting chronic inflammation,complement system,and initiating metastasis.Moreover,the intratumoral microbiota may not only enhance antitumor immunity via mechanisms including STING signaling activation,T and NK cell activation,TLS production,and intratumoral microbiota-derived antigen presenting,but also decrease antitumor immune responses and promote cancer progression through pathways including upregulation of ROS,promoting an anti-inflammatory environment,T cell inactivation,and immunosuppression.The effect of intratumoral microbiota on antitumor immunity is dependent on microbiota composition,crosstalk between microbiota and the cancer,and status of cancers.The intratumoral microbiota may regulate cancer cell physiology and the immune response by different signaling pathways,including ROS,β-catenin,TLR,ERK,NF-κB,and STING,among others.These viewpoints may help identify the microbiota as diagnosis or prognosis evaluation of cancers,and as new therapeutic strategy and potential therapeutic targets for cancer therapy.展开更多
The weakened protective efficacy of COVID-19 vaccines and antibodies caused by SARS-CoV-2 variants presents a global health emergency,which underscores the urgent need for universal therapeutic antibody intervention f...The weakened protective efficacy of COVID-19 vaccines and antibodies caused by SARS-CoV-2 variants presents a global health emergency,which underscores the urgent need for universal therapeutic antibody intervention for clinical patients.Here,we screened three alpacas-derived nanobodies(Nbs)with neutralizing activity from twenty RBD-specific Nbs.The three Nbs were fused with the Fc domain of human IgG,namely aVHH-11-Fc,aVHH-13-Fc and aVHH-14-Fc,which could specifically bind RBD protein and competitively inhibit the binding of ACE2 receptor to RBD.They effectively neutralized SARS-CoV-2 pseudoviruses D614G,Alpha,Beta,Gamma,Delta,and Omicron sub-lineages BA.1,BA.2,BA.4,and BA.5 and authentic SARS-CoV-2 prototype,Delta,and Omicron BA.1,BA.2 strains.In mice-adapted COVID-19 severe model,intranasal administration of aVHH-11-Fc,aVHH-13-Fc and aVHH-14-Fc effectively protected mice from lethal challenges and reduced viral loads in both the upper and lower respiratory tracts.In the COVID-19 mild model,aVHH-13-Fc,which represents the optimal neutralizing activity among the above three Nbs,effectively protected hamsters from the challenge of SARS-CoV-2 prototype,Delta,Omicron BA.1 and BA.2 by significantly reducing viral replication and pathological alterations in the lungs.In structural modeling of aVHH-13 and RBD,aVHH-13 binds to the receptor-binding motif region of RBD and interacts with some highly conserved epitopes.Taken together,our study illustrated that alpaca-derived Nbs offered a therapeutic countermeasure against SARS-CoV-2,including those Delta and Omicron variants which have evolved into global pandemic strains.展开更多
Since the utilization of anthracyclines in cancer therapy, severe cardiotoxicity has become a major obstacle. The major challenge in treating cancer patients with anthracyclines is minimizing cardiotoxicity without co...Since the utilization of anthracyclines in cancer therapy, severe cardiotoxicity has become a major obstacle. The major challenge in treating cancer patients with anthracyclines is minimizing cardiotoxicity without compromising antitumor efficacy. Herein, histone deacetylase SIRT6 expression was reduced in plasma of patients treated with anthracyclines-based chemotherapy regimens. Furthermore,overexpression of SIRT6 alleviated doxorubicin-induced cytotoxicity in cardiomyocytes, and potentiated cytotoxicity of doxorubicin in multiple cancer cell lines. Moreover, SIRT6 overexpression ameliorated doxorubicin-induced cardiotoxicity and potentiated antitumor efficacy of doxorubicin in mice, suggesting that SIRT6 overexpression could be an adjunctive therapeutic strategy during doxorubicin treatment.Mechanistically, doxorubicin-impaired mitochondria led to decreased mitochondrial respiration and ATP production. And SIRT6 enhanced mitochondrial biogenesis and mitophagy by deacetylating and inhibiting Sgk1. Thus, SIRT6 overexpression coordinated metabolic remodeling from glycolysis to mitochondrial respiration during doxorubicin treatment, which was more conducive to cardiomyocyte metabolism, thus protecting cardiomyocytes but not cancer cells against doxorubicin-induced energy deficiency. In addition, ellagic acid, a natural compound that activates SIRT6, alleviated doxorubicininduced cardiotoxicity and enhanced doxorubicin-mediated tumor regression in tumor-bearing mice.These findings provide a preclinical rationale for preventing cardiotoxicity by activating SIRT6 in cancer patients undergoing chemotherapy, but also advancing the understanding of the crucial role of SIRT6 in mitochondrial homeostasis.展开更多
Background:Hypoxic-ischemic encephalopathy(HIE)is a devastating condition affecting around 8.5 in 1000 newborns globally.Therapeutic hypothermia(TH)can reduce mortality and,to a limited extent,disability after HIE.Nev...Background:Hypoxic-ischemic encephalopathy(HIE)is a devastating condition affecting around 8.5 in 1000 newborns globally.Therapeutic hypothermia(TH)can reduce mortality and,to a limited extent,disability after HIE.Nevertheless,there is a need for new and effective treatment strategies.Cell-based treatments using mononuclear cells(MNCs),which can be sourced from umbilical cord blood,are currently being investigated.Despite promising preclinical results,there is currently no strong indicator for the clinical efficacy of the approach.This analysis aimed to provide potential explanations for this discrepancy.Methods:A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.Preclinical and clinical studies were retrieved from PubMed,Web of Science,Scopus,and clinicaltrials.gov using a predefined search strategy.A total of 17 preclinical and 7 clinical studies were included.We analyzed overall MNC efficacy in preclinical trials,the methodological quality of preclinical trials,and relevant design features in preclinical versus clinical trials.Results:There was evidence for MNC therapeutic efficacy in preclinical models of HIE.The methodological quality of preclinical studies was not optimal,and statistical design quality was particularly poor.However,methodological quality was above the standard in other fields.There were significant differences in preclinical versus clinical study design including the use of TH as a baseline treatment(only in clinical studies)and much higher MNC doses being applied in preclinical studies.Conclusions:Based on the analyzed data,it is unlikely that therapeutic effect size is massively overestimated in preclinical studies.It is more plausible that the many design differences between preclinical and clinical trials are responsible for the so far lacking proof of the efficacy of MNC treatments in HIE.Additional preclinical and clinical research is required to optimize the application of MNC for experimental HIE treatment.展开更多
Axon disconnection in the central nervous system(CNS) usually causes signal transduction failure and severe functional deficits in patients with neurological disorders. Currently, there is no cure for patients with CN...Axon disconnection in the central nervous system(CNS) usually causes signal transduction failure and severe functional deficits in patients with neurological disorders. Currently, there is no cure for patients with CNS axon injury and they usually suffer from life-long neurological defects(e.g., paralysis, loss of sensory function, and autonomic dysfunction) and life-threatening complications(e.g., autonomic dysreflexia).展开更多
Introduction: Migraine is the most common primary headache, and can cause significant disability. There are two types, migraine without aura and migraine with aura. The diagnosis of migraine is essentially clinical. W...Introduction: Migraine is the most common primary headache, and can cause significant disability. There are two types, migraine without aura and migraine with aura. The diagnosis of migraine is essentially clinical. Worldwide prevalence was estimated at 11.6% in 2009. In Africa, it is estimated at 10.4%. Objective: To describe the clinical and therapeutic aspects of migraine in Brazzaville. Patients and Methods: This was a door-to-door cross-sectional study conducted from 1<sup>st</sup> May to 1<sup> st</sup> July 2018 in the city of Brazzaville. Subjects over 18 with clearly expressed consent were included. The questionnaire covered demographic characteristics, diagnostic criteria for migraine according to the IHS, treatments taken. The degree of disability was determined using the Migraine Disability Assessment Scale (MIDAS). Statistical analysis was performed using SPSS 22.0 for MAC. Results: Of the 1017 subjects interviewed in this study, 115 (39.9%) had migraine, including 73 women (63.47%) and 42 men (36.52%). In the group of migraine sufferers, the number of cases of definite migraine was 61 (53.04%) and that of probable migraine 54 (46.95%). For 81 migraine sufferers (70.43%), stress was the triggering factor. The frequency of attacks was weekly and monthly for 30 (26.1%) and 19 (16.5%) sufferers respectively. The location of the migraine was unilateral in 38% of cases and tilted in 24.3%. The intensity of the attack was described as moderate and severe in 41.7% and 57.4% of subjects respectively. Phonophobia/photophobia accompanied the migraine in 65.2% of cases. One hundred and eight subjects were treated. Of these, 106 (98.1%) were on medication. Eleven (10.37%) had received a medical prescription, and ninety-seven (89.8%) were self-medicating. Five and three subjects were under the care of a general practitioner and a neurologist respectively. Conclusion: Migraine is a frequent pathology in Brazzaville. Its preponderance among young people and women calls for the implementation of effective prevention strategies for these already vulnerable social groups. The form without aura was the most common type. Visual aura was the most common type. Headache-related symptoms were dominated by phonophotophobia, followed by nausea and vomiting. Almost all migraine sufferers were self-medicating, and very few were under the care of a doctor. First-line analgesics and NSAIDs were the mainstay of treatment.展开更多
Development of therapeutics for brain diseases has remained challenging,in particular due to the difficulty of passing the blood-brain barrier.As a result,the current arsenal of therapeutics targeting the brain is lim...Development of therapeutics for brain diseases has remained challenging,in particular due to the difficulty of passing the blood-brain barrier.As a result,the current arsenal of therapeutics targeting the brain is limited to small,lipid-soluble drugs and there is a lack of options for treating neuroblastomas,Alzheimer’s disease,and many other devastating pathologies.Despite the advances in strategies for crossing the blood-brain barrier such as the use of nanoparticles(Hersh et al.,2022;Duan et al.,2023),such delivery systems have not yet reached clinical practice.Therefore,novel platforms for the transport of therapeutics across the blood-brain barrier remain highly desired.This specifically holds for large molecules such as monoclonal antibodies and recombinant proteins,as well as nucleotide-based therapeutics and cell therapies.Research efforts in this field are increasing exponentially,with thousands of publications in the last few years.展开更多
Parkinson's disease(PD),a prevalent neurodegenerative disorder,is chara cterized by the loss of dopaminergic neurons and the aggregation ofα-synuclein protein into Lewy bodies.While the current standards of thera...Parkinson's disease(PD),a prevalent neurodegenerative disorder,is chara cterized by the loss of dopaminergic neurons and the aggregation ofα-synuclein protein into Lewy bodies.While the current standards of therapy have been successful in providing some symptom relief,they fail to address the underlying pathophysiology of PD and as a result,they have no effect on disease progression.展开更多
Background: Helicobacter pylori (Hp) infection is the most widespread bacterial infection in the world. The infection is generally acquired in childhood, but can persist into adulthood. Eradication therapy has undergo...Background: Helicobacter pylori (Hp) infection is the most widespread bacterial infection in the world. The infection is generally acquired in childhood, but can persist into adulthood. Eradication therapy has undergone several modifications. The aim of this study was to evaluate the different therapeutic strategies used in the eradication of Helicobacter pylori infection in the Centre Hospitalier Universitaire La Reference Nationale of N’Djaména. Patients and Methods: This was a prospective, descriptive analytical study spread over one year, from September 2021 to September 2022. Patients at least 15 years of age presenting with dyspeptic symptoms, seen consecutively in a hepato-gastroenterology consultation and with a positive stool test for H. pylori infection, were included in the study. Equally, 1/3 of patients were treated with dual or triple therapy. The remaining third received quadritherapy. Results: A total of 268 patients were included in the study (mean age 38.40 ± 14.66 with extremes of 16 and 80 years). Males predominated in 58% of cases. Overall therapeutic efficacy was 88.9%. According to different therapeutic strategies, efficacy was 90.75% for dual therapy with PPI (Rabeprazole) and Amoxicillin. On the other hand, efficacy was 87% and 88.88% for PPI-based triple therapy and dual antibiotic therapy, and for PPI-based quadruple therapy and triple antibiotic therapy. Conclusion: H. pylori infection is a common disease in Chad. Dual therapy with rabeprazole combined with a high dose of amoxicillin over a period of at least two weeks showed similar if not better efficacy than triple or quadruple therapy.展开更多
Background Increasing evidence supports the role of microRNAs(miRNAs)in major depressive disorder(MDD),but the pathophysiological mechanism remains elusive.Aims To explore the mechanism of microRNA-451a(miR-451a)in th...Background Increasing evidence supports the role of microRNAs(miRNAs)in major depressive disorder(MDD),but the pathophysiological mechanism remains elusive.Aims To explore the mechanism of microRNA-451a(miR-451a)in the pathology and behaviours of depression.Methods Abnormal miRNAs such as miR-451a reported previously in the serum of patients with MDD were screened and then confirmed in a mouse model of depression induced by chronic restraint stress(CRS).Eight-week-old male C57BL/6 mice had miR-451a overexpression in the medial prefrontal cortex(mPFC)via adeno-associated virus serotype 9 vectors encoding a pri-mmu-miR-451a-GFP fusion protein followed by behavioural and pathological analyses.Finally,molecular biological experiments were conducted to investigate the potential mechanism of miR-451a against depression.Results The serum levels of miRNA-451awere significantly lower in patients with MDD,with a negative correlation with the Hamilton Depression Scale scores.Additionally,a negative association between serum miR-451a and behavioural despair or anhedonia was observed in CRS mice.Notably,miR-451a expression was significantly downregulated in the mPFC of CRS-susceptible mice.Overexpressing miR-451a in the mPFC reversed the loss of dendritic spines and the depression-like phenotype of CRS mice.Mechanistically,miR-451a could inhibit CRS-induced corticotropin-releasing factor receptor 1 expression via targeting transcription factor 2,subsequently protecting dendritic spine plasticity.Conclusions Together,these results highlighted miR-451a as a candidate biomarker and therapeutic target for MDD.展开更多
Exosomes,small tiny vesicle contains a large number of intracellular particles that employ to cause various diseases and prevent several pathological events as well in the human body.It is considered a“double-edged s...Exosomes,small tiny vesicle contains a large number of intracellular particles that employ to cause various diseases and prevent several pathological events as well in the human body.It is considered a“double-edged sword”,and depending on its biological source,the action of exosomes varies under physiological conditions.Also,the isolation and characterization of the exosomes should be performed accurately and the methodology also will vary depending on the exosome source.Moreover,the uptake of exosomes from the recipients’cells is a vital and initial step for all the physiological actions.There are different mechanisms present in the exosomes’cellular uptake to deliver their cargo to acceptor cells.Once the exosomal uptake takes place,it releases the intracellular particles that leads to activate the physiological response.Even though exosomes have lavish functions,there are some challenges associated with every step of their preparation to bring potential therapeutic efficacy.So,overcoming the pitfalls would give a desired quantity of exosomes with high purity.展开更多
Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public hea...Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.展开更多
Ganoderma lucidum,one of the most well-known edible fungi,is believed to be very beneficial for longevity and vitality.A long usage history suggests that G.lucidum has various clinical therapeutic effects.And experime...Ganoderma lucidum,one of the most well-known edible fungi,is believed to be very beneficial for longevity and vitality.A long usage history suggests that G.lucidum has various clinical therapeutic effects.And experimental studies have confirmed that G.lucidum has multiple pharmacological effects,including antitumor,anti-microbial,anti-HIV protease,and antidiabetic activity and so on.With the deepening of research,more than 300 compounds have been isolated from G.lucidum.There is an increasing population of G.lucidum-based products,and its international development is expanding.Currently,G.lucidum has drawn much attention to its chemical composition,therapeutic effect,clinical value,and safety.This paper provides a comprehensive review of these aspects to enhance the global promotion of G.lucidum.展开更多
Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal ...Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.展开更多
基金This work was supported by grants from the Key Program of National Natural Science Foundation of China(81430093,81830110,and 81861168037)Heilongjiang Touyan Innovation Team Program.
文摘A herbal prescription in traditional Chinese medicine(TCM)has great complexity,with multiple components and multiple targets,making it extremely challenging to determine its bioactive compounds.Yinchenhao Tang(YCHT)has been extensively used for the treatment of jaundice disease.Although many studies have examined the efficacy and active ingredients of YCHT,there is still a lack of an in-depth systematic analysis of its effective components,mechanisms,and potential targets—especially one based on clinical patients.This study established an innovative strategy for discovering the potential targets and active compounds of YCHT based on an integrated clinical and animal experiment platform.The serum metabolic profiles and constituents of YCHT in vivo were determined by ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry(UPLC-Q-ToF-MS)-based metabolomics combined with a serum pharmacochemistry method.Moreover,a compound–target–pathway network was constructed and analyzed by network pharmacology and ingenuity pathway analysis(IPA).We found that eight active components could modulate five key targets.These key targets were further verified by enzyme-linked immunosorbent assay(ELISA),which indicated that YCHT exerts therapeutic effects by targeting cholesterol 7a-hydroxylase(CYP7A1),multidrug-resistance-associated protein 2(ABCC2),multidrug-resistance-associated protein 3(ABCC3),uridine diphosphate glucuronosyl transferase 1A1(UGT1A1),and farnesoid X receptor(FXR),and by regulating metabolic pathways including primary bile acid biosynthesis,porphyrin and chlorophyll metabolism,and biliary secretion.Eight main effective compounds were discovered and correlated with the key targets and pathways.In this way,we demonstrate that this integrated strategy can be successfully applied for the effective discovery of the active compounds and therapeutic targets of an herbal prescription.
文摘[Objective] To develop a new antiviral agent with high and long efficacy, wide spectrum, low toxicity and low cost from traditional Chinese herbal medicine and their compound. [Method] The "Quxie" (i.e. eliminating pathogenic factors) drugs including Hedyotis diffusa and Lonicera japonica and "Fuzheng" (i.e. strengthening body resistance) drugs including Radix astragali and Glycyrrhiza uralensis were taken to form an antiviral herbal compound preparation. Taking the astragalus polysaccharide monomer as control, the experiment was constructed by using the agent to treat some naturally occurring viral diseases, including Newcastle disease (ND), infectious bursal disease (IBD), duck viral hepatitis (DVH), avian influenza (AI) H9 subtype and avian swollen head syndrome. [Result] The effective rates of the agent for treatment of the above-mentioned diseases were 87%, 87%, 69%, 100% and 100%, respectively, which were higher than that of astragalus polysaccharide monomer. The cure rates for these diseases were 33%, 37%, 13%, 69% and 75%, respectively, which were significantly higher than that of astragalus polysaccharide monomer (P < 0.01). The rates of poor therapeutic efficacy were 15%, 21%, 24%, 6% and 7%, respectively, which were significantly lower than that of astragalus polysaccharide monomer (P < 0.01). [Conclusion] The Chinese herbal compound preparation shows good therapeutic effects on some avian viral diseases, which can decrease mortality rate and improve production performance of poultry more greatly than astragalus polysaccharide monomer.
文摘Objective: To improve the efficacy of refractory midfacial peripheral T-cell non-Hodgkin’s lymphoma (MPTC-NHL) with L-asparaginase (L-ASP) based salvage chemotherapy. Methods: 21 patients with refractory MPTC-NHL were analyzed. 11patients (L-ASP group) received L-asparaginase based salvage chemotherapy consisting of L-asparaginase, vincristine and dexame-thosone. 10 patients (control group) received salvage combination chemotherapy without L-asparaginase. Results: Complete remission rates were 45.6% for L-ASP group and 0.0% for control group (p<0.05). Overall response rates (CR+PR) were 63.6% for L-ASP group and 10.0% for control group, respectively (p<0.05). 2-year survival rates were 45.5% for L-ASP group and 0.0% for control group (p<0.05). The major adverse effects of L-ASP were leukopenia, elevation of serum bilirubin and hyperglycemia. Conclusion: The preliminary clinical study shows that the L-ASP based salvage chemotherapy may improve the response rate and 2-year survival rate of the patients with refractory MPTC-NHL. It is necessary to continue the study further.
文摘Purpose: Investigation of safety and tolerability as well as therapeutic efficacy of the LeY specific humanized mAb MB311 in cancer pts with malignant effusions in a Phase II clinical trial. Experimental Design: An openlabel, single treatment arm, uncontrolled study with MB311 (100 mg per dose, intravenous infusion on day 1 and 7) in pts with malignant effusion (ascites or pleural effusion) was conducted with the primary objective to examine safety and tolerability as well as pharmacokinetics. Secondary objectives were assessment of pharmacodynamics, volumetric measurement of the malignant effusion and obtaining data for several immunological parameters. Results: Five pts (2 pts with gastric cancer and malignant ascites, 3 pts with breast cancer and malignant pleural effusion/ascites) have completed the study. MB311 was well tolerated with only two pts showing the easily manageable side effects nausea, vomiting (up to grade 2) and one episode of skin rash (grade 2) after the first application. Data of 4 pts were available for evaluating immunologic results and efficacy. In all pts significant levels of MB311 could be detected in the systemic blood circulation and the effusion leading to increased infiltration of CD45 positive immune cells (4/5 pts) and resulting in a reduction of tumor cell counts as detected by immunocytochemistry of effusion samples in 3/5 pts). Most interestingly, the pt with the highest LeY positive tumor showed a significant reduction of effusion volume after treatment—this decrease was also evident for Her2/neu positive tumor cells which were dramatically reduced after MB311 treatment in this breast cancer pt. Conclusion: MB311 was well tolerated in patients with malignant effusions, permeated into malignant effusion and attracted immune cells leading to decreased tumor cell counts in the effusion. In the case of strong LeY expression of malignant cells in the effusion a pronounced decrease in LeY, EpCAM and Her2/neu positive tumor cells and a significant reduction of the effusion volume could be demonstrated.
基金Supported by 2022 Fujian Medical University Qihang Fund General Project Plan,No.2022QH1120。
文摘BACKGROUND Severe acute pancreatitis(SAP),a condition with rapid onset,critical condition and unsatisfactory prognosis,poses a certain threat to human health,warranting optimization of relevant treatment plans to improve treatment efficacy.AIM To evaluate the efficacy and safety of computerized tomography-guided the-rapeutic percutaneous puncture catheter drainage(CT-TPPCD)combined with somatostatin(SS)in the treatment of SAP.METHODS Forty-two SAP patients admitted to The Second Affiliated Hospital of Fujian Medical University from June 2020 to June 2023 were selected.On the basis of routine treatment,20 patients received SS therapy(control group)and 22 patients were given CT-TPPCD plus SS intervention(research group).The efficacy,safety(pancreatic fistula,intra-abdominal hemorrhage,sepsis,and organ dysfunction syndrome),abdominal bloating and pain relief time,bowel recovery time,hospital stay,inflammatory indicators(C-reactive protein,interleukin-6,and pro-calcitonin),and Acute Physiology and Chronic Health Evaluation(APACHE)II score of both groups were evaluated for comparison.RESULTS Compared with the control group,the research group had a markedly higher total effective rate,faster abdominal bloating and pain relief and bowel recovery,INTRODUCTION Pancreatitis,an inflammatory disease occurring in the pancreatic tissue,is classified as either acute or chronic and is associated with high morbidity and mortality,imposing a socioeconomic burden[1,2].The pathogenesis of this disease involves early protease activation,activation of nuclear factor kappa-B-related inflammatory reactions,and infiltration of immune cells[3].Severe acute pancreatitis(SAP)is a serious condition involving systemic injury and subsequent possible organ failure,accounting for 20%of all acute pancreatitis cases[4].SAP is also characterized by rapid onset,critical illness and unsatisfactory prognosis and is correlated with serious adverse events such as systemic inflammatory response syn-drome and acute lung injury,threatening the health of patients[5,6].Therefore,timely and effective therapeutic inter-ventions are of great significance for improving patient prognosis and ensuring therapeutic effects.Somatostatin(SS),a peptide hormone that can be secreted by endocrine cells and the central nervous system,is in-volved in the regulatory mechanism of glucagon and insulin synthesis in the pancreas[7].It has complex and pleiotropic effects on the gastrointestinal tract,which can inhibit the release of gastrointestinal hormones and negatively modulate the exocrine function of the stomach,pancreas and bile,while exerting a certain influence on the absorption of the di-gestive system[8,9].SS has shown certain clinical effectiveness when applied to SAP patients and can regulate the severity of SAP and immune inflammatory responses,and this regulation is related to its influence on leukocyte apoptosis and adhesion[10,11].Computerized tomography-guided therapeutic percutaneous puncture catheter drainage(CT-TPPCD)is a surgical procedure to collect lesion fluid and pus samples from necrotic lesions and perform puncture and drainage by means of CT image examination and precise positioning[12].In the research of Liu et al[13],CT-TPPCD applied to pa-tients undergoing pancreatic surgery contributes to not only good curative effects but also a low surgical risk.Baudin et al[14]also reported that CT-TPPCD has a clinical success rate of 64.6%in patients with acute infectious necrotizing pan-creatitis,with nonfatal surgery-related complications found in only two cases,suggesting that this procedure is clinically effective and safe in the treatment of the disease.In light of the limited studies on the efficacy and safety of SS plus CT-TPPCD in SAP treatment,this study performed a relevant analysis to improve clinical outcomes in SAP patients.
基金supported by the National Natural Science Foundation of China(#81872220 and#81703437)Xinjiang Uygur Autonomous Region Science and Technology Support Project(#2020E0290)+4 种基金Basic Public Welfare Research Project of Zhejiang Province(#LGF18H160034,LGC21B050011 and#LGF20H300012),Science and Technology Bureau of Jiaxing(2020AY10021)Key Research and Development and Transformation project of Qinghai Province(2021-SF-C20)Dutch Cancer Foundation(KWF project#10666)a Zhejiang Provincial Foreign Expert Program Grant,Zhejiang Provincial Key Natural Science Foundation of China(#Z20H160031)and Jiaxing Key Laboratory of Oncological Photodynamic Therapy and Targeted Drug Research,and“Innovative Jiaxing·Excellent Talent Support Program”-Top Talents in Technological Innovation.
文摘Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.
基金This work was supported by grants from the National Key Research and Development Program of China(No.2021YFE0110600)the National Natural Science Foundation of China(No.82072578,91942314,U1804281)the Outstanding Young Talents in Science and Technology Innovation of Henan Province(No.YXK2020027).
文摘Microorganisms,including bacteria,viruses,fungi,and other eukaryotes,play critical roles in human health.An altered microbiome can be associated with complex diseases.Intratumoral microbial components are found in multiple tumor tissues and are closely correlated with cancer initiation and development and therapy efficacy.The intratumoral microbiota may contribute to promotion of the initiation and progression of cancers by DNA mutations,activating carcinogenic pathways,promoting chronic inflammation,complement system,and initiating metastasis.Moreover,the intratumoral microbiota may not only enhance antitumor immunity via mechanisms including STING signaling activation,T and NK cell activation,TLS production,and intratumoral microbiota-derived antigen presenting,but also decrease antitumor immune responses and promote cancer progression through pathways including upregulation of ROS,promoting an anti-inflammatory environment,T cell inactivation,and immunosuppression.The effect of intratumoral microbiota on antitumor immunity is dependent on microbiota composition,crosstalk between microbiota and the cancer,and status of cancers.The intratumoral microbiota may regulate cancer cell physiology and the immune response by different signaling pathways,including ROS,β-catenin,TLR,ERK,NF-κB,and STING,among others.These viewpoints may help identify the microbiota as diagnosis or prognosis evaluation of cancers,and as new therapeutic strategy and potential therapeutic targets for cancer therapy.
基金This work was supported by Jilin Province Youth Talent Support Project(grant number QT202115).
文摘The weakened protective efficacy of COVID-19 vaccines and antibodies caused by SARS-CoV-2 variants presents a global health emergency,which underscores the urgent need for universal therapeutic antibody intervention for clinical patients.Here,we screened three alpacas-derived nanobodies(Nbs)with neutralizing activity from twenty RBD-specific Nbs.The three Nbs were fused with the Fc domain of human IgG,namely aVHH-11-Fc,aVHH-13-Fc and aVHH-14-Fc,which could specifically bind RBD protein and competitively inhibit the binding of ACE2 receptor to RBD.They effectively neutralized SARS-CoV-2 pseudoviruses D614G,Alpha,Beta,Gamma,Delta,and Omicron sub-lineages BA.1,BA.2,BA.4,and BA.5 and authentic SARS-CoV-2 prototype,Delta,and Omicron BA.1,BA.2 strains.In mice-adapted COVID-19 severe model,intranasal administration of aVHH-11-Fc,aVHH-13-Fc and aVHH-14-Fc effectively protected mice from lethal challenges and reduced viral loads in both the upper and lower respiratory tracts.In the COVID-19 mild model,aVHH-13-Fc,which represents the optimal neutralizing activity among the above three Nbs,effectively protected hamsters from the challenge of SARS-CoV-2 prototype,Delta,Omicron BA.1 and BA.2 by significantly reducing viral replication and pathological alterations in the lungs.In structural modeling of aVHH-13 and RBD,aVHH-13 binds to the receptor-binding motif region of RBD and interacts with some highly conserved epitopes.Taken together,our study illustrated that alpaca-derived Nbs offered a therapeutic countermeasure against SARS-CoV-2,including those Delta and Omicron variants which have evolved into global pandemic strains.
基金supported by the National Natural Science Foundation of China (81871095 and 82170873)the National Key R&D Program of China (2018YFC2000304)+1 种基金the Tsinghua Precision Medicine Foundation (10001020132, China)the Tsinghua University Spring Breeze Fund (20211080005, China)。
文摘Since the utilization of anthracyclines in cancer therapy, severe cardiotoxicity has become a major obstacle. The major challenge in treating cancer patients with anthracyclines is minimizing cardiotoxicity without compromising antitumor efficacy. Herein, histone deacetylase SIRT6 expression was reduced in plasma of patients treated with anthracyclines-based chemotherapy regimens. Furthermore,overexpression of SIRT6 alleviated doxorubicin-induced cytotoxicity in cardiomyocytes, and potentiated cytotoxicity of doxorubicin in multiple cancer cell lines. Moreover, SIRT6 overexpression ameliorated doxorubicin-induced cardiotoxicity and potentiated antitumor efficacy of doxorubicin in mice, suggesting that SIRT6 overexpression could be an adjunctive therapeutic strategy during doxorubicin treatment.Mechanistically, doxorubicin-impaired mitochondria led to decreased mitochondrial respiration and ATP production. And SIRT6 enhanced mitochondrial biogenesis and mitophagy by deacetylating and inhibiting Sgk1. Thus, SIRT6 overexpression coordinated metabolic remodeling from glycolysis to mitochondrial respiration during doxorubicin treatment, which was more conducive to cardiomyocyte metabolism, thus protecting cardiomyocytes but not cancer cells against doxorubicin-induced energy deficiency. In addition, ellagic acid, a natural compound that activates SIRT6, alleviated doxorubicininduced cardiotoxicity and enhanced doxorubicin-mediated tumor regression in tumor-bearing mice.These findings provide a preclinical rationale for preventing cardiotoxicity by activating SIRT6 in cancer patients undergoing chemotherapy, but also advancing the understanding of the crucial role of SIRT6 in mitochondrial homeostasis.
基金Academy of Medical Sciences(Newton Advanced Fellowship),Grant/Award Number:NAF\R11\1010。
文摘Background:Hypoxic-ischemic encephalopathy(HIE)is a devastating condition affecting around 8.5 in 1000 newborns globally.Therapeutic hypothermia(TH)can reduce mortality and,to a limited extent,disability after HIE.Nevertheless,there is a need for new and effective treatment strategies.Cell-based treatments using mononuclear cells(MNCs),which can be sourced from umbilical cord blood,are currently being investigated.Despite promising preclinical results,there is currently no strong indicator for the clinical efficacy of the approach.This analysis aimed to provide potential explanations for this discrepancy.Methods:A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.Preclinical and clinical studies were retrieved from PubMed,Web of Science,Scopus,and clinicaltrials.gov using a predefined search strategy.A total of 17 preclinical and 7 clinical studies were included.We analyzed overall MNC efficacy in preclinical trials,the methodological quality of preclinical trials,and relevant design features in preclinical versus clinical trials.Results:There was evidence for MNC therapeutic efficacy in preclinical models of HIE.The methodological quality of preclinical studies was not optimal,and statistical design quality was particularly poor.However,methodological quality was above the standard in other fields.There were significant differences in preclinical versus clinical study design including the use of TH as a baseline treatment(only in clinical studies)and much higher MNC doses being applied in preclinical studies.Conclusions:Based on the analyzed data,it is unlikely that therapeutic effect size is massively overestimated in preclinical studies.It is more plausible that the many design differences between preclinical and clinical trials are responsible for the so far lacking proof of the efficacy of MNC treatments in HIE.Additional preclinical and clinical research is required to optimize the application of MNC for experimental HIE treatment.
文摘Axon disconnection in the central nervous system(CNS) usually causes signal transduction failure and severe functional deficits in patients with neurological disorders. Currently, there is no cure for patients with CNS axon injury and they usually suffer from life-long neurological defects(e.g., paralysis, loss of sensory function, and autonomic dysfunction) and life-threatening complications(e.g., autonomic dysreflexia).
文摘Introduction: Migraine is the most common primary headache, and can cause significant disability. There are two types, migraine without aura and migraine with aura. The diagnosis of migraine is essentially clinical. Worldwide prevalence was estimated at 11.6% in 2009. In Africa, it is estimated at 10.4%. Objective: To describe the clinical and therapeutic aspects of migraine in Brazzaville. Patients and Methods: This was a door-to-door cross-sectional study conducted from 1<sup>st</sup> May to 1<sup> st</sup> July 2018 in the city of Brazzaville. Subjects over 18 with clearly expressed consent were included. The questionnaire covered demographic characteristics, diagnostic criteria for migraine according to the IHS, treatments taken. The degree of disability was determined using the Migraine Disability Assessment Scale (MIDAS). Statistical analysis was performed using SPSS 22.0 for MAC. Results: Of the 1017 subjects interviewed in this study, 115 (39.9%) had migraine, including 73 women (63.47%) and 42 men (36.52%). In the group of migraine sufferers, the number of cases of definite migraine was 61 (53.04%) and that of probable migraine 54 (46.95%). For 81 migraine sufferers (70.43%), stress was the triggering factor. The frequency of attacks was weekly and monthly for 30 (26.1%) and 19 (16.5%) sufferers respectively. The location of the migraine was unilateral in 38% of cases and tilted in 24.3%. The intensity of the attack was described as moderate and severe in 41.7% and 57.4% of subjects respectively. Phonophobia/photophobia accompanied the migraine in 65.2% of cases. One hundred and eight subjects were treated. Of these, 106 (98.1%) were on medication. Eleven (10.37%) had received a medical prescription, and ninety-seven (89.8%) were self-medicating. Five and three subjects were under the care of a general practitioner and a neurologist respectively. Conclusion: Migraine is a frequent pathology in Brazzaville. Its preponderance among young people and women calls for the implementation of effective prevention strategies for these already vulnerable social groups. The form without aura was the most common type. Visual aura was the most common type. Headache-related symptoms were dominated by phonophotophobia, followed by nausea and vomiting. Almost all migraine sufferers were self-medicating, and very few were under the care of a doctor. First-line analgesics and NSAIDs were the mainstay of treatment.
基金supported by Amsterdam Neuroscience(project number NDIS-2019-03,to AEW and EVB).
文摘Development of therapeutics for brain diseases has remained challenging,in particular due to the difficulty of passing the blood-brain barrier.As a result,the current arsenal of therapeutics targeting the brain is limited to small,lipid-soluble drugs and there is a lack of options for treating neuroblastomas,Alzheimer’s disease,and many other devastating pathologies.Despite the advances in strategies for crossing the blood-brain barrier such as the use of nanoparticles(Hersh et al.,2022;Duan et al.,2023),such delivery systems have not yet reached clinical practice.Therefore,novel platforms for the transport of therapeutics across the blood-brain barrier remain highly desired.This specifically holds for large molecules such as monoclonal antibodies and recombinant proteins,as well as nucleotide-based therapeutics and cell therapies.Research efforts in this field are increasing exponentially,with thousands of publications in the last few years.
基金the financial support received from the Michael J.Fox Foundation through the Target Advancement Program Grant Award (Grant No.MJFF-000649) (to HK)。
文摘Parkinson's disease(PD),a prevalent neurodegenerative disorder,is chara cterized by the loss of dopaminergic neurons and the aggregation ofα-synuclein protein into Lewy bodies.While the current standards of therapy have been successful in providing some symptom relief,they fail to address the underlying pathophysiology of PD and as a result,they have no effect on disease progression.
文摘Background: Helicobacter pylori (Hp) infection is the most widespread bacterial infection in the world. The infection is generally acquired in childhood, but can persist into adulthood. Eradication therapy has undergone several modifications. The aim of this study was to evaluate the different therapeutic strategies used in the eradication of Helicobacter pylori infection in the Centre Hospitalier Universitaire La Reference Nationale of N’Djaména. Patients and Methods: This was a prospective, descriptive analytical study spread over one year, from September 2021 to September 2022. Patients at least 15 years of age presenting with dyspeptic symptoms, seen consecutively in a hepato-gastroenterology consultation and with a positive stool test for H. pylori infection, were included in the study. Equally, 1/3 of patients were treated with dual or triple therapy. The remaining third received quadritherapy. Results: A total of 268 patients were included in the study (mean age 38.40 ± 14.66 with extremes of 16 and 80 years). Males predominated in 58% of cases. Overall therapeutic efficacy was 88.9%. According to different therapeutic strategies, efficacy was 90.75% for dual therapy with PPI (Rabeprazole) and Amoxicillin. On the other hand, efficacy was 87% and 88.88% for PPI-based triple therapy and dual antibiotic therapy, and for PPI-based quadruple therapy and triple antibiotic therapy. Conclusion: H. pylori infection is a common disease in Chad. Dual therapy with rabeprazole combined with a high dose of amoxicillin over a period of at least two weeks showed similar if not better efficacy than triple or quadruple therapy.
基金grants from the National Natural Science Foundation of China(81801378 and 81871117).
文摘Background Increasing evidence supports the role of microRNAs(miRNAs)in major depressive disorder(MDD),but the pathophysiological mechanism remains elusive.Aims To explore the mechanism of microRNA-451a(miR-451a)in the pathology and behaviours of depression.Methods Abnormal miRNAs such as miR-451a reported previously in the serum of patients with MDD were screened and then confirmed in a mouse model of depression induced by chronic restraint stress(CRS).Eight-week-old male C57BL/6 mice had miR-451a overexpression in the medial prefrontal cortex(mPFC)via adeno-associated virus serotype 9 vectors encoding a pri-mmu-miR-451a-GFP fusion protein followed by behavioural and pathological analyses.Finally,molecular biological experiments were conducted to investigate the potential mechanism of miR-451a against depression.Results The serum levels of miRNA-451awere significantly lower in patients with MDD,with a negative correlation with the Hamilton Depression Scale scores.Additionally,a negative association between serum miR-451a and behavioural despair or anhedonia was observed in CRS mice.Notably,miR-451a expression was significantly downregulated in the mPFC of CRS-susceptible mice.Overexpressing miR-451a in the mPFC reversed the loss of dendritic spines and the depression-like phenotype of CRS mice.Mechanistically,miR-451a could inhibit CRS-induced corticotropin-releasing factor receptor 1 expression via targeting transcription factor 2,subsequently protecting dendritic spine plasticity.Conclusions Together,these results highlighted miR-451a as a candidate biomarker and therapeutic target for MDD.
文摘Exosomes,small tiny vesicle contains a large number of intracellular particles that employ to cause various diseases and prevent several pathological events as well in the human body.It is considered a“double-edged sword”,and depending on its biological source,the action of exosomes varies under physiological conditions.Also,the isolation and characterization of the exosomes should be performed accurately and the methodology also will vary depending on the exosome source.Moreover,the uptake of exosomes from the recipients’cells is a vital and initial step for all the physiological actions.There are different mechanisms present in the exosomes’cellular uptake to deliver their cargo to acceptor cells.Once the exosomal uptake takes place,it releases the intracellular particles that leads to activate the physiological response.Even though exosomes have lavish functions,there are some challenges associated with every step of their preparation to bring potential therapeutic efficacy.So,overcoming the pitfalls would give a desired quantity of exosomes with high purity.
基金supported by the Natural Science Foundation of Beijing,China(7214223,7212027)the Beijing Hospitals Authority Youth Programme(QML20210601)+3 种基金the Chinese Scholarship Council(CSC)scholarship(201706210415)the National Key Research and Development Program of China(2017YFC0908800)the Beijing Municipal Health Commission(PXM2020_026272_000002,PXM2020_026272_000014)the National Natural Science Foundation of China(82070293).
文摘Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.
基金supported by Macao Science and Technology Development Fund(001/2023/ALC and 0006/2020/AKP)the Research Fund of University of Macao(CPG2023-00028-ICMS)+1 种基金the Guangxi Science and Technology Major Project(GUIKEAA22096029)Macao Young Scholars Program(AM2022022)。
文摘Ganoderma lucidum,one of the most well-known edible fungi,is believed to be very beneficial for longevity and vitality.A long usage history suggests that G.lucidum has various clinical therapeutic effects.And experimental studies have confirmed that G.lucidum has multiple pharmacological effects,including antitumor,anti-microbial,anti-HIV protease,and antidiabetic activity and so on.With the deepening of research,more than 300 compounds have been isolated from G.lucidum.There is an increasing population of G.lucidum-based products,and its international development is expanding.Currently,G.lucidum has drawn much attention to its chemical composition,therapeutic effect,clinical value,and safety.This paper provides a comprehensive review of these aspects to enhance the global promotion of G.lucidum.
基金supported by Fujian Provincial Natural Science(2020J01122587)National Natural Science Foundation of China(82103355,82102255,and 82222901)+1 种基金RGC Theme-based Research Scheme(T12-703/19-R)Research grants Council-General Research Fund(14117422 and 14117123)。
文摘Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.
