Eradication Treatment of Helicobacter pylori Infection: Evaluation of Therapeutic Strategies in N’Djamena

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.

Development and refinement of diagnostic and therapeutic strategies for managing patients with cardiogenic stroke:An arduous journey

Cardioembolic stroke,referred to as cardiogenic stroke,is a clinical syndrome in which emboli from the heart pass through the circulatory system and cause cerebral artery embolism and corresponding brain dysfunction.Compared to other subtypes of ischemic stroke,cardiogenic stroke presents with more etiologies,greater severity,worse prognosis,and a higher recurrence rate.In this minireview,we provide new insights into the etiological classification,diagnostic methods,and interventions of cardiogenic stroke.

Glutamine addiction and therapeutic strategies in pancreatic cancer

Pancreatic cancer remains one of the most lethal diseases worldwide owing to its late diagnosis,early metastasis,and poor prognosis.Because current therapeutic options are limited,there is an urgent need to investigate novel targeted treatment strategies.Pancreatic cancer faces significant metabolic challenges,principally hypoxia and nutrient deprivation,due to specific microenvironmental constraints,including an extensive desmoplastic stromal reaction.Pancreatic cancer cells have been shown to rewire their metabolism and energy production networks to support rapid survival and proliferation.Increased glucose uptake and glycolytic pathway activity during this process have been extensively described.However,growing evidence suggests that pancreatic cancer cells are glutamine addicted.As a nitrogen source,glutamine directly(or indirectly via glutamate conversion)contributes to many anabolic processes in pancreatic cancer,including amino acids,nucleobases,and hexosamine biosynthesis.It also plays an important role in redox homeostasis,and when converted toα-ketoglutarate,glutamine serves as an energy and anaplerotic carbon source,replenishing the tricarboxylic acid cycle intermediates.The present study aims to provide a comprehensive overview of glutamine metabolic reprogramming in pancreatic cancer,focusing on potential therapeutic approaches targeting glutamine metabolism in pancreatic cancer.

Mechanisms and therapeutic strategies to combat the recurrence and progression of hepatocellular carcinoma after thermal ablation

Thermal ablation(TA),including radiofrequency ablation(RFA)and microwave ablation(MWA),has become the main treatment for early-stage hepatocellular carcinoma(HCC)due to advantages such as safety and minimal invasiveness.However,HCC is prone to local recurrence,with more aggressive malignancies after TA closely related to TA-induced changes in epithelial-mesenchymal transition(EMT)and remodeling of the tumor microenvironment(TME).According to many studies,various components of the TME undergo complex changes after TA,such as the recruitment of innate and adaptive immune cells,the release of tumor-associated antigens(TAAs)and various cytokines,the formation of a hypoxic microenvironment,and tumor angiogenesis.Changes in the TME after TA can partly enhance the anti-tumor immune response;however,this response is weak to kill the tumor completely.Certain components of the TME can induce an immunosuppressive microenvironment through complex interactions,leading to tumor recurrence and progression.How the TME is remodeled after TA and the mechanism by which the TME promotes HCC recurrence and progression are unclear.Thus,in this review,we focused on these issues to highlight potentially effective strategies for reducing and preventing the recurrence and progression of HCC after TA.

Novel therapeutic strategies targeting mitochondria as a gateway in neurodegeneration

In recent years, multiple disciplines have focused on mitochondrial biology and contributed to understanding its relevance towards adult-onset neurodegenerative disorders. These are complex dynamic organelles that have a variety of functions in ensuring cellular health and homeostasis. The plethora of mitochondrial functionalities confers them an intrinsic susceptibility to internal and external stressors(such as mutation accumulation or environmental toxins), particularly so in long-lived postmitotic cells such as neurons. Thus, it is reasonable to postulate an involvement of mitochondria in aging-associated neurological disorders, notably neurodegenerative pathologies including Alzheimer’s disease and Parkinson’s disease. On the other hand, biological effects resulting from neurodegeneration can in turn affect mitochondrial health and function, promoting a feedback loop further contributing to the progression of neuronal dysfunction and cellular death. This review examines state-of-the-art knowledge, focus on current research exploring mitochondrial health as a contributing factor to neuroregeneration, and the development of therapeutic approaches aimed at restoring mitochondrial homeostasis in a pathological setting.

Exosomes rewire the cartilage microenvironment in osteoarthritis:from intercellular communication to therapeutic strategies

Osteoarthritis(OA)is a prevalent degenerative joint disease characterized by cartilage loss and accounts for a major source of pain and disability worldwide.However,effective strategies for cartilage repair are lacking,and patients with advanced OA usually need joint replacement.Better comprehending OA pathogenesis may lead to transformative therapeutics.Recently studies have reported that exosomes act as a new means of cell-to-cell communication by delivering multiple bioactive molecules to create a particular microenvironment that tunes cartilage behavior.Specifically,exosome cargos,such as noncoding RNAs(ncRNAs)and proteins,play a crucial role in OA progression by regulating the proliferation,apoptosis,autophagy,and inflammatory response of joint cells,rendering them promising candidates for OA monitoring and treatment.This review systematically summarizes the current insight regarding the biogenesis and function of exosomes and their potential as therapeutic tools targeting cell-to-cell communication in OA,suggesting new realms to improve OA management.

Early diagnosis and therapeutic strategies for hepatocellular carcinoma:From bench to bedside

Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related deaths worldwide.The prognosis of patients with HCC remains poor largely due to the late diagnosis and lack of effective treatments.Despite being widely used,alpha-fetoprotein serology and ultrasonography have limited diagnostic performance for early-stage HCC.The emergence of omics strategies has contributed to significant advances in the development of non-invasive biomarkers for the early diagnosis of HCC including proteins,metabolites,circulating tumor deoxyribonucleic acid,and circulating non-coding ribonucleic acid.Early diagnosis is beneficial to patients as it increases the proportion who can be treated with curative treatment,thus prolonging survival outcomes.Currently,multiple clinical trials involving locoregional,systemic therapies,and combinations of these modalities are changing therapeutic strategies for different stage HCC.Success in several preclinical trials that involve immunotherapeutic innovations has created the potential to complement and enforce other treatment strategies in the future.This review summarizes the most recent advances in noninvasive early molecular detection,current therapy strategies,and potential immunotherapeutic innovations of HCC.

Altered microRNA expression in animal models of Huntington’s disease and potential therapeutic strategies

A review of recent animal models of Huntington’s disease showed many microRNAs had altered expression levels in the striatum and cerebral cortex,and which were mostly downregulated.Among the altered microRNAs were miR-9/9*,miR-29b,miR-124a,miR-132,miR-128,miR-139,miR-122,miR-138,miR-23b,miR-135b,miR-181(all downregulated)and miR-448(upregulated),and similar changes had been previously found in Huntington’s disease patients.In the animal cell studies,the altered microRNAs included miR-9,miR-9*,miR-135b,miR-222(all downregulated)and miR-214(upregulated).In the animal models,overexpression of miR-155 and miR-196a caused a decrease in mutant huntingtin mRNA and protein level,lowered the mutant huntingtin aggregates in striatum and cortex,and improved performance in behavioral tests.Improved performance in behavioral tests also occurred with overexpression of miR-132 and miR-124.In the animal cell models,overexpression of miR-22 increased the viability of rat primary cortical and striatal neurons infected with mutant huntingtin and decreased huntingtin-enriched foci of≥2μm.Also,overexpression of miR-22 enhanced the survival of rat primary striatal neurons treated with 3-nitropropionic acid.Exogenous expression of miR-214,miR-146a,miR-150,and miR-125b decreased endogenous expression of huntingtin mRNA and protein in HdhQ111/HdhQ111 cells.Further studies with animal models of Huntington’s disease are warranted to validate these findings and identify specific microRNAs whose overexpression inhibits the production of mutant huntingtin protein and other harmful processes and may provide a more effective means of treating Huntington’s disease in patients and slowing its progression.

Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives

Although gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)have always been considered rare tumors,their incidence has risen over the past few decades.They represent a highly heterogeneous group of neoplasms with several prognostic factors,including disease stage,proliferative index(Ki67),and tumor differentiation.Most of these neoplasms express somatostatin receptors on the cell surface,a feature that has important implications in terms of prognosis,diagnosis,and therapy.Although International Guidelines propose algorithms aimed at guiding therapeutic strategies,GEP-NEN patients are still very different from one another,and the need for personalized treatment continues to increase.Radical surgery is always the best option when feasible;however,up to 80%of cases are metastatic upon diagnosis.Regarding medical treatments,as GEP-NENs are characterized by relatively long overall survival,multiple therapy lines are adopted during the lifetime of these patients,but the optimum sequence to be followed has never been clearly defined.Furthermore,although new molecular markers aimed at predicting the response to therapy,as well as prognostic scores,are currently being studied,their application is still far from being part of daily clinical practice.As they represent a complex disease,with therapeutic protocols that are not completely standardized,GEP-NENs require a multidisciplinary approach.This review will provide an overview of the available therapeutic options for GEP-NENs and attempts to clarify the possible approaches for the management of these patients and to discuss future perspectives in this field.

Emerging Concepts of Pathogenesis and Comprehensive Therapeutic Strategies for Spinocerebellar Ataxia Type 3

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph Disease (MJD), is an autosomal dominant neurodegenerative disorder that predominantly involves the cerebellar, pyramidal, extrapyramidal, motor neuron and oculomotor systems. SCA3 presents strong phenotypic heterogeneity and its causative mutation of SCA3 consists of an expansion of a CAG tract in exon 10 of the ATXN3 gene, situated at 14q32.1. The ATXN3 gene is ubiquitously expressed in neuronal and non-neuronal tissues, and also participates in cellular protein quality control pathways. Mutated ATXN3 alleles present about 45 to 87CAG repeats, which result in an expanded polyglutamine tract in ataxin-3. After mutation, the polyQ tract reaches the pathological threshold (about 50 glutamine residues);the protein is considered that it might gain a neurotoxic function through some unclear mechanisms. We reviewed the literature on the pathogenesis and therapeutic strategies of spinocerebellar ataxia type 3 patients. Conversion of the expanded protein is possible by enhancing protein refolding and degradation or preventing proteolytic cleavage and prevents the protein to reach the site of toxicity by altering its ability to translocate between the nucleus and cytoplasm. Proteasomal degradation and enhancing autophagic aggregate clearance are currently proposed remarkable therapy. In spite of extensive research, the molecular mechanisms of cellular toxicity resulting from mutant ataxin-3 remain no preventive treatment is currently available. These therapeutic strategies might be able to improve sign symptoms of SCA3 as well as slow the disease progression.

Amyloid beta peptides, tau protein acetylation and therapeutic strategies for treating Alzheimer’s disease: a review

Alzheimer’s disease(AD)is the most common progressive neurodegenerative disorder.It is often lethal and currently lacks a satisfactory therapy.The disease has a specific neuro-pathological profile:accumulation of proteinaceous deposits in the brain–amyloid plaques(containingβ-amyloid peptides)and neurofibrillary tangles which are accumulation of a profusion of long stringy tangles of proteins called tau.Between the two highly recognized AD hypotheses,amyloid beta(Aβ)peptide aggregation and accumulation play a significant role and are considered as an important mechanism of AD pathology.Aβis a proteolytic product of amyloid precursor protein and genetic studies supported the relevance of Aβin AD pathogenesis.A large number of small molecules were studied for their ability to inhibit Aβ-aggregation in oligomer form or after fibrillization.However,the protein-misfolding process has certain setbacks which are inevitable due to the different morphology of protein.In recent years,it has been demonstrated that tau also plays a central role in pathogenesis of this disease.Moreover,abnormal post-translational modifications of tau,in particular,increases in acetylation at specific sites likely contribute to the toxicity of tau.Although it is evident that tau with these aberrant post-translational modifications likely facilitates neurodegeneration,the precise cellular mechanisms by which tau compromises neuronal function remain unknown.In addition,much remains to be learned about new interventions that might be developed to prevent or reduce the negative impact of tau posttranslational modifications-related damage.This review article addresses the key roles of amyloid beta and tau protein in AD as well as the possible therapeutic agents that can reduce the toxic levels of both the proteins,and thus providing beneficial effect for the AD patients.

Molecular neuro-oncology and development of targeted therapeutic strategies for brain tumors

Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify oncogenic pathways that might be amenable to targetedtherapy.Activity of the phosphoinositide 3;kinase(PI3K)/Akt pathway is often upregulated in brain tumors due to excessive stimu-lation by growth factor receptors and Ras.Loss of function of the tumor suppressor gene PTEN also frequently contributesto

The therapeutic strategies for the slit ventricle syndrome after cyst-peritoneal shunting for the temporal arachnoid cyst in children:six cases report and literatures review

Objective To investigate early diagnosis evidences,optimal therapeutic strategies and the prophylactic methods of the slit ventricle syndrome (SVS) in the temporal lobe arachnoid cysts patients who received the cyst-peritoneal(CP) shunting. Methods Six cases of SVS in the temporal lobe arachnoid cysts patients

Advances in COVID-19:the virus,the pathogenesis,and evidence-based control and therapeutic strategies

Since the outbreak of the COVID-19 pandemic in early December 2019,81174 confirmed cases and 3242 deaths have been reported in China as of March 19,2020.The Chinese people and government have contributed huge efforts to combat this disease,resulting in significant improvement of the situation,with 58 new cases(34 were imported cases)and 11 new deaths reported on March 19,2020.However,as of March 19,2020,the COVID-19 pandemic continues to develop in 167 countries/territories outside of China,and 128665 confirmed cases and 5536 deaths have been reported,with 16498 new cases and 817 new deaths occurring in last 24 hours.Therefore,the world should work together to fight against this pandemic.Here,we review the recent advances in COVID-19,including the insights in the virus,the responses of the host cells,the cytokine release syndrome,and the therapeutic approaches to inhibit the virus and alleviate the cytokine storm.By sharing knowledge and deepening our understanding of the virus and the disease pathogenesis,we believe that the community can efficiently develop effective vaccines and drugs,and the mankind will eventually win this battle against this pandemic.

Therapeutic interventions target the NLRP3 inflammasome in ulcerative colitis:Comprehensive study

One of the significant health issues in the world is the prevalence of ulcerative colitis(UC).UC is a chronic disorder that mainly affects the colon,beginning with the rectum,and can progress from asymptomatic mild inflammation to extensive inflammation of the entire colon.Understanding the underlying molecular mechanisms of UC pathogenesis emphasizes the need for innovative therapeutic approaches based on identifying molecular targets.Interestingly,in response to cellular injury,the NLR family pyrin domain containing 3(NLRP3)inflammasome is a crucial part of the inflammation and immunological reaction by promoting caspase-1 activation and the release of interleukin-1β.This review discusses the mechanisms of NLRP3 inflammasome activation by various signals and its regulation and impact on UC.

Therapeutic strategies for chronic wound infection

Chronic wounds have always been a tough fight in clinical practice,which can not only make patients suffer from pain physically and mentally but also impose a heavy burden on the society.More than one factor is relevant to each step of the development of chronic wounds.Along with the in-depth research,we have realized that figuring out the pathophysiological mechanism of chronic wounds is the foundation of treatment,while wound infection is the key point concerned.The cause of infection should be identified and prevented promptly once diagnosed.This paper mainly describes the mechanism,diagnosis and therapeutic strategies of chronic wound infection,and will put an emphasis on the principle of debridement.

NLRP3/1-mediated pyroptosis:beneficial clues for the development of novel therapies for Alzheimer’s disease

The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell death.There is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3(NLRP3)inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer’s disease.In this review,we summarize the possible pathogenic mechanisms of Alzheimer’s disease,focusing on neuroinflammation.We also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer’s disease.Finally,we examine the neuroprotective activity of small-molecule inhibitors,endogenous inhibitor proteins,microRNAs,and natural bioactive molecules that target NLRP3 and NLRP1,based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer’s disease.

Gastric cancer immunotherapy:A scientometric and clinical trial review

This letter is intended to arouse your interest in a recent review of comprehensive scientometrics and clinical trials on immunotherapy for gastric cancer(GC).Our study reviews recent advances in immunotherapy in the field of GC and highlights its new prospects as a treatment for GC.Our research reveals China’s leadership in this field,as well as new therapeutic strategies such as immune checkpoint inhibitors,cellular immunotherapy,and vaccines.The combined findings highlight the potential of immunotherapy to improve survival and quality of life in patients with stomach cancer.We believe that this study will provide important guidance for the future direction of the GC treatment field.

Glycoconjugation: An approach to cancer therapeutics

Cancer constitutes the second leading cause of death globally and is considered to have been responsible for an estimated 9.6 million fatalities in 2018.Although treatments against gastrointestinal tumors have recently advanced,those interventions can only be applied to a minority of patients at the time of diagnosis.Therefore,new therapeutic options are necessary for advanced stages of the disease.Glycosylation of antitumor agents,has been found to improve pharmacokinetic parameters,reduce side effects,and expand drug half-life in comparison with the parent compounds.In addition,glycosylation of therapeutic agents has been proven to be an effective strategy for their targeting tumor tissue,thereby reducing the doses of the glycodrugs administered to patients.This review focusses on the effect of the targeting properties of glycosylated antitumor agents on gastrointestinal tumors.

The transcorneal electrical stimulation as a novel therapeutic strategy against retinal and optic neuropathy: a review of experimental and clinical trials

Transcorneal electrical stimulation(TES) is a novel therapeutic approach to activate the retina and related downstream structures. TES has multiple advantages over traditional treatments, such as being minimally invasive and readily applicable in a routine manner.Series of animal experiments have shown that TES protects the retinal neuron from traumatic or genetic induced degeneration. These laboratory evidences support its utilization in ophthalmological therapies against various retinal and optical diseases including retinitis pigmentosa(RP), traumatic optic neuropathy,anterior ischemic optic neuropathy(AION), and retinal artery occlusions(RAOs). Several pioneering explorations sought to clarify the functional mechanism underlying the neuroprotective effects of TES. It seems that the neuroprotective effects should not be attributed to a solitary pathway, on the contrary, multiple mechanisms might contribute collectively to maintain cellular homeostasis and promote cell survival in the retina. More precise evaluations via functional and morphological techniques would determine the exact mechanism underlying the remarkable neuroprotective effect of TES. Further studies to determine the optimal parameters and the long-term stability of TES are crucial to justify the clinical significance and to establish TES as a popularized therapeutic modality against retinal and optic neuropathy.