Pharmacological interventions targeting the microcirculation following traumatic spinal cord injury

Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve rse outcomes are closely related to the complex mechanism of spinal cord injury,the limited regenerative capacity of central neurons,and the inhibitory environment fo rmed by traumatic injury.Disruption to the microcirculation is an important pathophysiological mechanism of spinal cord injury.A number of therapeutic agents have been shown to improve the injury environment,mitigate secondary damage,and/or promote regeneration and repair.Among them,the spinal cord microcirculation has become an important target for the treatment of spinal cord injury.Drug inte rventions targeting the microcirculation can improve the microenvironment and promote recovery following spinal cord injury.These drugs target the structure and function of the spinal cord microcirculation and are essential for maintaining the normal function of spinal neuro ns,axons,and glial cells.This review discusses the pathophysiological role of spinal cord microcirculation in spinal cord injury,including its structure and histopathological changes.Further,it summarizes the progress of drug therapies targeting the spinal cord mic rocirc ulation after spinal cord injury.

Current pharmacological therapies for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease(NAFLD)/nonalcoholic steatohepatitis(NASH) is considered to be a hepatic manifestation of metabolic syndrome, and its incidence is rapidly increasing worldwide. It is currently the most common chronic liver disease. NASH can progress to liver cirrhosis and hepatocellular carcinoma, and may result in liver-related death. Currently, the principal treatment for NAFLD/NASH is lifestyle modification by diet and exercise. However, pharmacological therapy is indispensable because obese patients with NAFLD often have difficulty maintaining improved lifestyles. The pathogenesis of NAFLD/NASH has not been completely elucidated. However, insulin resistance, inflammatory cytokines, and oxidative stress are thought to be important in the development and/or progression of the disease. Currently, insulin sensitizers(thiazolidinediones) and antioxidants(vitamin E) seem to be the most promising therapeutic agents for NAFLD/NASH, and lipid-lowering drugs, pentoxifylline, angiotensin receptor blockers, and n-3 polyunsaturated fatty acids also have promise. However, there is a lack of consensus regarding the most effective and appropriate pharmacotherapy for NAFLD/NASH. Animal experiments suggest that herbal medicines and natural products may be promising therapeutic agents for NAFLD/NASH, but their efficacy and safety are yet to be investigated in human studies. In this paper, we review the existing and potential pharmacological therapies for NAFLD/NASH.

Current and emerging pharmacological therapy for nonalcoholic fatty liver disease

The main treatment of patients with non-alcoholic fatty liver disease(NAFLD) is life style modification including weight reduction and dietary regimen.Majority of patients are safely treated with this management and pharmacologic interventions are not recommended. However, a subgroup of NAFLD patients with non-alcoholic steatohepatitis(NASH) who cannot achieve goals of life style modification may need pharmacological therapy. One major obstacle is measurement of histological outcome by liver biopsy which is an invasive method and is not recommended routinely in these patients. Several medications, mainly targeting baseline mechanism of NAFLD, have been investigated in clinical trials for treatment of NASH with promising results. At present, only pioglitazone acting as insulin sensitizing agent and vitamin E as an antioxidant have been recommended for treatment of NASH by international guidelines. Lipid lowering agents including statins and fibrates, pentoxifylline, angiotensin receptor blockers, ursodeoxycholic acid, probiotics and synbiotics are current agents with beneficial effects for treatment of NASH but have not been approved yet. Several emerging medications are in development for treatment of NASH. Obeticholic acid, liraglutide, elafibranor, cenicriviroc and aramchol have been tested in clinical trials or are completing trials. Here in, current and upcoming medications with promising results in clinical trial for treatment of NAFLD were reviewed.

Network pharmacology:Changes the treatment mode of"one disease-one target"in cancer treatment

The article concluded that network pharmacology provides new ideas and insights into the molecular mechanism of traditional Chinese medicine(TCM)treatment of cancer.TCM is a new choice and hot spot in the field of cancer treatment.We have also previously published studies on TCM and network pharmacology.In this letter,we summarize the new paradigm of network pharmacology in cancer treatment mechanisms.

Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies

Rheumatoid arthritis（RA） is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A better understanding of how the pathological mechanisms drive the deterioration of RA progress in individuals is urgently required in order to develop therapies that will effectively treat patients at each stage of the disease progress. Here we dissect the etiology and pathology at specific stages：（i） triggering,（ii） maturation,（iii） targeting, and（iv） fulminant stage, concomitant with hyperplastic synovium, cartilage damage, bone erosion, and systemic consequences. Modern pharmacologic therapies（including conventional, biological, and novel potential small molecule disease-modifying anti-rheumatic drugs） remain the mainstay of RA treatment and there has been significant progress toward achieving disease remission without joint deformity. Despite this, a significant proportion of RA patients do not effectively respond to the current therapies and thus new drugs are urgently required. This review discusses recent advances of our understanding of RA pathogenesis, disease modifying drugs, and provides perspectives on next generation therapeutics for RA.

New trends in pharmacological treatment of acute kidney injury

Acute kidney injury,previously known as acute renal failure(AKI),is defined as an abrupt decrease in kidney function that occurs within hours or days.This new nomenclature opens a new door for possibility of treatment of developing renal injury before progression to unresolved renal failure.AKI arises due to diverse etiologic factors that rely mainly on three categories namely,prerenal,intrinsic renal,and post-renal factors with different clinical pictures,and confers a spectrum of injury ranging from mild to severe and sometimes leads to end-stage renal disease.Complexity of pathogenesis and other factors generate barriers to developing effective treatments despite a large number of experimental and clinical studies.In this review,recent advances in the potential of the currently used drugs for renoprotection,novel pharmacological targets,and prospective therapeutics for AKI are discussed.The information in this review was extracted from electronic resources(Pub Med,Google Scholar,Wiley,Science Direct,Springer),and English scientific books by using keywords including kidney,injury,recent therapy,and pharmacological targets.The articles were carefully checked for their relevance to the current manuscript.Recent targets of cellular repair or regenerative processes involved in AKI such as autophagy,ferroptosis inhibition,and p53 antagonism seem to be effective in disease control.This may help researchers and clinicians to understand how to target the interrelated molecular and cellular mechanisms underlying the pathogenesis of AKI.

Non-pharmacological cognitive intervention for aging and dementia:Current perspectives

In recent years, cognitive difficulties associated with normal aging and dementia have been receiving increased attention from both public and scientific communities. With an increase in overall lifespan, promoting healthy cognition has become a priority and a necessity for minimizing and preventing individual and societal burdens associated with cognitive dysfunctions in the elderly. The general awareness concerning the efficacy of preventive(e.g., lifestyles) and palliative treatment strategies of cognitive impairments, related to either healthy or unhealthy trajectories in cognitive aging, is continuously rising. There are several therapeutic strategies which can be broadly classified as either pharmacological or non-pharmacological/psychosocial. In face of the modest evidence for success of pharmacological treatments, especially for dementia related impairments, psychosocial interventions are progressively considered as a complementary treatment. Despite the relative spread of psychosocial interventions in clinical settings, research in this area is rather scarce with evidence for success of these therapies remaining controversial. In this work we provide an evidence based perspective on cognitive intervention(s) for healthy aging, pre-dementia(mild cognitive impairment), and dementia populations. Current evidence and future directions for improving cognitive functions in the elderly are discussed as well.

Phytochemical composition, therapeutical and pharmacological potential of Nigella sativa: a review

Plants naturally produce chemical compounds,which are used to endorse health and fight against diseases and have been used traditionally.Nigella sativa(N.sativa)has a broad spectrum of usage in traditional folk medicines and it’s a well-known medicinal herb in ancient Ayurveda,Siddha,Chinese,Arab and Unani Tibb.N.sativa stimulates the body with its natural vitalizing process and cures the disease.Phytochemically,N.sativa seed contains a wide range of fixed oils,proteins,alkaloids,saponin and essential oils.Most of the medicinal properties of N.sativa are due to the presence of the quinone constituent.Among the constituents of N.sativa,thymoquinone is one of the predominant bioactive compounds.The aim of this review is to explore the phytochemical,therapeutical and pharmacological potentials of N.sativa.N.sativa reported to have many therapeutical and pharmacological actions which includes antioxidant,antimicrobial,antidiabetic,anticancer,anti-inflammatory,immunomodulator,cardioprotective,antihyperlipidemic,pulmonary protective,hepatoprotective,nephroprotective,gastroprotective,diuretics,anti-osteoporotic,dermatologic,neuroprotective effects and also has stimulative action on the reproductive system.N.sativa seeds and its derivatives have to be isolated and further investigations should be done using animal models and clinical trials to understand its novel molecular mechanism of action.So,N.sativa and the plant derived constituents can be used in the production of new drug and to treat several diseases.

Sequencing of high-efficacy disease-modifying therapies in multiple sclerosis： perspectives and approaches

Multiple sclerosis（MS） is characterized by chronic inflammation in conjunction with neurodegeneration within the central nervous system. Most individuals with MS begin with a relapsing remitting course that later transitions to secondary progressive MS. Currently available disease-modifying therapies（DMTs） for relapsing MS have been demonstrated to reduce disease activity, however most patients require a change in therapy over the course of their disease. Treatment goals include the prevention of relapses and disability accumulation and to achieve this objective requires careful planning. Sequencing of DMTs for individual patients should be designed in such a way to maximize disease control and minimize risk based on the mechanism of action, pharmacokinetic and pharmacodynamic properties of each therapy. This includes the DMT patients are being switched from to those they are being switched to. The reversibility of immune system effects should be a key consideration for DMT sequence selection. This feature varies across DMTs and should factor more prominently in decision making as newer treatments become available for the prevention of disability accumulation in patients with progressive MS. In this short review, we discuss the landscape of existing therapies with an eye to the future when planning for optimal DMT sequencing. While no cure exists for MS, efforts are being directed toward research in neuroregeneration with the hope for positive outcomes.

Network pharmacology to predicting therapy targets of traditional Chinese medicine Kang’ai injection on breast cancer

Background:To predict the effective targets of Kang’ai injection and analyze the pharmacological mechanism for the treatment of breast cancer based on the method of network pharmacology.Methods:The Traditional Chinese Medicine Systems Pharmacology database was used to predict the effective components of the Chinese patent medicine Kang’ai injection,and GeneCards database,Online Mendelian Inheritance in Man database and the Therapeutic Target Database were used to predict the therapeutic targets of breast cancer.Cytoscape 3.7.2 was used to construct active ingredient-disease-target network.String database and Cytoscape 3.7.2 software were used to draw the protein-protein interaction network and obtain the core target.Bioconductor and R language were used to analyze the effective action target for gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.Results:There were 42 effective active ingredients in the Chinese patent medicine Kang’ai injection,which acted on 105 targets,and it had 32 components that acted on 96 targets associated with breast cancer.The target regulates various biological processes such as inflammation,angiogenesis,apoptosis and cell proliferation,and regulates pathways such as PI3K-Akt signaling pathway,MAPK signaling pathway,AGE-RAGE signaling pathway in diabetic complications and thyroid hormone signaling pathway through gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Conclusion:The treatment of breast cancer with the Chinese patent medicine Kang’ai injection is a complex mechanism process with multiple targets,multiple pathways,and multiple choices,which provides a theoretical basis for the further extraction of effective components in the treatment of breast cancer.

Photo-activated microtubule targeting drugs: Advancing therapies for colorectal cancer

Over the years immunotherapy has demonstrably improved the field of cancer treatment.However,achieving long-term survival for colorectal cancer(CRC)patients remains a significant unmet need.Combination immunotherapies incor-porating targeted drugs like MEK or multi-kinase inhibitors have offered some palliative benefit.Nevertheless,substantial gaps remain in the current therapeutic armamentarium for CRC.In recent years,there has been a surge of interest in exploring novel treatment strategies,including the application of light-activated drugs in conjunction with optical devices.This approach holds promise for achie-ving localized and targeted delivery of cytotoxic agents,such as microtubule-targeting drugs,directly to cancerous cells within the colon.

Medical therapy for nephrolithiasis:State of the art

The prevalence of nephrolithiasis is increasing worldwide.Understanding and implementing medical therapies for kidney stone prevention are critical to prevent recurrences and decrease the economic burden of this condition.Dietary and pharmacologic therapies require understanding on the part of the patient and the prescribing practitioner in order to promote compliance.Insights into occupational exposures and antibiotic use may help uncover individual risk factors.Follow-up is essential to assess response to treatment and to modify treatment plans to maximize therapeutic benefit.

Combination strategies for pharmacologic treatment of nonalcoholic steatohepatitis

Non-alcoholic steatohepatitis (NASH) is defined as hepatic steatosis, inflammation,and hepatocyte injury with or without fibrosis. It has emerged as thesecond leading indication for liver transplantation with a rising death rate in thenon-transplantable population. While there are many drugs in evaluation,currently no approved therapies are on the market for this condition. Given thisimportance, the Food and Drug Administration has provided formal guidanceregarding drug development for stopping or reversing NASH or NASH associatedfibrosis. The complex pathogenesis of NASH and its bidirectional relationshipwith metabolic syndrome has highlighted multiple drugs of interest thataddress metabolic, inflammatory, and fibrotic factors. A few promising liverspecific targets include farnesoid X receptor agonists and peroxisome proliferatoractivatedreceptor agonists. Previously studied drug classes such as glucagon-likepeptide-1 analogs or sodium/glucose transport protein 2 inhibitors have alsodemonstrated ability to improve hepatic steatosis. Here we discuss currentrationale, scientific work, and preliminary data in combining multiple drugs forthe purposes of a multimodal attack on the pathogenesis of NASH. We highlightmultiple Phase 2 and Phase 3 studies that demonstrate the potential to achieve aresponse rate higher than previously assessed monotherapies for this condition.Ultimately, one of these combination strategies may rise above in its safety andefficacy to become a part of a standardized approach to NASH.

Management of autoimmune hepatitis:Focus on pharmacologic treatments beyond corticosteroids

In autoimmune hepatitis, patients who are intolerant or with toxicity experience, non-responders, relapsers or refractory are challenging. Non-standard drugs are being tried to preemptively avoid corticosteroid-related side effects. Prognosis and quality of life of life rely on treatment optimization. Recently, emergence of powerful immunosuppressive agents, mainly from liver transplantation, challenged the supremacy of the corticosteroid regime and promise greater immunosuppression than conventional medications, offer site-specific actions and satisfactory patient tolerance. Successes in experimental models of related diseases have primed these molecular interventions. We performed a literature review on alternative treatments. Azatioprine intolerance is the principal indication for mycophenolate use butit can be used as a front-line therapy. Cyclosporine A and tacrolimus have been tested for non-responders or relapsers. Rituximab may be used as salvage therapy. Anti-tumor necrosis factor-alpha agents may be used for incomplete responses or non-responders. Methotrexate is possibly an alternative for induction of remission and maintenance in refractory patients. Cyclophosphamide has been included in the induction regimen with corticosteroids. Ursodeoxycholic acid action is mainly immunomodulatory. Non-standard treatments are coming slowly to the attention, but its use should be cautious performed by experienced centers.

Pharmacology of tetrandrine and its therapeutic use in digestive diseases

INTRODUCTIONTetrandrine (Tet) is a dibenzylisoquinoline alkaloid isolatedfrom Stephania tetrandra S. Moore, a Chinese herbalmedicine. In the past decade, lots of studies demonstrated that Tet has multiple bioactivities, It is promising to use Tet as an antifibrogenetic in liver or lung fibrosis with or without portal or pulmonary hypertension, as well as an immunomodulating and anticarcinoma drug.

Network pharmacology-based analysis of heat clearing and detoxifying drug JC724 on the treatment of colorectal cancer

BACKGROUND Heat-clearing and detoxifying drugs has protective effect on colorectal cancer(CRC).Given the complicated features of Traditional Chinese medicine formulas,network pharmacology is an effective approach for studying the multiple interactions between drugs and diseases.AIM To systematically explore the anticancer mechanism of heat-clearing and detoxifying drug JC724.METHODS This study obtained the active compounds and their targets in JC724 from Traditional Chinese Medicine System Pharmacology Database.In addition,the CRC targets were obtained from Drugbank,TTD,DisGeNET and GeneCards databases.We performed transcriptome analysis of differentially expressed genes in CRC treated with JC724.Venn diagram was used to screen the JC724-CRC intersection targets as candidate targets.Core targets were selected by proteinprotein interaction network and herb ingredient-target-disease network analysis.The functional and pathway of core targets were analysed by enrichment analysis.RESULTS We found 174 active ingredients and 283 compound targets from JC724.940 CRC-related targets were reserved from the four databases and 304 CRC differentially expressed genes were obtained by transcriptome analysis.We constructed the network and found that the five core ingredients were quercetin,βBeta sitosterol,wogonin,kaempferol and baicalein.The core JC724-CRC targets were CYP1A1,HMOX1,CXCL8,NQO1 and FOSL1.JC724 acts on multiple signaling pathways associated with CRC,including the Nrf2 signaling pathway,oxidative stress,and the IL-17 signaling pathway.CONCLUSION In this study,we systematically analyzed the active ingredients,core targets and main mechanisms of JC724 in the treatment of CRC.This study could bring a new perspective to the heat-clearing and detoxifying therapy of CRC.

四位一体中医慢性病管理模式的构建与应用

目的:构建以治未病理论为指导的“预防-治疗-康复-养生”四位一体中医慢性病管理模式,为中医非药物疗法的推广提供借鉴。方法:建设中医非药物疗法特色诊疗中心,开发中医慢性病诊疗信息管理平台,制定标准化的中医非药物疗法方案,构建中医非药物疗法慢性病管理模式。采用“线上+线下”互动和“门诊+住院”联动方式实施,采取集中式辅以卫星式管理模式。结果:患者整体就医满意度为97.63%,门诊患者人数逐年增长,至2023年服务人次年均64万,建立慢性病患者健康档案178456份。结论:“预防-治疗-康复-养生”四位一体的中医慢性病管理模式可为患者提供全面且个性化医疗服务,改善患者就医体验,提升患者满意率。

针刺治疗慢性阻塞性肺疾病的机制研究进展

慢性阻塞性肺疾病(COPD)是一种以持续性呼吸困难伴咳嗽及痰液生成为主要症状的进展性的气道反应疾病。针刺作为一种非药物疗法在COPD治疗中扮演越来越重要的角色。目前针刺治疗COPD的机制研究主要集中在炎症、免疫调节、氧化应激等方面,针刺通过以上调节机制作用于气道平滑肌,减轻其痉挛从而改善气流限制,改善肺部及全身炎症性反应而发挥治疗作用,但针刺的作用机制仍有待进一步深入研究。对针刺治疗COPD的相关机制研究进行梳理归纳,以期为揭示针刺治疗COPD的相关机制提供一定依据。

黄帝内针治疗眼部顽疾经验

黄帝内针源自《黄帝内经》,在杨真海先生的努力下,始普及传播。黄帝内针的特点是简易、安全、实用、高效,操作手法相对简单,不需人为补泻,不用提插捻转,不讲得气与否,易学习、易掌握。介绍黄帝内针的中医学术思想及其治疗眼部顽疾的临床经验,认为黄帝内针可改善各类过敏性和免疫性相关疾病所致眼部损害,适合现今社会广为推广。并举验案4则。

基于压力感受器反射调控探讨针刺降压的作用机制

当心输出量、外周阻力和血量等发生变化时,颈动脉窦和主动脉弓压力感受器反射是维持动脉血压稳定的重要神经反射机制,具有快速调节动脉血压的作用。研究表明针刺具有良好的降压作用,其降压机制可能与上调压力感受器的敏感性、促进神经元传入信息增加、帮助中枢整合传入信号、兴奋迷走神经、抑制交感神经等有关。对针刺影响压力感受器反射的各环节功能而调节血压的作用机制进行阐述,以期为临床科研工作提供一定的参考。