Modulatory role of plant-derived metabolites on host-microbiota interactions:personalized therapeutics outlook

A diverse array of microbes in and on the human body constitute the microbiota.These micro-residents continuously interact with the human host through the language of metabolites to dictate the host’s physiology in health and illnesses.Any biotic and abiotic component ensuring a balanced host-microbiota interaction are potential microbiome therapeutic agents to overcome human diseases.Plant metabolites are continually being used to treat various illnesses.These metabolites target the host’s metabolic machinery and host-gut microbiota interactions to overcome human diseases.Despite the paramount therapeutic significance of the factors affecting host-microbiota interactions,a comprehensive overview of the modulatory role of plant-derived metabolites in host-microbiota interactions is lacking.The current review puts an effort into comprehending the role of medicinal plants in gut microbiota modulation to mitigate various human illnesses.It would develop a holistic understanding of hostmicrobiota interactions and the role of effectors in health and diseases.

Regeneration of the heart:f rom molecular mechanisms to clinical therapeutics

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.

Advances in Zika virus vaccines and therapeutics:A systematic review

Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.

Perspectives for delivery of therapeutics by extravasation of biodegradable microspheres in the brain

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.

Overview of the expert consensus on the digital therapeutics in addictiverelated disorders

Background Addictive disorders have gained worldwide attention.The Chinese Association of Drug Abuse Prevention and Treatment,along with the consensus panel on digital therapeutics(DTx)for addictive disorders,has published an expert consensus on DTx for addictive disorders.1 This consensus discusses and summarises the current research and application status of DTx for addictive disorders.It identifies its clinical value,application directions,research and development principles,and future prospects.As the consensus is published in Chinese,it may not be easily accessible to an international audience.To address this,we present here an overview of the expert consensus on DTx for addictive disorders in China.The recommendations from the consensus are summarised in table 1.

Basic regulatory science behind drug substance and drug product specifications of monoclonal antibodies and other protein therapeutics

In this review,we focus on providing basics and examples for each component of the protein therapeutic specifications to interested pharmacists and biopharmaceutical scientists with a goal to strengthen understanding in regulatory science and compliance.Pharmaceutical specifications comprise a list of important quality attributes for testing,references to use for test procedures,and appropriate acceptance criteria for the tests,and they are set up to ensure that when a drug product is administered to a patient,its intended therapeutic benefits and safety can be rendered appropriately.Conformance of drug substance or drug product to the specifications is achieved by testing an article according to the listed tests and analytical methods and obtaining test results that meet the acceptance criteria.Quality attributes are chosen to be tested based on their quality risk,and consideration should be given to the merit of the analytical methods which are associated with the acceptance criteria of the specifications.Acceptance criteria are set forth primarily based on efficacy and safety profiles,with an increasing attention noted for patient-centric specifications.Discussed in this work are related guidelines that support the biopharmaceutical specification setting,how to set the acceptance criteria,and examples of the quality attributes and the analytical methods from 60 articles and 23 pharmacopeial monographs.Outlooks are also explored on process analytical technologies and other orthogonal tools which are on-trend in biopharmaceutical characterization and quality control.

Living biodrugs and how tissue source influences mesenchymal stem cell therapeutics for heart failure

In this editorial we comment on the article by Safwan M et al.We especially fo-cused on the cardiac function restoration by the use of mesenchymal stem cells(MSCs)therapy for heart failure(HF),which has emerged as a new treatment approach as“Living Biodrugs”.HF remains a significant clinical challenge due to the heart’s inability to pump blood effectively,despite advancements in medical and device-based therapies.MSCs have emerged as a promising therapeutic approach,offering benefits beyond traditional treatments through their ability to modulate inflammation,reduce fibrosis,and promote endogenous tissue rege-neration.MSCs can be derived from various tissues,including bone marrow and umbilical cord.Umbilical cord-derived MSCs exhibit superior expansion ca-pabilities,making them an attractive option for HF therapy.Conversely,bone marrow-derived MSCs have been extensively studied for their potential to im-prove cardiac function but face challenges related to cell retention and delivery.Future research is focusing on optimizing MSC sources,enhancing differentiation and immune modulation,and improving delivery methods to overcome current limitations.

From Research on TCM Images to Historiography of TCM Images——Comments on History of Chinese Image Culture:Medical Image Volume

1 Introduction.Chinese medicine has a long and rich history,dating back to the classics of the Qin and Han dynasties and extending to the integration of Chinese and Western medicine in the modern era.The vast amount of literature and scholarly works in this field makes it essential to thoroughly study the history of traditional Chinese medicine(TCM)in order to understand its development path throughout the ages and boost innovation based on tradition.This is why the sages emphasized the importance of“classifying the works into different schools and tracing back to their origins”(辨章学术,考镜源流).

A Conversation with Professor Ted Kaptchuk,a Key Architect of Modern TCM in the West

The interview was conducted on November 20th,2022 by Ioannis Solos and Charles Buck.Ted Kaptchuk(泰开阳)is a Professor of Medicine and a Professor of Global Health&Social Medicine at Harvard Medical School.In 1975,he graduated from the Macao Institute of Chinese Medicine,Macao,China.After returning to the West,Ted taught Chinese medicine throughout the States,Europe,Latin America,and Australia.Ted’s book,The Web that Has No Weaver:Understanding Chinese Medicine is a groundbreaking explanation of East Asian medicine that continues to shape the discourse of the Chinese medicine profession in the West and has been translated into 13 languages.In 1990,Ted was recruited in Harvard Medical School to help research Chinese medicine.After encountering high placebo responses in multiple acupuncture clinical trials,Ted decided to switch his career to primarily studying placebo.He has published over 300 peer-reviewed articles.He has been awarded the Lifetime Achievement Award from the Society of Acupuncture Research(2015),the Lifetime Achievement Award from the Society for Interdisciplinary Placebo Studies(2021),and the William Silen Lifetime Achievement Award in Mentoring from Harvard Medical School(2022).

Application of mesenchymal stem cell therapy for premature ovarian insufficiency: Recent advances from mechanisms to therapeutics

The incidence of premature ovarian insufficiency(POI)is increasing worldwide,particularly among younger women,posing a significant challenge to fertility.In addition to menopausal symptoms,POI leads to several complications that profoundly affect female reproductive function and overall health.Unfortunately,current clinical treatment strategies for this condition are limited and often yield unsatisfactory outcomes.These approaches typically involve hormone repla-cement therapy combined with psychological support.Recently,mesenchymal stem cell(MSC)therapies for POI have garnered considerable attention in global research.MSCs can restore ovarian reproductive and endocrine functions through diverse mechanisms,including controlling differentiation,promoting angiogenesis,regulating ovarian fibrosis,inhibiting apoptosis,enhancing autocrine and paracrine effects,suppressing inflammation,modulating the immune system,and genetic regulation.This editorial offers a succinct summary of the application of MSC therapy in the context of POI,providing evidence for groundbreaking medical approaches that have potential to enhance reproductive health and overall well-being for women.

Analysis of standardization development of TCM in Sichuan

Sichuan province is home to rich traditional Chinese medicine(TCM)resources.Recent years have seen unremitting efforts of TCM standardization in the province.By analyzing the measures and existing problems,this paper provides recommendations to boost TCM development through standardization.

Classification research of TCM pulse conditions based on multi-label voice analysis

Objective:To explore the feasibility of remotely obtaining complex information on traditional Chinese medicine(TCM)pulse conditions through voice signals.Methods: We used multi-label pulse conditions as the entry point and modeled and analyzed TCM pulse diagnosis by combining voice analysis and machine learning.Audio features were extracted from voice recordings in the TCM pulse condition dataset.The obtained features were combined with information from tongue and facial diagnoses.A multi-label pulse condition voice classification DNN model was built using 10-fold cross-validation,and the modeling methods were validated using publicly available datasets.Results: The analysis showed that the proposed method achieved an accuracy of 92.59%on the public dataset.The accuracies of the three single-label pulse manifestation models in the test set were 94.27%,96.35%,and 95.39%.The absolute accuracy of the multi-label model was 92.74%.Conclusion: Voice data analysis may serve as a remote adjunct to the TCM diagnostic method for pulse condition assessment.

Beyond the gluten-free diet:Innovations in celiac disease therapeutics

Celiac disease(CD)is an autoimmune disorder exacerbated by the ingestion of gluten in genetically susceptible individuals,leading to intestinal inflammation and damage.This chronic disease affects approximately 1%of the world’s po-pulation and is a growing health challenge due to its increasing prevalence.The development of CD is a complex interaction between genetic predispositions and environmental factors,especially gluten,culminating in a dysregulated immune response.The only effective treatment at present is a strict,lifelong gluten-free diet.However,adherence to this diet is challenging and often incomplete,so research into alternative therapies has intensified.Recent advances in under-standing the molecular and immunological aspects of CD have spearheaded the development of novel pharmacologic strategies that should provide more effec-tive and manageable treatment options.This review examines the latest inno-vations in CD therapies.The focus is on drugs in advanced clinical phases and targeting specific signaling pathways critical to the disease pathogenesis.We dis-cuss both quantitative strategies such as enzymatic degradation of gluten,and qualitative approaches including immunomodulation and induction of gluten tolerance.Innovative treatments currently under investigation include transglu-taminase inhibitors,which prevent the modification of gluten peptides,and nano-particle-based therapies to recalibrate the immune response.These new therapies not only promise to improve patient outcomes but are also expected to improve quality of life by reducing the burden of dietary restrictions.The integration of these new therapies could revolutionize the treatment of CD and shift the para-digm from strict dietary restrictions to a more flexible and patient-friendly thera-peutic approach.This review provides a comprehensive overview of the future prospects of CD treatment and emphasizes the importance of continued research and multidisciplinary collab-oration to integrate these advances into standard clinical practice.

Research Status of TCM Rehabilitation in Chronic Obstructive Pulmonary Disease (COPD)

This paper mainly analyzes the application status of TCM rehabilitation in chronic obstructive pulmonary disease(COPD),hoping to provide support and help for clinical staff through this study,and promote the further development of COPD rehabilitation program.

Exploring the Future Of TCM Cooperation--2024 China-ASEAN Traditional Chinese Medicine Industry Exchange and Promotion Conference in Taiyuan

“Traditional Chinese medicine(TCM)is very popular in Cambodia because it can treat a variety of diseases,”said Nhek Soparama,ministercounselor of the Embassy of Cambodia in China,at the 2024 China-ASEAN Traditional Chinese Medicine Industry Exchange and Promotion Conference in Taiyuan,Shanxi Province,on July 26.“Over the past two years,more than 20,000 Cambodians have received TCM treatment.”

Gene signatures to therapeutics:Assessing the potential of ivermectin against t(4;14)multiple myeloma

BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.The translocation,(t)(4;14),results in high-risk MM with limited treatment alternatives.Thus,there is an urgent need for identification and validation of potential treatments for this MM subtype.Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets.AIM To elucidate the molecular basis and search for potential effective drugs of t(4;14)MM subtype by employing a comprehensive approach.METHODS The transcriptional signature of t(4;14)MM was sourced from the Gene Expression Omnibus.Two datasets,GSE16558 and GSE116294,which included 17 and 15 t(4;14)MM bone marrow samples,and five and four normal bone marrow samples,respectively.After the differentially expressed genes were identified,the Cytohubba tool was used to screen for hub genes.Then,the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Using the STRING database and Cytoscape,protein–protein interaction networks and core targets were identified.Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis,respectively.RESULTS In this study,a total of 258 differentially expressed genes with enriched functions in cancer pathways,namely cytokine receptor interactions,nuclear factor(NF)-κB signaling pathway,lipid metabolism,atherosclerosis,and Hippo signaling pathway,were identified.Ten hub genes(cd45,vcam1,ccl3,cd56,app,cd48,btk,ccr2,cybb,and cxcl12)were identified.Nine drugs,including ivermectin,deforolimus,and isoliquiritigenin,were predicted by the Connectivity Map database to have potential therapeutic effects on t(4;14)MM.In molecular docking,ivermectin showed strong binding affinity to all 10 identified targets,especially cd45 and cybb.Ivermectin inhibited t(4;14)MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro.Furthermore,ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14)MM cells.CONCLUSION Collectively,the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14)MM diagnosis and treatment,with ivermectin emerging as a potential therapeutic alternative.

Role of gut microbiota in the pathogenesis and therapeutics of minimal hepatic encephalopathy via the gut-liver-brain axis

Minimal hepatic encephalopathy(MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety;however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.

Clinical Characteristics,Diagnosis,and Therapeutics of COVID-19:A Review

The novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)that suddenly emerged at the end of December 2019 and caused coronavirus disease 2019(COVID-19)continues to afflict humanity,not only seriously affecting healthcare systems but also leading to global social and economic imbalances.As of August 2022,there were approximately 580 million confirmed cases of COVID-19 and approximately 6.4 million confirmed deaths due to this disease.The data are sufficient to highlight the seriousness of SARS-CoV-2 infection.Although most patients with COVID-19 present primarily with respiratory symptoms,an increasing number of extrapulmonary systemic symptoms and manifestations have been associated with COVID-19.Since the outbreak of COVID-19,much has been learned about the disease and its causative agent.Therefore,great effort has been aimed at developing treatments and drug interventions to treat and reduce the incidence of COVID-19.In this narrative review,we provide a brief overview of the epidemiology,mechanisms,clinical manifestations,diagnosis,and therapeutics of COVID-19.

Toward Data-Driven Digital Therapeutics Analytics:Literature Review and Research Directions

With the advent of digital therapeutics(DTx),the development of software as a medical device(SaMD)for mobile and wearable devices has gained significant attention in recent years.Existing DTx evaluations,such as randomized clinical trials,mostly focus on verifying the effectiveness of DTx products.To acquire a deeper understanding of DTx engagement and behavioral adherence,beyond efficacy,a large amount of contextual and interaction data from mobile and wearable devices during field deployment would be required for analysis.In this work,the overall flow of the data-driven DTx analytics is reviewed to help researchers and practitioners to explore DTx datasets,to investigate contextual patterns associated with DTx usage,and to establish the(causal)relationship between DTx engagement and behavioral adherence.This review of the key components of datadriven analytics provides novel research directions in the analysis of mobile sensor and interaction datasets,which helps to iteratively improve the receptivity of existing DTx.

Validity and reliability of the evaluation tool of TCM confidence in students with TCM learning experience

Objective:This study aimed to design an evaluation scale of traditional Chinese medicine(TCM)confidence and then evaluate its validity and reliability.Methods:Three parallel samples with TCM learning experience were included in this current study.Randomly selected 500 nursing students were included factor analysis and reliability and validity analyses.After 4 weeks,200 nursing students were recruited to retest the reliability.The evaluation tool of TCM confidence included 6 dimensions and 25 entries.Results:Cronbach's a coefficient of the evaluation scale was 0.95 and that of the 6 observed aspects were higher than 0.90,and splithalf reliability was 0.81.For the retest reliability,Cronbach's a coefficient of the evaluation scale was 0.93 and that of the 6 examined aspects was all over 0.80.The index of content validity Scale Content Validity Index(S-CVI)was 0.92 and Item Content Validity Index(I-CVI)was 0.83–1.00.Conclusions:Observed results may indicate that the designed tool can be used to assess the TCM confidence level of students with TCM studied experience and also can evaluate results of TCM education during studying TCM lectures.