Advances in clinical applications of bioceramics in the new regenerative medicine era

In this editorial,we comment on the hard and soft tissue applications of different ceramic-based scaffolds prepared by different mechanisms such as 3D printing,sol-gel,and electrospinning.The new concept of regenerative medicine relies on biomaterials that can trigger in situ tissue regeneration and stem cell recruitment at the defect site.A large percentage of these biomaterials is ceramic-based as they provide the essential requirements of biomaterial principles such as tailored multisize porosity,antibacterial properties,and angiogenic properties.All these previously mentioned properties put bioceramics on top of the hierarchy of biomaterials utilized to stimulate tissue regeneration in soft and hard tissue wounds.Multiple clinical applications registered the use of these materials in triggering soft tissue regeneration in healthy and diabetic patients such as bioactive glass nanofibers.The results were promising and opened new frontiers for utilizing these materials on a larger scale.The same results were mentioned when using different forms and formulas of bioceramics in hard defect regeneration.Some bioceramics were used in combination with other polymers and biological scaffolds to improve their regenerative and mechanical properties.All this progress will enable a larger scale of patients to receive such services with ease and decrease the financial burden on the government.

Data analysis guidelines for single‑cell RNA‑seq in biomedical studies and clinical applications

The application of single-cell RNA sequencing(scRNA-seq)in biomedical research has advanced our understanding of the pathogenesis of disease and provided valuable insights into new diagnostic and therapeutic strategies.With the expansion of capacity for high-throughput scRNA-seq,including clinical samples,the analysis of these huge volumes of data has become a daunting prospect for researchers entering this field.Here,we review the workflow for typical scRNA-seq data analysis,covering raw data processing and quality control,basic data analysis applicable for almost all scRNA-seq data sets,and advanced data analysis that should be tailored to specific scientific questions.While summarizing the current methods for each analysis step,we also provide an online repository of software and wrapped-up scripts to support the implementation.Recommendations and caveats are pointed out for some specific analysis tasks and approaches.We hope this resource will be helpful to researchers engaging with scRNA-seq,in particular for emerging clinical applications.

Insight into Crosstalk Between Mitophagy and Apoptosis/Necroptosis:Mechanisms and Clinical Applications in Ischemic Stroke

Ischemic stroke is a serious cerebrovascular disease with high morbidity and mortality.As a result of ischemia-reperfusion,a cascade of pathophysiological responses is triggered by the imbalance in metabolic supply and demand,resulting in cell loss.These cellular injuries follow various molecular mechanisms solely or in combination with this disorder.Mitochondria play a driving role in the pathophysiological processes of ischemic stroke.Once ischemic stroke occurs,damaged cells would respond to such stress through mitophagy.Mitophagy is known as a conservatively selective autophagy,contributing to the removal of excessive protein aggregates and damaged intracellular components,as well as aging mitochondria.Moderate mitophagy may exert neuroprotection against stroke.Several pathways associated with the mitochondrial network collectively contribute to recovering the homeostasis of the neurovascular unit.However,excessive mitophagy would also promote ischemia-reperfusion injury.Therefore,mitophagy is a double-edged sword,which suggests that maximizing the benefits of mitophagy is one of the direction of future efforts.This review emphasized the role of mitophagy in ischemic stroke,and highlighted the crosstalk between mitophagy and apoptosis/necroptosis.

PHOTODYNAMIC THERAPY—AN UPDATE ON CLINICAL APPLICATIONS

Photodynamic therapy(PDT)has received increased attention since the regulatory approvals of several photosensitizers and light applicators in numerous countries and regions around the world.In recent years,much progress has been seen in basic research as well as clinical application.PDT clinical application has now extended from treating malignant diseases to nonmalignant diseases.This review article will present recent clinical data published in English journals.The data will be organized according to their clinical specialties.The new development and future direction in clinical applications of PDT for the management of both malignant and nonmalignant diseases will be discussed.

X-ray photon counting detectors for preclinical and clinical applications

Photon counting detectors(PCDs) have attained w ide use in X-ray imaging for various preclinical and clinical applications in the past decade. This paper briefly review s the preclinical and clinical applications of PCDs based X-ray imaging systems.Starting with an introduction of X-ray single photon detection mechanism,the brief review first describes tw o major advantages of utilizing PCDs: photon energy resolving capability and electronic noise elimination. Compared to energy integrating detectors(EIDs),the aforementioned advantages make PCDs more favorable in X-ray imaging with profound benefits such as enhanced tissue contrast,decreased image noise,increased signal to noise ratio,decreased radiation dose to the small animals and patients,and more accurate material decomposition. The utilizations of PCDs in X-ray projection radiography and computed tomography(CT)including micro-CT,dedicated breast CT,K-edge CT,and clinical CT are then review ed for the imaging applications ranging from phantoms to small animals and humans. In addition,optimization methods aiming to improve the imaging performance using PCDs are briefly review ed. PCDs are not flaw less though,and their limitations are also discussed in this review. Nevertheless,PCDs may continuously contribute to the advancement of X-ray imaging techniques in future preclinical and clinical applications.

Chemical Composition, Pharmacological Effects and Clinical Applications of Cinobufacini

Chinese medicine cinobufacini is an extract from the dried skin of Bufo bufo gargarizans Cantor,with active ingredients of bufadienolides and indole alkaloids.With further research and clinical applications,it is found that cinobufacini alone or in combination with other therapeutic methods can play an anti-tumor role by controlling proliferation of tumor cells,promoting apoptosis,inhibiting formation of tumor neovascularization,reversing multidrug resistance,and regulating immune response;it also has the functions of relieving cancer pain and regulating immune function.In this paper,the chemical composition,pharmacological effects,clinical applications,and adverse reactions of cinobufacini are summarized.However,the extraction of monomer components of cinobufacini,the relationship between different mechanisms,and the causes of adverse reactions need to be further studied.Also,high-quality clinical studies should be conducted.

Emerging roles and potential clinical applications of translatable circular RNAs in cancer and other human diseases

Circular RNAs (circRNAs) are a special class of single-stranded RNA molecules with covalently closed loops widely expressed in eukaryotic organisms. CircRNAs have long been considered to play important roles in various physiological and pathological processes as non-coding RNAs. However, circRNAs have recently garnered considerable attention due to their ability to be translated into peptides/proteins via internal ribosome entry site- or N6-methyladenosine-mediated pathways or rolling translation mechanisms. Furthermore, dysregulation of translatable circRNAs and their encoded proteins has been associated with developing and progressing diseases such as cancer. This review aims to summarize the driving mechanisms of circRNA translation and the available strategies in circRNA translation research. The main focus is on the emerging biological functions of translatable circRNAs, their regulatory mechanisms, and potential clinical applications in human diseases to provide new perspectives on disease diagnosis, prognosis, and targeted therapy.

Phytochemistry,Pharmacology,and Clinical Applications of Centella Asiatica(L.)Urban

Centella asiatica,a traditional Chinese medicine belonging to the Umbelliferae family,was recorded in the Eastern Han Dynasty.Owing to its wide developmental prospects,many scholars have extensively explored C.asiatica and made significant progress in recent years.In this study,we summarize the phytochemistry,pharmacology,and clinical applications of C.asiatica(L.)Urban based on Google Scholar,PubMed,and CNKI databases.Triterpenes and their glycosides,flavonoids,terpenoids,and volatile oils occur in herbs.The pharmacological effects mainly comprise improving cognition and memory impairment in Alzheimer's disease and anti-inflammation activity.Clinical applications include the treatment of chronic kidney diseases,malignant intestinal obstruction,radiation dermatitis,precancerous lesions,chronic prostatitis,Alzheimer's disease,and other diseases.This review provides insights into the phytochemistry,pharmacology,and clinical applications of C.asiatica and summarizes the shortcomings of the research in recent years to provide a reference for future research.

Progress of Clinical Research on the Treatment of Spinal Disorders by the Tongdu Method

Spinal disorders are diseases caused by congenital, degenerative, postural errors, trauma, and external evils that result in lesions of bones, discs, ligaments, and muscles, thus compressing the nerves. Spine-related diseases include scoliosis, intervertebral disc herniation, intervertebral stenosis, spinal fracture, ankylosing spondylitis, spinal cord injury, spinal tumour, etc., which seriously affect people’s daily life. This paper summarises the relevant studies on the treatment of spinal diseases by Tongzhu therapy. The mechanism of action of Tongzhu therapy in treating spinal diseases is closely related to the control of inflammatory factors, the improvement of local microcirculation, analgesia, and the promotion of nerve repair. This paper describes the application and modern mechanism of Tongzhu therapy in the treatment of spinal diseases, which will provide a direction for future research on Tongzhu therapy.

Biological properties and clinical applications of berberine

Berberine,an isoquinoline alkaloid isolated from the Chinese herb Coptis chinens is and other Berber is plants,has a wide range of pharmacological properties.Berberine can be used to treat many diseases,such as cancer and digestive,metabolic,cardiovascular,and neurological diseases.Berberine has protective capacities in digestive diseases.It can inhibit toxins and bacteria,including Helicobac terpylo riprotect the intestinal epithelial barrier from injury,and ameliorate liver injury.Berberine also inhibits the proliferation of various types of cancer cells and impedes invasion and metastasis.Recent evidence has confirmed that berberine improves the efficacy and safety of chemoradiotherapies.In addition,berberine regulates glycometabolism and lipid metabolism,improves energy expenditure,reduces body weight,and alleviates nonalcoholic fatty liver disease.Berberine also improves cardiovascular hemodynamics,suppresses ischemic arrhythmias,attenuates the development of atherosclerosis,and reduces hypertension.Berberine shows potent neuroprotective effects,including antioxidative,antiapoptotic,and anti-ischemic.Furthermore,berberine exerts protective effects against other diseases.The mechanisms of its functions have been extensively explored,but much remains to be clarified.This article summarizes the main pharmacological actions of berberine and its mechanisms in cancer and digestive,metabolic,cardiovascular,and neurological diseases.

Ethnopharmacology, Phytochemistry, Pharmacology, Toxicology and Clinical Applications of Radix Astragali

Radix Astragali(RA),a traditional Chinese medicine from the dried root of Astragalus species,is widely distributed throughout the temperate regions of the world.The major bioactive constituents of RA are triterpene glycosides,flavonoids,saponins,and alkaloids,and these compounds mostly exert pharmacological activities on the cardiovascular,immune,respiratory,and hepatic systems.This review summarizes the recent studies on RA and provides a comprehensive summary regarding the status of resources,ethnopharmacology,phytochemistry,pharmacology,toxicology,clinical application,and patent release of RA.We hope this review can provide a guidance for further development of therapeutic agents from RA.

Recent advances of antibody drug conjugates for clinical applications

Antibody drug conjugates(ADCs)normally compose of a humanized antibody and small molecular drug via a chemical linker.After decades of preclinical and clinical studies,a series of ADCs have been widely used for treating specific tumor types in the clinic such as brentuximab vedotin(Adcetris?)for relapsed Hodgkin’s lymphoma and systemic anaplastic large cell lymphoma,gemtuzumab ozogamicin(Mylotarg?)for acute myeloid leukemia,ado-trastuzumab emtansine(Kadcyla?)for HER2-positive metastatic breast cancer,inotuzumab ozogamicin(Besponsa?)and most recently polatuzumab vedotin-piiq(Polivy?)for B cell malignancies.More than eighty ADCs have been investigated in different clinical stages from approximately six hundred clinical trials to date.This review summarizes the key elements of ADCs and highlights recent advances of ADCs,as well as important lessons learned from clinical data,and future directions.

Autophagy-mediated regulation of neutrophils and clinical applications

Autophagy,an adaptive catabolic process,plays a cytoprotective role in enabling cellular homeostasis in the innate and adaptive immune systems.Neutrophils,the most abundant immune cells in circulation,are professional killers that orchestrate a series of events during acute inflammation.The recent literature indicates that autophagy has important roles in regulating neutrophil functions,including differentiation,degranulation,metabolism and neutrophil extracellular trap formation,that dictate neutrophil fate.It is also becoming increasingly clear that autophagy regulation is critical for neutrophils to exert their immunological activity.However,evidence regarding the systematic communication between neutrophils and autophagy is insufficient.Here,we provide an updated overview of the function of autophagy as a regulator of neutrophils and discuss its clinical relevance to provide novel insight into potentially relevant treatment strategies.

Recent advances toward clinical applications of photoacoustic microscopy: a review

Photoacoustic imaging(PAI) is an emerging technology that has been dramatically developed in the last decade. PAI, a combination of optical illumination and ultrasound detection, allows us to achieve fine resolution and obtain fruitful information of endogenous and exogenous chromophores. Among PAI imaging techniques, photoacoustic computed tomography(PACT)has been extensively used in human studies due to its deep tissue penetration(several centimeters). Alternatively, photoacoustic microscopy(PAM) offers higher resolution at the expense of penetration depth, which can also be advantageous in clinics.Recently, there has been increasing attention and studies on PAM of human tissues. In this paper, we will review principles of PAM and its applications to human tissues, including the breast tissue, carotid atheroma tissue, eye, gastrointestinal tissue,ovarian tissue and tooth ex vivo as well as the oral cavity and dermatological tissue in vivo. The paper is closed with the outlook regarding the potential applications of PAM in clinics.

Clinical application of SARS-CoV-2 antibody detection and monoclonal antibody therapies against COVID-19

The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2(SARS-CoV-2)specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodies(mAbs)in the treatment of coronavirus infectious disease 2019(COVID-19).The dynamic changes of SARS-CoV-2 specific antibodies during COVID-19 were studied.Immunoglobulin M(IgM)appeared earlier and lasted for a short time,while immunoglobulin G(IgG)appeared later and lasted longer.IgM tests can be used for early diagnosis of COVID-19,and IgG tests can be used for late diagnosis of COVID-19 and identification of asymptomatic infected persons.The combination of antibody testing and nucleic acid testing,which complement each other,can improve the diagnosis rate of COVID-19.Monoclonal anti-SARS-CoV-2 specific antibodies can be used to treat hospitalized severe and critically ill patients and non-hospitalized mild to moderate COVID-19 patients.COVID-19 convalescent plasma,highly concentrated immunoglobulin,and anti-SARS-CoV-2 specific mAbs are examples of anti-SARS-CoV-2 antibody products.Due to the continuous emergence of mutated strains of the novel coronavirus,especially omicron,its immune escape ability and infectivity are enhanced,making the effects of authorized products reduced or invalid.Therefore,the optimal application of anti-SARS-CoV-2 antibody products(especially anti-SARS-CoV-2 specific mAbs)is more effective in the treatment of COVID-19 and more conducive to patient recovery.

Emerging applications of radiomics in rectal cancer:State of the art and future perspectives

Rectal cancer(RC)is the third most commonly diagnosed cancer and has a high risk of mortality,although overall survival rates have improved.Preoperative assessments and predictions,including risk stratification,responses to therapy,long-term clinical outcomes,and gene mutation status,are crucial to guide the optimization of personalized treatment strategies.Radiomics is a novel approach that enables the evaluation of the heterogeneity and biological behavior of tumors by quantitative extraction of features from medical imaging.As these extracted features cannot be captured by visual inspection,the field holds significant promise.Recent studies have proved the rapid development of radiomics and validated its diagnostic and predictive efficacy.Nonetheless,existing radiomics research on RC is highly heterogeneous due to challenges in workflow standardization and limitations of objective cohort conditions.Here,we present a summary of existing research based on computed tomography and magnetic resonance imaging.We highlight the most salient issues in the field of radiomics and analyze the most urgent problems that require resolution.Our review provides a cutting-edge view of the use of radiomics to detect and evaluate RC,and will benefit researchers dedicated to using this state-of-the-art technology in the era of precision medicine.

Translational products of adipose tissue-derived mesenchymal stem cells:Bench to bedside applications

With developments in the field of tissue engineering and regenerative medicine,the use of biological products for the treatment of various disorders has come into the limelight among researchers and clinicians.Among all the available biological tissues,research and exploration of adipose tissue have become more robust.Adipose tissue engineering aims to develop by-products and their substitutes for their regenerative and immunomodulatory potential.The use of biodegradable scaffolds along with adipose tissue products has a major role in cellular growth,proliferation,and differentiation.Adipose tissue,apart from being the powerhouse of energy storage,also functions as the largest endocrine organ,with the release of various adipokines.The progenitor cells among the heterogeneous population in the adipose tissue are of paramount importance as they determine the capacity of regeneration of these tissues.The results of adipose-derived stemcell assisted fat grafting to provide numerous growth factors and adipokines that improve vasculogenesis,fat graft integration,and survival within the recipient tissue and promote the regeneration of tissue are promising.Adipose tissue gives rise to various by-products upon processing.This article highlights the significance and the usage of various adipose tissue by-products,their individual characteristics,and their clinical applications.

Licorice:comprehensive review of its chemical composition,pharmacodynamics,and medicinal value

Licorice,a perennial herb of Leguminosa,is one of the oldest and most widely used herbal medicines worldwide.Its distinct sweet flavor and rich medicinal value make it an integral component of traditional Chinese medicine(TCM)formulations,which continue to be widely employed.The main chemical constituents of licorice include triterpenoid saponins,flavonoids,and polysaccharides.Experimental and clinical studies have demonstrated that various extracts and pure compounds derived from licorice exhibit a wide range of pharmacological properties including anti-inflammatory,antioxidant,antimicrobial,antiviral,antitumor,immune-regulatory,and neuroprotective activities.The bioactive constituents of licorice offer therapeutic benefits for cardiovascular and cerebrovascular diseases,diabetes mellitus,and liver disorders.This comprehensive review discusses the primary chemical constituents of licorice and their pharmacological activities,describes in vivo and in vitro models employed for studying licorice,and its potential targets and mechanisms of action.Furthermore,we discuss the toxicological profile,side effects,dosage recommendations,and clinical applications of licorice.This review aims to establish a foundation for further research on the safe and effective utilization of licorice while facilitating an in-depth exploration of its properties and fostering the development of novel therapeutic agents.

Practical,regulatory and clinical considerations for development of inhalation drug products

The formulation and device collectively constitute an inhalation drug product.Development of inhaled drugs must consider the compatibility between formulation and device in order to achieve the intended pharmaceutical performance and usability of the product to improve patient compliance with treatment instruction.From the points of formulation,device and patient use,this article summarizes the inhalation drugs,including pressurized metered dose inhaler(pMDI),dry powder inhaler(DPI),and nebulizer that are currently available in the US and UK markets.It also discusses the practical considerations for the development of inhalers and provides an update on the corresponding regulations of the FDA(U.S.Food and Drug Administration)and the EMA(European Medicines Agency).

Histone methylation in pancreatic cancer and its clinical implications

Pancreatic cancer(PC)is an aggressive human cancer.Appropriate methods for the diagnosis and treatment of PC have not been found at the genetic level,thus making epigenetics a promising research path in studies of PC.Histone methylation is one of the most complicated types of epigenetic modifications and has proved crucial in the development of PC.Histone methylation is a reversible process regulated by readers,writers,and erasers.Some writers and erasers can be recognized as potential biomarkers and candidate therapeutic targets in PC because of their unusual expression in PC cells compared with normal pancreatic cells.Based on the impact that writers have on the development of PC,some inhibitors of writers have been developed.However,few inhibitors of erasers have been developed and put to clinical use.Meanwhile,there is not enough research on the reader domains.Therefore,the study of erasers and readers is still a promising area.This review focuses on the regulatory mechanism of histone methylation,and the diagnosis and chemotherapy of PC based on it.The future of epigenetic modification in PC research is also discussed.