Current scenario and challenges of clinical pharmacists to implement pharmaceutical care in DRG/DIP payment hospitals in China: a qualitative interview study.

Purpose: The Diagnosis-Related Group (DRG) or Diagnosis-Intervention Packet (DIP) payment system, now introduced in China, intends to streamline healthcare billing practices. However, its implications for clinical pharmacists, pivotal stakeholders in the healthcare system, remain inadequately explored. This study sought to assess the perceptions, challenges, and roles of clinical pharmacists in China following the introduction of the DRG or DIP payment system. Methods: Qualitative interviews were conducted among a sample of clinical pharmacists. Ten semi-structured interviews were conducted, either online or face to face. Thematic analysis was employed to identify key insights and concerns related to their professional landscape under the DRG or DIP system. Results: Clinical pharmacists exhibited variable awareness levels about the DRG or DIP system. Their roles have undergone shifts, creating a balance between traditional responsibilities and new obligations dictated by the DRG or DIP system. Professional development, particularly concerning health economics and DRG-based or DIP-based patient care, was highlighted as a key need. There were calls for policy support at both healthcare and national levels and a revised, holistic performance assessment system. The demand for more resources, be it in training platforms or personnel, was a recurrent theme. Conclusion: The DRG or DIP system's introduction in China poses both opportunities and challenges for clinical pharmacists. Addressing awareness gaps, offering robust policy support, ensuring adequate resource allocation, and recognizing the evolving role of pharmacists are crucial for harmoniously integrating the DRG or DIP system into the Chinese healthcare paradigm.

LncRNA SNHG1 alleviates myocardial ischaemia-reperfusion injury by regulating the miR-137-3p/KLF4/TRPV1 axis.

AIMS: Myocardial ischaemia-reperfusion injury (MIRI) contributes to serious myocardial injury and even death. Long non-coding RNAs (lncRNAs) have been reported to play pivotal roles in the occurrence and development of MIRI. Here, the detailed molecular mechanism of lncRNA SNHG1 in MIRI was explored. METHODS AND RESULTS: A cell model of MIRI was established through hypoxia/reoxygenation (H/R) stimulation. Cell viability and pyroptosis were evaluated utilizing MTT, PI staining, and flow cytometry. Interleukin (IL)-1ß and IL-18 secretion levels were examined by ELISA. The gene and protein expression were detected by RT-qPCR and western blot, respectively. Dual luciferase reporter gene, RIP and ChIP assays were performed to analyse the molecular interactions. The results showed that lncRNA SNHG1 overexpression alleviated H/R-induced HL-1 cell pyroptosis (all P < 0.05). LncRNA SNHG1 promoted KLF4 expression by sponging miR-137-3p. miR-137-3p silencing alleviated H/R-induced pyroptosis in HL-1 cells (all P < 0.05), which was abolished by KLF4 knockdown (all P < 0.05). KLF4 activated the AKT pathway by transcriptionally activating TRPV1 in HL-1 cells (all P < 0.05). TRPV1 knockdown reversed the alleviation of SNHG1 upregulation on H/R-induced pyroptosis in HL-1 cells (all P < 0.05). CONCLUSIONS: These results showed that lncRNA SNHG1 assuaged cardiomyocyte pyroptosis during MIRI progression by regulating the KLF4/TRPV1/AKT axis through sponging miR-137-3p. Our findings may provide novel therapeutic targets for MIRI.

Effectiveness and Safety of Lianhua Qingwen Capsules for COVID-19: A Propensity-Score Matched Cohort Study.

As a traditional Chinese medicine, Lianhua Qingwen capsules have been widely used to treat Coronavirus Disease 2019 (COVID-19). This study was aimed to demonstrate the association between treatment with Lianhua Qingwen capsules and the clinical outcomes of hospitalized patients with COVID-19. This retrospective study was conducted at four hospitals in Central China. Data of hospitalized COVID-19 patients were collected between December 19, 2019 and April 26, 2020. Based on whether Lianhua Qingwen capsules were used, patients were classified into Lianhua Qingwen and non-Lianhua Qingwen (control) groups. To control for confounding factors, we used conditional logistic regression in a propensity-score matched (PSM) cohort (1 : 1 balanced), as well as logistic regression without matching as sensitivity analysis. A total of 4918 patients were included, 2760 of whom received Lianhua Qingwen capsules and 2158 of whom did not. In the PSM model, after adjusting for confounders, the in-hospital mortality was similar between the Lianhua Qingwen group and the control group (6.8% vs. 3.3%, adjusted OR, 0.66 [95% CI, 0.38-1.15], p = 0.138). The negative conversion rate of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection was higher in the Lianhua Qingwen group (88.3% vs. 96.1%, adjusted OR, 4.02 [95% CI, 2.58-6.25], p < 0.001). The incidence of acute liver injury was comparable between the two groups (14.0% vs. 11.5%, adjusted OR: 0.85 [95% CI, 0.71-1.02], p = 0.083), and the incidence of acute kidney injury was lower in the Lianhua Qingwen group (5.3% vs. 3.0%, adjusted OR: 0.71 [95% CI, 0.50-1.00], p = 0.048). Treatment with Lianhua Qingwen capsules was not significantly associated with in-hospital mortality in COVID-19 patients. In the Lianhua Qingwen group, the negative conversion rate of SARS-CoV-2 infection was higher and the incidence of acute kidney injury was lower than in the control group.

Ambroxol for the treatment of COVID-19 among hospitalized patients: A multicenter retrospective cohort study.

Ambroxol is a commonly used mucolytic agent principally used to treat respiratory diseases, which may have a role as adjunctive therapy for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, but there is lack of evidence about its effectiveness on coronavirus disease-2019 (COVID-19) patients. To study the association between ambroxol use and clinical outcomes among hospitalized patients of COVID-19 infection. We conducted a multicenter retrospective cohort study involving 3,111 patients with confirmed SARS-CoV-2 infection from three hospitals in Wuhan from 19 December 2019 to 15 April 2020, and the primary outcome was in-hospital mortality. COVID-19 patients were classified into ambroxol and non-ambroxol groups based on the administration of ambroxol during hospitalization. Two analyses including propensity score matching (PSM) to obtain a 1:1 balanced cohort and logistic regression were used to control for confounding factors. The average age of 3,111 patients was 57.55 ± 14.93 years old, 127 of them died during hospitalization, and 924 of them used ambroxol. Treatment with ambroxol did not have a significant effect on in-hospital mortality of COVID-19 patients when compared with non-ambroxol in PSM model after adjusting for confounders (8.0% vs. 3.5%, adjusted OR, 1.03 [95% CI, 0.54-1.97], p = 0.936). Adverse events such as nausea/vomiting, headache, and rash were comparable between the two groups. Our results suggest that the use of ambroxol is not significantly associated with in-hospital mortality in COVID-19 patients, which provides evidence for evaluating the effects of ambroxol on COVID-19 patient outcomes and may be helpful for physicians considering medication alternatives for COVID-19 patients.

Drug-induced liver injury associated with dacomitinib: A case report.

Dacomitinib, the second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has been used as a first-line treatment in non-small cell lung cancer (NSCLC) patients harboring EGFR mutation. In this case, we report a patient with drug-induced liver injury (DILI) associated with the use of dacomitinib. A 59-year-old man with stage IV NSCLC was prescribed with dacomitinib; 37 days after dacomitinib administration, he was admitted to our hospital because of jaundice. Laboratory examinations revealed elevated serum levels of liver enzymes and bilirubin. Following the immediate discontinuation of dacomitinib, liver enzymes decreased but bilirubin continued to rise. Total bilirubin reached the peak (18-fold) on day 26 after dacomitinib termination and normalized on day 146 after dacomitinib discontinuation. A "probable" cause of DILI by dacomitinib was determined based on the Roussel Uclaf Causality Assessment Method. The severity of DILI was assessed as acute liver failure. To our knowledge, this is the first case of DILI caused by dacomitinib monotherapy in a real-world setting. Clinicians should pay particular attention to the possibility of DILI during dacomitinib treatment.

Voriconazole-induced severe skin allergy and neurological adverse event in a liver failure patient: A case report.

WHAT IS KNOWN AND OBJECTIVE: Triazole antifungal-associated severe skin allergy has received little attention. Here we report a case of an acute-on-chronic liver failure (ACLF) patient with diffused skin allergy pervading from the chest, abdomen, back, knees to perineum, with red colour and partially desquamation as well as a neurological adverse (insomnia) event after voriconazole treatment. CASE SUMMARY: A 40-year-old man with liver failure in our hospital had received voriconazole for invasive fungal infection therapy, and while waiting for liver transplantation exhibited a severe diffuse rash and a neurological adverse event. WHAT IS NEW AND CONCLUSION: To the best of our knowledge, this is the first report of a liver failure patient who suffered a severe allergy accompanied with a neurological adverse event after voriconazole administration.

Association Between Drug Treatments and the Incidence of Liver Injury in Hospitalized Patients With COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) has led to the emergence of global health care. In this study, we aimed to explore the association between drug treatments and the incidence of drug-induced liver injury (DILI) in hospitalized patients with COVID-19. A retrospective study was conducted on 5113 COVID-19 patients in Hubei province, among which 395 incurred liver injury. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards models. The results showed that COVID-19 patients who received antibiotics (HR 1.97, 95% CI: 1.55-2.51, p < 0.001), antifungal agents (HR 3.10, 95% CI: 1.93-4.99, p < 0.001) and corticosteroids (HR 2.31, 95% CI: 1.80-2.96, p < 0.001) had a higher risk of DILI compared to non-users. Special attention was given to the use of parenteral nutrition (HR 1.82, 95% CI: 1.31-2.52, p < 0.001) and enteral nutrition (HR 2.71, 95% CI: 1.98-3.71, p < 0.001), which were the risk factors for liver injury. In conclusion, this study suggests that the development of DILI in hospitalized patients with COVID-19 needs to be closely monitored, and the above-mentioned drug treatments may contribute to the risk of DILI.

Knowledge, Attitude and Practice of Hospital Pharmacists in Central China Towards Adverse Drug Reaction Reporting: A Multicenter Cross-Sectional Study.

Background: Healthcare professionals' knowledge and attitudes towards adverse drug reactions (ADRs) and ADR reporting play a significant role in pharmacovigilance. This study aims to investigate the gap between knowledge and practice in ADR reporting among hospital pharmacists. Methods: This study is a multi-center, cross-sectional study based on a questionnaire survey. A semi-structured questionnaire was developed including knowledge, attitudes, and practices (KAP) towards ADR reporting. From October to November 2021, questionnaires were filled out on the internet by hospital pharmacists from a central province of China. The data analysis used a one-way ANOVA to analyze the differences between the pharmacist's characteristics and knowledge and attitude, respectively. The ordinal logistic regression method was used to analyze the predictors of practice. Results: A total of 1,026 valid questionnaires from 512 medical institutions were collected. It was found that 88.8% of participants have a clear understanding of the ADR definition, while 59.6% of them have misunderstandings about the reporting time of new and serious adverse reactions. Most pharmacists showed positive attitudes towards ADR reporting. Higher education background, higher professional title, attending training, and clinical pharmacist resulted in higher knowledge scores. Higher education background, shorter working years, attending training, and from non-tertiary hospital related to higher attitude scores. In terms of practice, age, hospital type, working years, training, and pharmacist type all have significant associations with practice scores. Pharmacists' knowledge score and attitude score were significant predictors of practice score with OR being 1.19 (95% CI: 1.06, 1.33) and 1.04 (95% CI: 1.005, 1.07). Conclusion: Although most hospital pharmacists showed positive attitudes towards ADR reporting, their knowledge and practice were still insufficient. Hospital pharmacists' knowledge and attitude are associated with their practice towards ADR reporting. The training had a significant impact on the pharmacist's knowledge, attitude, and practice.

Analysis on the medication rule of traditional Chinese medicine in the treatment of COVID-19 patients.

Objective: To describe patterns of utilization of traditional Chinese medicine (TCM) in the treatment of patients with coronavirus disease 2019 (COVID-19). Methods: Adult patients with COVID-19 who received TCM treatment were divided into a non-serious group (mild and moderate types) and a serious group (severe and critical types) according to their admission conditions. The medical records and prescriptions of these patients were investigated to determine their TCM utilization patterns. Results: In all, 3,872 COVID-19 patients were included. Oral Chinese traditional patent medicine (CPM) was the most commonly used type of TCM, followed by decoction. The proportion of multi-drug combinations was higher than single drug use (55.0% vs. 45.0%). Decoction combined with oral CPM was the most common combination (39.1%, 1,514/3,872). Orally administered, injected, and externally applied CPM were significantly more common in the serious group than in the non-serious, while decoction and non-drug TCM treatments were more common in the non-serious than in the serious group. Multi-drug combinations were used for the majority of patients in both groups, mainly in the form of decoctions combined with oral CPM. Among the serious patients, injected CPM was more often used in patients who died during treatment (35.0%, 36/103). The two most common medication patterns were decoction combined with oral CPM and oral CPM alone in the two finally discharged groups. Oral CPM alone or used in combination with injected CPM were seen most commonly in the death group. Significant differences were established in TCM utilization and medication patterns among patients in three groups who had different prognoses and outcomes. Conclusions: The treatment measures and medication patterns of TCM commonly used in COVID-19 patients with the range of conditions found in this study should be further explored in the future to provide a more complete reference for COVID-19 treatment.

Novel selective hexokinase 2 inhibitor Benitrobenrazide blocks cancer cells growth by targeting glycolysis.

Accelerated glucose metabolism is a common feature of cancer cells. Hexokinase 2 (HK2) as the rate-limiting enzyme catalyzes the first step of glucose metabolism. It is overexpressed in most of the human cancers and has been a promising target for cancer therapy. Here, we report a novel selective HK2 inhibitor Benitrobenrazide (BNBZ), with nanomolar inhibitory potency. In vitro, BNBZ directly binds to HK2, induces apoptosis, and inhibits proliferation of HK2-overexpressed cancer cells. BNBZ also significantly inhibits the glycolysis of SW1990 cells by targeting HK2. The knockdown or knockout of HK2 expression in SW1990 cells can reduce their sensitivity to BNBZ. Additionally, oral administration of BNBZ can effectively inhibit tumor growth in SW1990 and SW480 xenograft models. In general, BNBZ significantly inhibited glycolysis and cancer cell proliferation in vitro and in vivo by directly targeting HK2 with high potency and low toxicity, and can be developed as a novel HK2 small-molecule candidate drug for future cancer therapeutics.

Structure based discovery of novel hexokinase 2 inhibitors.

Hexokinase 2 (HK2) is over-expressed in most of human cancers and has been proved to be a promising target for cancer therapy. In this study, based on the structure of HK2, we screened over 6 millions of compounds to obtain the lead. A total of 26 (E)-N'-(2,3,4-trihydroxybenzylidene) arylhydrazide derivatives were then designed, synthesized, and evaluated for their HK2 enzyme activity and IC50 values against two cancer cell lines. Most of the 26 target compounds showed excellently in vitro activity. Among them, compound 3j showed the strongest inhibitory effects on HK2 enzyme activity with an IC50 of 0.53 ± 0.13 µM and exhibited the most potent growth inhibition against SW480 cells with an IC50 of 7.13 ± 1.12 µM, which deserves further studies.

Unusual ent-Labdane Diterpenoid Dimers and their Selective Activation of TRPV Channels.

Five unusual dimers of ent-labdane diterpenoids (1-5) were isolated and identified from Andrographis paniculata, a famous medicinal plant. Bisandrographolide E (1) represents the first example of a labdane dimer possessing an unprecedent tricyclic system that comprised a spiroketal moiety fused with a ketal-γ-lactone unit in its skeleton. Its biosynthetically related intermediates, all four stereoisomers at C-12 and C-15', bisandrographolides F (2, a new compound) and A-C (3-5), were obtained at the same time. The steric configurations of the newly formed asymmetric carbons in 1-5 were first solved by single-crystal X-ray diffraction of the diacetone derivatives of 2-4 and ECD and NMR calculations of 1. More importantly, bisandrographolides 1-5, with different chemical structures or absolute configurations at C-12 and C-15', selectively activated different TRPV1-4 channels and protected cardiomyocytes from hypoxia-reoxygenation injury. Among them, 5 with 12R/15'S configuration activated TRPV1 most effectively and displayed the best cardiomyocyte protection.

Meroterpenoids from Ganoderma sinense protect hepatocytes and cardiomyocytes from oxidative stress induced injuries.

Four meroterpenoids, applanatumols F (1), H (3), I (2), and lingzhiol (4) were isolated from the 95% EtOH extract of the fruiting bodies of Ganoderma sinense. Their structures were established on the basis of NMR spectroscopic analyses, optical rotatory dispersion data, ECD spectra, and X-ray crystallography. Compounds 1, 2, 4 existed as racemic mixtures ((+) 1a, 2a, 4a; (-) 1b, 2b, 4b), while 3 as a single enantiomer. Base on the seperated enantiomers, we sought to explicit possible effects of compounds 1-4 on hydrogen peroxide (H2O2)-induced cell death and to determine their underlying molecular mechanisms in human normal liver LO2 cells. Among them, compound 2a treatment effectively protected LO2 cells against H2O2-induced cell damage and apoptosis. H2O2 exposure increased ROS, which was inhibited by 2a treatment. Mitochondrial membrane potential decrease, nuclear fragments, caspase-3 activation and PARP cleavage were also arrested by 2a. Further, increased levels of Nrf2, HO-1, phosphorylation Akt and up-regulation of antioxidant enzymes were detected in 2a treated cells, indicating that the anti-oxidative effects of 2a might protect LO2 cells against oxidative damage via PI3K/Akt-mediated activation of Nrf2/HO-1 pathway. In addition, compound 2a showed potential protective role of cardiomyocyte from ischemia/reperfusion injury, and pretreatment with 2a could decrease CK and LDH levels and increase GSH level.

New natural inhibitors of hexokinase 2 (HK2): Steroids from Ganoderma sinense.

Hexokinase 2 (HK2), a rate-limiting enzyme in the first step of glycolysis pathway, expresses at high level in cancer cells compared with normal cells. HK2 provides a new target for cancer therapy due to its pivotal role in tumor tumourigenic and metastatic process. The structure-based virtual ligand screening in a small in-house database of natural products predicted that a new steroid, (22E,24R)-6ß-methoxyergosta-7,9(11),22-triene-3ß,5α-diol (2) from Ganoderma sinense has high binding affinity to HK2 with significant calculated binding free energy. Based on this prediction, compound 2, together with the other 12 steroid analogues (1, 3-13) from this plant were selected for further in vitro microscale thermophoresis (MST), enzyme inhibition, and cell-based assays based on the HK2 target. And compound 2 was finally identified as an HK2 inhibitor. As the first natural HK2 inhibitor, compound 2 can be considered as a potential drug candidate targeting at HK2 for cancer therapy.

Structure based discovery of clomifene as a potent inhibitor of cancer-associated mutant IDH1.

Isocitrate dehydrogenase (IDH) plays an indispensable role in the tricarboxylic acid cycle, and IDH mutations are present in nearly 75% of glioma and 20% of acute myeloid leukemia. One IDH1R132H inhibitor (clomifene citrate) was found by virtual screening method, which can selectively suppress mutant enzyme activities in vitro and in vivo with a dose-dependent manner. The molecular docking indicated that clomifene occupied the allosteric site of the mutant IDH1. Enzymatic kinetics also demonstrated that clomifene inhibited mutant enzyme in a non-competitive manner. Moreover, knockdown of mutant IDH1 in HT1080 cells decreased the sensitivity to clomifene. In vivo studies indicated that clomifene significantly suppressed the tumor growth of HT1080-bearing CB-17/Icr-scid mice with oral administration of 100 mg/kg and 50 mg/kg per day. In short, our findings highlight clomifene may have clinical potential in tumor therapies as a safe and effective inhibitor of mutant IDH1.

Benserazide, a dopadecarboxylase inhibitor, suppresses tumor growth by targeting hexokinase 2.

BACKGROUND: Hexokinase (HK) is the rate-limiting enzyme in the first reaction of glycolysis. And Hexokinase 2 (HK2) is most closely related to malignant tumor which expresses at higher level compared with normal cells. HK2 plays a pivotal role in tumor initiation and maintenance, which provides a new target for cancer therapy. METHODS: Structure-based virtual ligand screening was used in hit identification from ZINC Drug Database. Microscale thermophoresis assay was performed to evaluate the binding affinity. Enzyme inhibition, cytotoxicity, apoptosis, intracellular ATP level, mitochondrial membrane potential (MMP), glucose uptake and lactate production experiments were undertaken in SW480 cells to identify Benz as a HK2 inhibitor. Western blot was used to test protein expression. SW480 cells xenograft mouse models were used for in vivo study. Nano-particles of Benz were prepared to improve the antitumor efficacy and tumor targeting of Benz. HPLC was used to measure the concentration of free Benz in tumor tissues. RESULTS: Benserazide (Benz), was identified as a selective HK2 inhibitor, could specifically bind to HK2 and significantly inhibit HK2 enzymatic activity in vitro. In addition, Benz reduced glucose uptake, lactate production and intracellular ATP level, and could cause cell apoptosis and an increased loss of MMP as well. In vivo study indicated that intraperitoneal (ip) injection of Benz at 300 and 600 mg/Kg suppressed cancer growth in tumor-bearing mice and no toxicity shown. To further improve the antitumor efficacy and tumor targeting of Benz, nano-particles of Benz was prepared. Liposomal Benz at 100 and 200 mg/Kg performed potent inhibitory effects on tumor-bearing mice, showing reduced dose and better efficacy. CONCLUSIONS: Our study provides a new direction for the development of Benz and its analogues as novel antitumor agents for cancer therapy.

Proton pump inhibitor ilaprazole suppresses cancer growth by targeting T-cell-originated protein kinase.

T-cell-originated protein kinase (TOPK) is highly and frequently expressed in various cancer tissues and plays an indispensable role in the mitosis of cancer cells, and therefore, it is an important target for drug treatment of tumor. Ilaprazole was identified to be a potent TOPK inhibitor. The data indicated that ilaprazole inhibited TOPK activities with high affinity and selectivity. In vitro studies showed that ilaprazole inhibited TOPK activities in HCT116, ES-2, A549, SW1990 cancer cells. Moreover, knockdown of TOPK in these cells decreased their sensitivities to ilaprazole. Results of an in vivo study demonstrated that gavage of ilaprazole in HCT116 colon tumor-bearing mice effectively suppressed cancer growth. The TOPK downstream signaling molecule phospho-histone H3 in tumor tissues was also decreased after ilaprazole treatment. Our results suggested that ilaprazole inhibited the cancer growth by targeting TOPK both in vitro and in vivo.

A natural product from Cannabis sativa subsp. sativa inhibits homeodomain-interacting protein kinase 2 (HIPK2), attenuating MPP+-induced apoptosis in human neuroblastoma SH-SY5Y cells.

Homeodomain-interacting protein kinase 2 (HIPK2) is a conserved serine/threonine kinase, which regulate transcription, cell differentiation, proliferation and apoptosis. Previous evidences indicated that HIPK2 could be involved in the pathogenesis of neurodegenerative diseases, suggesting as a novel target for Parkinson's disease (PD) therapeutic development. Herein, gene microarray analysis was performed to verify the key regulatory function of HIPK2 in PD. (Z)-methylp-hydroxycinnamate (ZMHC, 7) with other eighteen compounds were isolated from Cannabis sativa subsp. sativa, growing in Bama Yao Autonomous County, one of the five largest longevity regions of the world. Intriguingly, ZMHC was identified to bind HIPK2 with high affinity through molecular modeling and molecular dynamics (MD) simulations. Moreover, cell morphology, flow cytometry and western blot assay suggested that ZMHC inhibited HIPK2, which attenuated MPP+-induced apoptosis in SH-SY5Y cells. In conclusion, these findings discovered a natural product that inhibited HIPK2, and highlighted that ZMHC could be a potential precursor agent for future PD therapy.

Stereo- and region-specific biotransformation of physapubescin by four fungal strains.

Biotransformations of physapubescin (1) were performed by four fungal strains-Mucor subtilissimus AS 3.2454, Mucor polymorphosporus AS 3.3443, Aspergillus niger AS 3.795, and Syncephalastrum racemosum AS 3.264. Four metabolites were prepared in the biotransformation process of 1, and their structures were elucidated as 15α-acetoxy-5,6ß:22,26:24,25-triepoxy-26α-hydroxy-3ß-methoxy 4ß-hydroxyergost-1-one (2), 15α-acetoxy-5,6ß:22,26-diepoxy-4ß,24ß,25α,26(α, ß)-tetrahydroxyergost-3ß-methoxy-1-one (3a/3b), 15α-acetoxy-5,6ß:22,26-diepoxy-4ß,24ß,25α,26(α, ß)-tetrahydroxyergost-2-en-1-one (4a/4b), and physapubescin D (5), by spectroscopic data analysis. Among them, metabolites 2 and 3 are new. All of these fungal strains showed the ability to be highly stereo- and region-specific for the bioconversion of substrate (1). Our research provides a reference for the structural derivatization of withanolides or possibly even other natural products.

Natural products as modulator of autophagy with potential clinical prospects.

Natural compounds derived from living organisms are well defined for their remarkable biological and pharmacological properties likely to be translated into clinical use. Therefore, delving into the mechanisms by which natural compounds protect against diverse diseases may be of great therapeutic benefits for medical practice. Autophagy, an intricate lysosome-dependent digestion process, with implications in a wide variety of pathophysiological settings, has attracted extensive attention over the past few decades. Hitherto, accumulating evidence has revealed that a large number of natural products are involved in autophagy modulation, either inducing or inhibiting autophagy, through multiple signaling pathways and transcriptional regulators. In this review, we summarize natural compounds regulating autophagy in multifarious diseases including cancer, neurodegenerative diseases, cardiovascular diseases, metabolic diseases, and immune diseases, hoping to inspire further investigation of the underlying mechanisms of natural compounds and to facilitate their clinical use for multiple human diseases.