Artemisia argyi extract subfraction exerts an antifungal effect against dermatophytes by disrupting mitochondrial morphology and function / 中国天然药物

Artemisia argyi (A. argyi), a plant with a longstanding history as a raw material for traditional medicine and functional diets in Asia, has been used traditionally to bathe and soak feet for its disinfectant and itch-relieving properties. Despite its widespread use, scientific evidence validating the antifungal efficacy of A. argyi water extract (AAWE) against dermatophytes, particularly Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum gypseum, remains limited. This study aimed to substantiate the scientific basis of the folkloric use of A. argyi by evaluating the antifungal effects and the underlying molecular mechanisms of its active subfraction against dermatophytes. The results indicated that AAWE exhibited excellent antifungal effects against the three aforementioned dermatophyte species. The subfraction AAWE6, isolated using D101 macroporous resin, emerged as the most potent subfraction. The minimum inhibitory concentrations (MICs) of AAWE6 against T. rubrum, M. gypseum, and T. mentagrophytes were 312.5, 312.5, and 625 μg·mL-1, respectively. Transmission electron microscopy (TEM) results and assays of enzymes linked to cell wall integrity and cell membrane function indicated that AAWE6 could penetrate the external protective barrier of T. rubrum, creating breaches ("small holes"), and disrupt the internal mitochondrial structure ("granary"). Furthermore, transcriptome data, quantitative real-time PCR (RT-qPCR), and biochemical assays corroborated the severe disruption of mitochondrial function, evidenced by inhibited tricarboxylic acid (TCA) cycle and energy metabolism. Additionally, chemical characterization and molecular docking analyses identified flavonoids, primarily eupatilin (131.16 ± 4.52 mg·g-1) and jaceosidin (4.17 ± 0.18 mg·g-1), as the active components of AAWE6. In conclusion, the subfraction AAWE6 from A. argyi exerts antifungal effects against dermatophytes by disrupting mitochondrial morphology and function. This research validates the traditional use of A. argyi and provides scientific support for its anti-dermatophytic applications, as recognized in the Chinese patent (No. ZL202111161301.9).

Classic mechanisms and experimental models for the anti-inflammatory effect of traditional Chinese medicine.

Inflammation is a common disease involved in the pathogenesis, complications, and sequelae of a large number of related diseases, and therefore considerable research has been directed toward developing anti-inflammatory drugs for the prevention and treatment of these diseases. Traditional Chinese medicine (TCM) has been used to treat inflammatory and related diseases since ancient times. According to the review of abundant modern scientific researches, it is suggested that TCM exhibit anti-inflammatory effects at different levels, and via multiple pathways with various targets, and recently a series of in vitro and in vivo anti-inflammatory models have been developed for anti-inflammation research in TCM. Currently, the reported classic mechanisms of TCM and experimental models of its anti-inflammatory effects provide reference points and guidance for further research and development of TCM. Importantly, the research clearly confirms that TCM is now and will continue to be an effective form of treatment for many types of inflammation and inflammation-related diseases.

N-butanol extract of Hedyotis diffusa protects transgenic Caenorhabditis elegans from Aß-induced toxicity.

Hedyotis diffusa Willd (Rubiaceae) is a widely used and resourceful traditional Chinese medicine that exerts protection against aging and age-related diseases. However, the underlying mechanisms of the protective effects remain largely unclear. Alzheimer's disease (AD) is an age-related neurodegenerative disease, of which ß-amyloid (Aß)-induced toxicity has been suggested as a main cause. Herein, we use the transgenic Caenorhabditis elegans CL4176, CL2006, and CL2355 strains, which express human Aß1-42 peptide, to investigate the effects and the possible mechanisms of n-butanol extract of H.diffusa (HDB)-mediated protection against Aß toxicity in vivo. During the experiments, a method of quality control for HDB was established by HPLC. Additionally, we examined the effects of HBD on gene expression changes with qRT-PCR, aggregation of Aß plagues with thioflavin-S staining, and protein detection with GFP labeling. HDB improved lifespan, locomotion, and stress resistance. Further study showed that HDB decreased paralysis, the accumulation of ROS, and AChE activity. Moreover, HDB suppressed neuronal Aß-expression-induced defects in chemotaxis behavior and increased SOD activity. HDB also downregulated the Aß mRNA level and decreased the number of Aß deposits. Furthermore, HDB increased the expression levels of sod-3, daf-16, hsf-1, and hsp-16.2 gene and upregulated hsp-16.2::GFP and gst-4::GFP expression. Taken together, these results suggest that HDB may protect against Aß-induced toxicity in C. elegans via the insulin/insulin-like growth factor-1 (IGF-1) signaling pathway.

Preclinical efficacy against acute myeloid leukaemia of SH1573, a novel mutant IDH2 inhibitor approved for clinical trials in China

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults, with increasing incidence with age and a generally poor prognosis. Almost 20% of AML patients express mutant isocitrate dehydrogenase 2 (mIDH2), which leads to the accumulation of the carcinogenic metabolite 2-hydroxyglutarate (2-HG), resulting in poor prognosis. Thus, global institutions have been working to develop mIDH2 inhibitors. SH1573 is a novel mIDH2 inhibitor that we independently designed and synthesised. We have conducted a comprehensive study on its pharmacodynamics, pharmacokinetics and safety. First, SH1573 exhibited a strong selective inhibition of mIDH2 R140Q protein, which could effectively reduce the production of 2-HG in cell lines, serum and tumors of an animal model. It could also promote the differentiation of mutant AML cell lines and granulocytes in PDX models. Then, it was confirmed that SH1573 possessed characteristics of high bioavailability, good metabolic stability and wide tissue distribution. Finally, toxicological data showed that SH1573 had no effects on the respiratory system, cardiovascular system and nervous system, and was genetically safe. This research successfully promoted the approval of SH1573 for clinical trials (CTR20200247). All experiments demonstrated that, as a potential drug against mIDH2 R140Q acute myeloid leukaemia, SH1573 was effective and safe.

Effects of oxygen at varied concentrations on in vitro maturation of human immature oocytes and early-stage development of embryos / 实用医学杂志

Objective To determine the effects of oxygen at varied concentrations on in vitro maturation (IVM)of oocytes,and subsequent fertilization,early-stage development of embryos by collecting the human imma-ture oocytes from assisted reproduction treatment. Methods Immature oocytes were randomly allocated to be cul-tured with oxygen at a lower or higher concentration. Intracytoplasmic sperm injection of mature oocytes after IVM , the rates of maturation,fertilization,embryo cleavage and high quality embryo were investigated. Results The GV oocytes cultured with oxygen at the lower concentration yielded higher maturation and fertilization rates than those at the higher concentration(P<0.05). There were no significant differences in the rates of embryo cleavage and high quality embryo between two groups(P > 0.05). For MI oocytes,the maturation rate of oocytes cultured with oxygen at the lower concentration was higher as compared to that at the higher concertration (P < 0.05). There were no significant differences in the rates of fertilization ,embryo cleavage and high quality embryo between the two groups(P > 0.05). Conclusions Oxygen at a lower concentration is beneficial to IVM of human imma-ture oocytes and it also improves the fertilization of GV oocytes after IVM. Oxygen at a lower concentration has no beneficial effect on the embryo cleavage rate and high quality embryo rate.

Effects of oxygen at varied concentrations on in vitro maturation of human immature oocytes and early-stage development of embryos / 实用医学杂志

Objective To determine the effects of oxygen at varied concentrations on in vitro maturation (IVM)of oocytes,and subsequent fertilization,early-stage development of embryos by collecting the human imma-ture oocytes from assisted reproduction treatment. Methods Immature oocytes were randomly allocated to be cul-tured with oxygen at a lower or higher concentration. Intracytoplasmic sperm injection of mature oocytes after IVM , the rates of maturation,fertilization,embryo cleavage and high quality embryo were investigated. Results The GV oocytes cultured with oxygen at the lower concentration yielded higher maturation and fertilization rates than those at the higher concentration(P<0.05). There were no significant differences in the rates of embryo cleavage and high quality embryo between two groups(P > 0.05). For MI oocytes,the maturation rate of oocytes cultured with oxygen at the lower concentration was higher as compared to that at the higher concertration (P < 0.05). There were no significant differences in the rates of fertilization ,embryo cleavage and high quality embryo between the two groups(P > 0.05). Conclusions Oxygen at a lower concentration is beneficial to IVM of human imma-ture oocytes and it also improves the fertilization of GV oocytes after IVM. Oxygen at a lower concentration has no beneficial effect on the embryo cleavage rate and high quality embryo rate.

Preliminary evaluation of median nerve by high-frequency ultrasound in patients with diabetic polyneuropathy / 中华超声影像学杂志

Objective To explore the feasibility of high-frequency ultrasound detecting median nerve (MN) in type 2 diabetes mellitus(T2DM)with diabetic peripheral neuropathy(DPN).Methods Forty-two healthy volunteers were included as control group(Group A).Eighty-eight T2DM patients were divided into two groups according to symptoms,signs and electrophysiological results:with DPN (group C,46 patients) and without DPN (Group B,42 patients).The width(W),thickness(T) and cross-sectional area(CSA) of MN at 6 points [the wrist crease,pisiform bone,hamate bone,the 6 cm proximal to the wrist crease,the 4 cm proximal to tip of the medial epicondyle(ME) and the midpoint of the humerus] were evaluated.ROC curve was plotted to determine clinical diagnostic value of three lines on six points in diagnosis of DPN. Results ①Comparing with Group A,the width(P <0.05) except for the 4 cm proximal to tip of ME and the midpoint of the humerus,the thickness (P <0.05) except for the 4 cm distal to ME and CSAs of all points were enlarged in DPN patients(P <0.001).The width(P <0.05)at the wrist crease,hamate bone and the midpoint of the humerus,the thickness (P <0.01) at the wrist crease and pisiform bone,CSAs (P <0.01) of all sites except for the wrist crease were increased in Group B.Comparing Group B with C, the width at the wrist crease,the thickness in the midpoint of the humerus,CSAs except for the 4 cm proximal to ME and the midpoint of the humerus were dramaticlly increased in Group C(P <0.001).②A diagnostic value comparison:when diagnostic value of W,T and CSA at six points is the most predictive, the sensitivity is 80.4%,84.8%,84.8% respectively and specificities are all 54.8%.Diagnostic value of CSA and T is superior to the width.The CSA and T of the hamate bone level were the most predictive of DPN.The corresponding optimal cut-off value was 0.097 cm 2 ,0.233 cm respectively.Conclusions The backbone and the abnormal changes of different lines of the MN in DPN can be observed by high-frequency ultrasound.The width and thickness of the MN at six points are increased in different degree,but CSAs of all levels can enlarge.When diagnostic value of W,T and CSA at six points is the most predictive for DPN, the sensitivity is superior to specificity respectively.The CSA and T of the hamate bone levelare the most predictive for the evaluation of DPN.