Artemisinin and its derivatives as promising therapies for autoimmune diseases.

Artemisinin, a traditional Chinese medicine with remarkable antimalarial activity. In recent years, studies demonstrated that artemisinin and its derivatives (ARTs) showed anti-inflammatory and immunoregulatory effects. ARTs have been developed and gradually applied to treat autoimmune and inflammatory diseases. However, their role in the treament of patients with autoimmune and inflammatory diseases in particular is less well recognized. This review will briefly describe the history of ARTs use in patients with autoimmune and inflammatory diseases, the theorized mechanisms of action of the agents ARTs, their efficacy in patients with autoinmmune and inflammatory diseases. Overall, ARTs have numerous beneficial effects in patients with autoimmune and inflammatory diseases, and have a good safety profile.

The association between physical exercise behavior and psychological resilience of teenagers: an examination of the chain mediating effect.

The health of young people is crucial for the future and development of a nation. It is the collective responsibility and imperative mission of society to ensure the holistic well-being, both physically and mentally, of young individuals. Therefore, it is essential to thoroughly comprehend the factors that influence their health in order to expedite the exploration of effective solutions. The objective of this study is to comprehend the mechanisms that underlie the correlation between physical exercise behavior and psychological resilience among teenagers, while also examining the mediating role played by social sensitivity and need to belong. So put forward the hypothesis: (1) physical exercise behavior can positively predict the psychological resilience. (2) Social sensitivity and need to belong plays a mediating role between physical exercise behavior and psychological resilience. (3) Social sensitivity and need to belong plays a chain mediating role between physical exercise behavior and psychological resilience. Using the cluster sampling method, a total of 1106 students (with an average age of 15.7 and a standard deviation of 0.598) who met the requirements were surveyed from Shandong Province in China. Standard scales were utilized to assess Physical Exercise Behavior, Psychological Resilience, Social Sensitivity, and Need to Belong. For data analysis, Pearson's correlation analysis and bias-corrected percentile Bootstrap method were sequentially conducted. (1) The present study did not find any significant methodological bias, and the observed correlations between physical exercise behavior, psychological resilience, social sensitivity, and need to belong were all statistically significant; (2) Based on the self-determination theory, this study elucidates the relationship between physical exercise behavior and psychological resilience among teenagers. The findings indicate that physical exercise behavior positively predicts the need to belong and psychological resilience, while negatively predicting social sensitivity. Similarly, social sensitivity negatively predicts the need to belong and psychological resilience. Moreover, the need to belong directly and positively predicts psychological resilience. Importantly, all hypotheses proposed in this paper were empirically supported. (3) The indirect effect of the path mediated by social sensitivity is 0.009, while the indirect effect of the path mediated by need to belong is 0.033. Additionally, the combined indirect effect of both social sensitivity and need to belong as mediating variables is 0.014. (4) The cumulative sum of all these indirect effects amounts to 0.056. Based on the self-determination theory, we propose a chain mediation model, specially, physical exercise behavior can significantly positively predict psychological resilience, among which, social sensitivity and need to belong play a significant mediating role between Physical exercise behavior and psychological resilience. In addition, the adoption of good physical exercise behavior can enhance the psychological resilience of adolescents by diminishing social sensitivity and augmenting the need to belong.

Bithiophene-Functionalized Infrared Two-Photon Absorption Metal Complexes as Single-Molecule Platforms for Synergistic Photodynamic, Photothermal, and Chemotherapy.

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin-resistant non-small cell lung cancer tumors, with a 100 % survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two-photon activatable metal complex may contribute to a new generation of single-molecule-based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors.

Association of vitamin D with HIV infected individuals, TB infected individuals, and HIV-TB co-infected individuals: a systematic review and meta-analysis.

Background: Vitamin D deficiency (VDD) is a worldwide disease. VDD is also associated with an increased risk of HIV-related comorbidities and mortality, and patients have a tendency to develop active tuberculosis compared to those with latent tuberculosis infection. Vitamin D supplementation may modulate HIV replication, improve TB inflammation and reduce progression of HIV-TB co-infection. Methods: We meta-analyzed individual participant data from cohort studies, cross-sectional study, and RCTs of vitamin D in HIV group, TB group, and HIV-TB group. The primary outcomes were differences in vitamin D level and VDD prevalence between three groups, the secondary outcomes were CD4 count, HIV viral load, time to sputum smear conversion, time to culture conversion, relapse, morality, and TB score. Results: For vitamin D levels, the overall mean difference (MD) between HIV group and TB group was -0.21 (95% CI, -20.80-20.38; p = 0.9, I2 = 84%), HIV group and HIV-TB group was 0.87 (95% CI, -11.45-13.20; p = 0.89, I2 = 87%), and TB group and HIV-TB group was 1.17 (95% CI, -5.21-7.55; p = 0.72, I2 = 85%). For vitamin D deficiency prevalence, the overall odds ratio (OR) for HIV group versus TB group was 1.23 (95% CI, 0.46-3.31; p = 0.68; I2 = 70%), HIV group versus HIV-TB group was 1.53 (95% CI, 1.03-2.29; p = 0.04; I2 = 0%), and TB group versus HIV-TB group was 0.85 (95% CI, 0.61-1.20; p = 0.36; I2 = 22%). In HIV-TB group, the overall OR for vitamin D group versus placebo group was 0.78 (95% CI, 0.34-1.67; p = 0.52; I2 = 60%). Conclusion: Our findings indicated that there were no variations in vitamin D levels between three groups. The prevalence of vitamin D deficiency was higher in the HIV-TB group than in the HIV group. Additionally, the administration of vitamin D supplements did not have obvious impact on CD4 count and viral load. Likewise, vitamin D had no effect on time to sputum smear conversion, time to culture conversion, relapse, 12-month morality, and TB score.

Suitable Isolation Side Chains: A Simple Strategy for Simultaneously Improving the Phototherapy Efficacy and Biodegradation Capacities of Conjugated Polymer Nanoparticles.

Utilizing one molecule to realize combinational photodynamic and photothermal therapy upon single-wavelength laser excitation, which relies on a multifunctional phototherapy agent, is one of the most cutting-edge research directions in tumor therapy owing to the high efficacy achieved over a short course of treatment. Herein, a simple strategy of "suitable isolation side chains" is proposed to collectively improve the fluorescence intensity, reactive oxygen species production, photothermal conversion efficiency, and biodegradation capacity. Both in vitro and in vivo results reveal the practical value and huge potential of the designed biodegradable conjugated polymer PTD-C16 with suitable isolation side chains in fluorescence image-guided combinational photodynamic and photothermal therapy. These improvements are achieved through manipulation of aggregated states by only side chain modification without changing any conjugated structure, providing new insight into the design of biodegradable high-performance phototherapy agents.

Inhibitory effect of acupoint electrostimulation with different layers and intensities on muscular inflammatory pain and spinal WDR neuron activity. / ç©´ä½ä¸åŒå±‚æ¬¡å’Œå¼ºåº¦ç”µåˆºæ¿€ç¼“è§£è‚Œè‚‰ç‚Žæ€§ç—›åŠå¯¹è„Šé«“èƒŒè§’å¹¿åŠ¨åŠ›ç¥žç»å ƒçš„æŠ‘åˆ¶ä½œç”¨.

OBJECTIVES: To observe the analgesic effects of different levels and intensities of electrical stimulation on the local acupoints in the pain source area and their impact on wide dynamic range (WDR) neurons in the spinal dorsal horn, in order to provide a basis for selecting appropriate parameters for electroacupuncture (EA) stimulation. METHODS: Wistar rats were used in 3 parts of the experiment. Complete Freund's adjuvant was used to establish a model of inflammation-induced pain in the gastrocnemius muscle. After modeling, 6 rats were randomly selected for multi-channel extracellular electrophysiological recording of the electrical activity of WDR neurons, to determine the threshold for activating the A-component (Ta) and the C-component (Tc), which were used as the intervention intensities for skin transcutaneous electrical acupoint stimulation (TEAS) or EA. Thirty-six rats were randomly divided into normal , model , TEAS-Ta , TEAS-Tc, EA-Ta , and EA-Tc groups, with 6 rats in each group. In the pain source area , Ta or Tc intensity of TEAS or EA intervention at"Chengshan"(BL57) was performed for 30 min each time, once a day, for 3 consecutive days. A small animal pressure pain measurement instrument was used to measure the mechanical pressure pain threshold of the gastrocnemius muscle in rats, and the Von Frey filament was used to measure the mechanical pain threshold of the footpad. Thirteen rats were randomly selected to observe the immediate responsiveness of WDR neurons to Ta/Tc intensity of EA or TEAS in BL57. RESULTS: The thresholds of TEAS to activate WDR neuron A-component or C-component were (2.43±0.57) mA and (7.00±1.34) mA, respectively, while the thresholds for EA to activate muscle WDR neuron A-component or C-component were (0.72±0.34) mA and (1.58±0.35) mA, respectively. After injection of CFA into the gastrocnemius muscle, compared with the normal group both the mechanical pressure pain threshold of the gastrocnemius muscle and the mechanical pain threshold of the footpad of rats in the model group were significantly decreased (P<0.001). After TEAS-Ta, TEAS-Tc or EA-Ta intervention in the BL57, both the mechanical pressure pain threshold of the gastrocnemius muscle and the mechanical pain threshold of the footpad were significantly higher than those in the model group (P<0.05, P<0.001). Compared with the normal group, the electrical threshold for evoking WDR neuron C-component discharge was significantly decreased (P<0.001) in the model group, while increased after TEAS-Ta, TEAS-Tc, or EA-Ta intervention (P<0.01) compared with the model group. The evoked discharge frequency of muscle WDR neurons decreased significantly after immediate intervention with TEAS-Ta, TEAS-Tc, or EA-Ta (P<0.01, P<0.05). EA-Tc had no significant improvement on the evoked electrical activity of WDR neurons or pain behavior. CONCLUSIONS: TEAS-Ta, TEAS-Tc, or EA-Ta can all alleviate the local and footpad mechanical pain in rats with muscle inflammation and inhibit the responsiveness of WDR neurons, indicating that different intensities are required for analgesic effects at different levels of acupoints in the pain source area.

Tongxinluo Activates PI3K/AKT Signaling Pathway to Inhibit Endothelial Mesenchymal Transition and Attenuate Myocardial Fibrosis after Ischemia-Reperfusion in Mice.

OBJECTIVE: To investigate the potential role of Tongxinluo (TXL) in attenuating myocardial fibrosis after myocardial ischemia-reperfusion injury (MIRI) in mice. METHODS: A MIRI mouse model was established by left anterior descending coronary artery ligation for 45 min. According to a random number table, 66 mice were randomly divided into 6 groups (n=11 per group): the sham group, the model group, the LY-294002 group, the TXL group, the TXL+LY-294002 group and the benazepril (BNPL) group. The day after modeling, TXL and BNPL were administered by gavage. Intraperitoneal injection of LY-294002 was performed twice a week for 4 consecutive weeks. Echocardiography was used to measure cardiac function in mice. Masson staining was used to evaluate the degree of myocardial fibrosis in mice. Qualitative and quantitative analysis of endothelial mesenchymal transition (EndMT) after MIRI was performed by immunohistochemistry, immunofluorescence staining and flow cytometry, respectively. The protein expressions of platelet endothelial cell adhesion molecule-1 (CD31), α-smoth muscle actin (α-SMA), phosphatidylinositol-3-kinase (PI3K) and phospho protein kinase B (p-AKT) were assessed using Western blot. RESULTS: TXL improved cardiac function in MIRI mice, reduced the degree of myocardial fibrosis, increased the expression of CD31 and inhibited the expression of α-SMA, thus inhibited the occurrence of EndMT (P<0.05 or P<0.01). TXL significantly increased the protein expressions of PI3K and p-AKT (P<0.05 or P<0.01). There was no significant difference between TXL and BNPL group (P>0.05). In addition, the use of the PI3K/AKT pathway-specific inhibitor LY-294002 to block this pathway and combination with TXL intervention, eliminated the protective effect of TXL, further supporting the protective effect of TXL. CONCLUSION: TXL activated the PI3K/AKT signaling pathway to inhibit EndMT and attenuated myocardial fibrosis after MIRI in mice.

A Versatile Nanovaccine Enhancement Strategy Based on Suction-Inspired Physical Therapy.

Vaccine technology is effective in preventing and treating diseases, including cancers and viruses. The efficiency of vaccines can be improved by increasing the dosage and frequency of injections, but it would bring an extra burden to people. Therefore, it is necessary to develop vaccine-boosting techniques with negligible side effects. Herein, we reported a cupping-inspired noninvasive suction therapy that could enhance the efficacy of cancer/SARS-CoV-2 nanovaccines. Negative pressure caused mechanical immunogenic cell death and released endogenous adjuvants. This created a subcutaneous niche that would recruit and activate antigen-presenting cells. Based on this universal central mechanism, suction therapy was successfully applied in a variety of nanovaccine models, which include prophylactic/therapeutic tumor nanovaccine, photothermal therapy induced in situ tumor nanovaccine, and SARS-CoV-2 nanovaccine. As a well-established physical therapy method, suction therapy may usher in an era of noninvasive and high-safety auxiliary strategies when combined with vaccines.

Comparative analysis of medicinal plants Scutellaria baicalensis and common adulterants based on chloroplast genome sequencing.

BACKGROUND: Scutellaria baicalensis Georgi has been extensively used as a medicinal herb in China for over 2000 years. They may be intentionally or inadvertently substituted or blended with comparable species in the local market, threatening clinical medication safety. Molecular markers are effective tools to prevent misidentification and eliminate doping and falsification among Scutellaria plants. This study screened four highly variable regions to identify Scutellaria and its adulterants. In addition, a phylogenetic analysis was performed using the complete cp genome combined with published Scutellaria species samples. Moreover, a comparative analysis of the cp genomes was conducted to investigate the cp genome evolution of S. baicalensis. RESULTS: The complete cp genome of five species of Scutellaria was sequenced for the first time, and four previously published Scutellaria species were re-sequenced. They all exhibited a conserved quadripartite structure in their cp genomes, including two distinct regions, namely a small and large single copy region, respectively, and two inverted repeats encompassing the majority of ribosomal RNA genes. Furthermore, the nine species exhibited high conservation from aspects of the genome structure, codon usage, repeat sequences, and gene content. Four highly variable regions (matK-rps16, ndhC-trnV-UAC, psbE-petL, and rps16-trnQ-UUG) may function as potential molecular markers for differentiating S. baicalensis from its adulterants. Additionally, the monophyly of Scutellaria was ascertained and could be reclassified into two subgenera, subgenus Anaspis and subgenus Scutellaria, as evidenced by the phylogenetic analyses on sequences of cp genome and shared protein-coding sequences. According to the molecular clock analysis, it has been inferred that the divergence of Scutellaria occurred at approximately 4.0 Mya during the Pliocene Epoch. CONCLUSION: Our study provides an invaluable theoretical basis for further Scutellaria species identification, phylogenetics, and evolution analysis.

The Beneficial Effects of Dietary Astragali Radix Are Related to the Regulation of Gut Microbiota and Its Metabolites.

Astragali Radix (AR) or its extract has been used as an herbal medicine and dietary supplement in China, Europe, and the United States. The gut microbiota could provide new insights for exploring dietary supplements' underlying mechanism on organisms. However, no reports have focused on the regulatory effect of AR on the gut microbiota as a dietary supplement. In this study, healthy ICR mice of either sex were divided into AR and control (CON) groups and given AR water extract (4.55 mg/kg·day-1) or saline by gavage for 14 days, respectively. Then 16S rRNA gene sequencing and ultra-high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry-based fecal metabolomics were integrated to investigate the benefits of dietary AR. Weighted gene coexpression network analysis was also introduced to investigate the metabolites with highly synergistic changes. AR supplementation influenced the structure of intestinal microflora, especially enriching short-chain fatty acid-producing bacteria g_Coprobacillus, g_Prevotella, and g_Parabacteroides. AR also significantly altered the fecal metabolome, mainly related to amino acid metabolism, nucleotide metabolism, and bile acid (BA) metabolism. Moreover, the increased secondary BAs and BA-sulfates might closely relate to intestinal microflora. These findings provide valuable insights for future research of dietary AR as a functional food.

Effects of processing technology on tea quality analyzed using high-resolution mass spectrometry-based metabolomics.

Fixation is a crucial step in green tea processing that can impact quality. In this study, we explored the differences in the chemical components of steamed and fried green teas made from the same batch of fresh tea leaves using different fixing methods. Results showed that concentrations of sucrose and free amino acids were significantly higher in steamed green tea. Abundances of 12 compounds including purine nucleoside, pyrimidine nucleoside derivatives, and catechins were higher in fried green tea, while 34 compounds such as amino acids and their derivatives, benzofurans and flavonoids were higher in steamed green tea. Thus, steaming retained more compounds associated with sweet and fresh tastes, such as free amino acids, while frying produced more compounds with bitter tastes, such as catechin. This might explain why steamed green tea is mellower than fried tea.

Species discrimination of multiple botanical origins of Fritillaria species based on infrared spectroscopy, thin layer chromatography-image analysis and untargeted metabolomics.

BACKGROUND: Fritillaria Bulbus (FB), a precious medicinal herb renowned for its heat-clearing, lung-moistening, cough-relieving and phlegm-eliminating effects. In pursuit of profits, unscrupulous merchants have engaged in the substitution or adulteration of valuable varieties with cheaper alternatives. It is, therefore, urgent to develop effective technical approaches to identify FBs from adulterants. METHODS: This paper employed infrared spectroscopy (IR), thin layer chromatography-image analysis (TLC-IA), and untargeted metabolomics techniques to discriminate ten species of FBs. RESULTS: Five species of FBs were successfully differentiated using mid-infrared spectroscopy. Furthermore, the power of TLC-IA technology allowed the differentiation of five species of FBs and two origins of FCBs (Fritillariae Cirrhosae Bulbus). Remarkably, through the application of untargeted metabolomics technique, the precise discrimination of five species of FBs, as well as three origins of FCBs were accomplished. Moreover, a comprehensive identification of 101 markers that reliably distinguished diverse FBs was achieved through the employment of untargeted metabolomics technique. CONCLUSION: The investigation presented powerful means of detection for assuring the quality control of Fritillaria herbs.

Short-Term Effect of Rose Bengal Photodynamic Therapy (RB-PDT) on Collagen I, Collagen V, NF-κB, LOX, TGF-ß and IL-6 Expression of Human Corneal Fibroblasts, In Vitro.

PURPOSE: To investigate collagen I, collagen V, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), lysyl oxidase (LOX), transforming growth factor ß1 (TGF-ß1) and interleukin-6 (IL-6) expression in healthy and keratoconus human corneal fibroblasts (HCFs and KC-HCFs), 24 h after Rose Bengal photodynamic therapy (RB-PDT). METHODS: HCFs were isolated from healthy human corneal donors (n = 5) and KC-HCFs from elective penetrating keratoplasties (n = 5). Both cell cultures underwent RB-PDT (0.001% RB concentration, 0.17 J/cm2 fluence) and 24 h later collagen I, collagen V, NF-κB, LOX, TGF-ß1 and IL-6 mRNA and protein expression have been determined using qPCR and Western blot, IL-6 concentration in the cell culture supernatant by ELISA. RESULTS: TGF-ß1 mRNA expression was significantly lower (p = 0.02) and IL-6 mRNA expression was significantly higher in RB-PDT treated HCFs (p = 0.01), than in HCF controls. COL1A1, COL5A1 and TGF-ß1 mRNA expression was significantly lower (p = 0.04; p = 0.02 and p = 0.003) and IL-6 mRNA expression was significantly higher (p = 0.02) in treated KC-HCFs, than in KC-HCF controls. TGF-ß1 protein expression in treated HCFs was significantly higher than in HCF controls (p = 0.04). IL-6 protein concentration in the HCF and KC-HCF culture supernatant after RB-PDT was significantly higher than in controls (p = 0.02; p = 0.01). No other analyzed mRNA and protein expression differed significantly between the RB-PDT treated and untreated groups. CONCLUSIONS: Our study demonstrates that RB-PDT reduces collagen I, collagen V and TGF-ß1 mRNA expression, while increasing IL-6 mRNA and protein expression in KC-HCFs. In HCFs, RB-PDT increases TGF-ß1 and IL-6 protein level after 24 h.

Human corneal epithelial cell and fibroblast migration and growth factor secretion after rose bengal photodynamic therapy (RB-PDT) and the effect of conditioned medium.

PURPOSE: To investigate human corneal epithelial cell and fibroblast migration and growth factor secretion after rose bengal photodynamic therapy (RB-PDT) and the effect of conditioned medium (CM). METHODS: A human corneal epithelial cell line (HCE-T), human corneal fibroblasts (HCF) and keratoconus fibroblasts (KC-HCF) have been used. Twenty-four hours after RB-PDT (0.001% RB concentration, 565 nm wavelength illumination, 0.17 J/cm2 fluence) cell migration rate using scratch assay and growth factor concentrations in the cell culture supernatant using ELISA have been determined. In addition, the effect of CM has been observed. RESULTS: RB-PDT significantly reduced migration rate in all cell types, compared to controls (p≤0.02). Migration rate of HCE-T cultures without RB-PDT (untreated) was significantly higher using HCF CM after RB-PDT, than using HCF CM without RB-PDT (p<0.01). Similarly, untreated HCF displayed a significantly increased migration rate with HCE-T CM after RB-PDT, compared to HCE-T CM without treatment (p<0.01). Furthermore, illumination alone and RB-PDT significantly decreased keratinocyte growth factor (KGF) concentration in HCF and KC-HCF supernatant, and RB-PDT significantly decreased soluble N-Cadherin (SN-Cad) concentration in HCF supernatant, compared to controls (p<0.01 for all). In HCE-T CM, RB-PDT increased hepatocyte growth factor (HGF) and basic fibroblast growth factor (FGFb) concentration (p≤0.02), while decreasing transforming growth factor ß (TGF-ß) concentration (p<0.01). FGFb concentration increased (p<0.0001) and TGF-ß concentration decreased (p<0.0001) in HCF CM, by RB-PDT. Epidermal growth factor (EGF), HGF, and TGF-ß concentration decreased (p≤0.03) and FGFb concentration increased (p<0.01) in KC-HCF CM, using RB-PDT. CONCLUSIONS: HCE-T, HCF and KC-HCF migration rate is reduced 24 hours after RB-PDT. In contrast, HCE-T migration is enhanced using HCF CM after RB-PDT, and HCF migration rate is increased through HCE-T CM following RB-PDT. Modulation of EGF, KGF, HGF, FGFb, TGF-ß and N-Cadherin secretion through RB-PDT may play an important role in corneal wound healing.

Research progress of traditional Chinese medicine in improving hepatic fibrosis based on inhibiting pathological angiogenesis.

Hepatic fibrosis is the formation of scar tissue in the liver. This scar tissue replaces healthy liver tissue and can lead to liver dysfunction and failure if left untreated. It is usually caused by chronic liver disease, such as hepatitis B or C, alcohol abuse, or non-alcoholic fatty liver disease. Pathological angiogenesis plays a crucial role in the development of hepatic fibrosis by promoting the growth of new blood vessels in the liver. These new vessels increase blood flow to the damaged areas of the liver, which triggers the activation of hepatic stellate cells (HSCs). HSCs are responsible for producing excess collagen and other extracellular matrix proteins that contribute to the development of fibrosis. Pathological angiogenesis plays a crucial role in the development of hepatic fibrosis by promoting the growth of new blood vessels in the liver. These new vessels increase blood flow to the damaged areas of the liver, which triggers the activation of HSCs. HSCs are responsible for producing excess collagen and other extracellular matrix proteins that contribute to the development of fibrosis. Traditional Chinese medicine (TCM) has been found to target pathological angiogenesis, thereby providing a potential treatment option for hepatic fibrosis. Several studies have demonstrated that TCM exhibits anti-angiogenic effects by inhibiting the production of pro-angiogenic factors, such as vascular endothelial growth factor and angiopoietin-2, and by reducing the proliferation of endothelial cells. Reviewing and highlighting the unique TCM recognition of treating hepatic fibrosis by targeting pathological angiogenesis may shed light on future hepatic fibrosis research.

A Case of Pseudohypoparathyroidism Misdiagnosed as Idiopathic Epilepsy for 5 Years: Clinical Analysis and Follow-up Outcomes.

We report a 15-year-old Chinese girl who presented with intermittent seizure episodes and had been misdiagnosed as having idiopathic epilepsy 5 years previously. Laboratory testing revealed hypocalcemia, hyperphosphatemia, and a high parathyroid hormone (PTH) concentration. She was subsequently shown to have pseudohypoparathyroidism type Ib (PHPIb) based on the results of methylation analysis of the GNAS gene, which showed a loss of methylation of the differentially methylated regions (DMR) of GNAS-AS1, GNAS-XL, and GNAS-A/B; and a gain of methylation of the DMR of the GNAS-NESP55 region. We adjusted the patient's medication by prescribing calcium and calcitriol supplements, and gradually reduced the doses of antiepileptic drugs, until they had been completely discontinued. As a result, the patient did not experience any further seizures or epileptiform symptoms; and had normal plasma calcium, phosphorus, and 25-hydroxyvitamin D concentrations and 24-hour urinary calcium excretion. In addition, her PTH concentration gradually normalized over 12 months, and no urinary stones were found on ultrasonographic examination. In conclusion, the clinical presentation of PHP is complex, and the condition is often misdiagnosed. The diagnosis and follow-up of the present patient have provide valuable insights that should contribute to informed clinical decision-making and the implementation of appropriate treatment strategies.

Progress on traditional Chinese medicine in improving hepatic fibrosis through inhibiting oxidative stress.

Hepatic fibrosis is a common pathological process that occurs in the development of various chronic liver diseases into cirrhosis and liver cancer, characterized by excessive deposition of the extracellular matrix. In the past, hepatic fibrosis was thought to be a static and irreversible pathological process. In recent years, with the rapid development of molecular biology and the continuous in-depth study of the liver at the microscopic level, more and more evidence has shown that hepatic fibrosis is a dynamic and reversible process. Therefore, it is particularly important to find an effective, simple, and inexpensive method for its prevention and treatment. Traditional Chinese medicine (TCM) occupies an important position in the treatment of hepatic fibrosis due to its advantages of low adverse reactions, low cost, and multi-target effectiveness. A large number of research results have shown that TCM monomers, single herbal extracts, and TCM formulas play important roles in the prevention and treatment of hepatic fibrosis. Oxidative stress (OS) is one of the key factors in the occurrence and development of hepatic fibrosis. Therefore, this article reviews the progress in the understanding of the mechanisms of TCM monomers, single herbal extracts, and TCM formulas in preventing and treating hepatic fibrosis by inhibiting OS in recent years, in order to provide a reference and basis for drug therapy of hepatic fibrosis.

Electroacupuncture improves cognitive dysfunction in rats with Alzheimer's disease by regulating microglial cells. / ç”µé’ˆé€šè¿‡è°ƒæŽ§å°èƒ¶è´¨ç»†èƒžæ”¹å–„é˜¿å°”èŒ¨æµ·é»˜ç— å¤§é¼ è®¤çŸ¥åŠŸèƒ½éšœç¢çš„æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on microglia (MG), Janus kinase-2 (JAK2) and signal transducer and activator of transcription-3 (STAT3) in hippocampal CA1 region of Alzheimer's di-sease (AD) rats, so as to explore its mechanisms in the treatment of AD. METHODS: Thirty-six male SD rats were randomly divided into sham operation, model and EA groups, with 12 rats in each group. The AD rat model was established by intraperitoneal injection of D-galactose combined with intrahippocampal injection of aggregated Aß25-35. The rats in the EA group were given EA (2 Hz/20 Hz, 2 mA) at "Baihui"(GV20) and"Shenting"(GV24) for 30 min, once daily, 6 days a week for 4 weeks. Morris water maze test was used to detect the learning and memory ability and spatial exploration ability of rats. HE staining was used to observe the pathological changes of hippocampus. The ultrastructure of hippocampal neurons was observed by transmission electron microscopy. The positive expression of MG marker io-nized calcium adaptor protein (Iba-1) in hippocampus was observed by immunofluorescence staining. The expression levels of serum inflammatory factor interferon-γ (IFN-γ) and transforming growth factor beta 1 (TGF-ß1) were detected by ELISA. The mRNA expression levels of JAK2, STAT3, inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1) in hippocampal CA1 region were detected by real-time quantitative PCR. The protein and phosphorylation levels of JAK2 and STAT3 in hippocampal CA1 region were detected by Western blot. RESULTS: Compared with the sham operation group, the escape latency of the model group was significantly prolonged (P<0.01), and the number of crossing the original platform was significantly reduced (P<0.01), the positive expression of Iba-1 in CA1 region, the content of serum IFN-γ, the relative mRNA expressions of JAK2, STAT3 and iNOS, and the protein and phosphorylation levels of JAK2 and STAT3 were significantly increased (P<0.01), while the content of serum TGF-ß1 and the relative expression of Arg-1 mRNA were significantly decreased (P<0.01). Compared with the model group, the escape latency of rats in the EA group was significantly shortened (P<0.01), the number of crossing the original platform was significantly increased (P<0.01), the positive expression of Iba1, the content of serum IFN-γ, the mRNA expressions of JAK2, STAT3 and iNOS, and the protein and phosphorylation levels of JAK2 and STAT3 were significantly decreased (P<0.05, P<0.01), while the content of serum TGF-ß1 and the expression of Arg-1 mRNA were significantly increased (P<0.01). Moreover, pathological and ultrastructural observation showed a reduction in the number of hippocampal neurons, changement of nuclear morphology, dilation of intercellular space, and decreased number of mitochondria in the model group；these situations were relatively milder in the EA group. CONCLUSIONS: EA can improve the learning and memory function of AD rats, which may be associated with its functions in decreasing MG activities, and inhibiting the JAK2 / STAT3 signaling pathway in the hippocampus.

Chromosome-level genomes of three key Allium crops and their trait evolution.

Allium crop breeding remains severely hindered due to the lack of high-quality reference genomes. Here we report high-quality chromosome-level genome assemblies for three key Allium crops (Welsh onion, garlic and onion), which are 11.17 Gb, 15.52 Gb and 15.78 Gb in size with the highest recorded contig N50 of 507.27 Mb, 109.82 Mb and 81.66 Mb, respectively. Beyond revealing the genome evolutionary process of Allium species, our pathogen infection experiments and comparative metabolomic and genomic analyses showed that genes encoding enzymes involved in the metabolic pathway of Allium-specific flavor compounds may have evolved from an ancient uncharacterized plant defense system widely existing in many plant lineages but extensively boosted in alliums. Using in situ hybridization and spatial RNA sequencing, we obtained an overview of cell-type categorization and gene expression changes associated with spongy mesophyll cell expansion during onion bulb formation, thus indicating the functional roles of bulb formation genes.

Therapeutic potential of Lianhua Qingke in airway mucus hypersecretion of acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Lianhua Qingke (LHQK) is an effective traditional Chinese medicine used for treating acute tracheobronchitis. In this study, we evaluated the effectiveness of LHQK in managing airway mucus hypersecretion in the acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: The AECOPD model was established by subjecting male Wistar rats to 12 weeks of cigarette smoke (CS) exposure (80 cigarettes/day, 5 days/week for 12 weeks) and intratracheal lipopolysaccharide (LPS) exposure (200 µg, on days 1, 14, and 84). The rats were divided into six groups: control (room air exposure), model (CS + LPS exposure), LHQK (LHQK-L, LHQK-M, and LHQK-H), and a positive control group (Ambroxol). H&E staining, and AB-PAS staining were used to evaluate lung tissue pathology, inflammatory responses, and goblet cell hyperplasia. RT-qPCR, immunohistochemistry, immunofluorescence and ELISA were utilized to analyze the transcription, expression and secretion of proteins related to mucus production in vivo and in the human airway epithelial cell line NCI-H292 in vitro. To predict and screen the active ingredients of LHQK, network pharmacology analysis and NF-κB reporter system analysis were employed. RESULTS: LHQK treatment could ameliorate AECOPD-triggered pulmonary structure damage, inflammatory cell infiltration, and pro-inflammatory cytokine production. AB-PAS and immunofluorescence staining with CCSP and Muc5ac antibodies showed that LHQK reduced goblet cell hyperplasia, probably by inhibiting the transdifferentiation of Club cells into goblet cells. RT-qPCR and immunohistochemistry of Muc5ac and APQ5 showed that LHQK modulated mucus homeostasis by suppressing Muc5ac transcription and hypersecretion in vivo and in vitro, and maintaining the balance between Muc5ac and AQP5 expression. Network pharmacology analysis and NF-κB luciferase reporter system analysis provided insights into the active ingredients of LHQK that may help control airway mucus hypersecretion and regulate inflammation. CONCLUSION: LHQK demonstrated therapeutic effects in AECOPD by reducing inflammation, suppressing goblet cell hyperplasia, preventing Club cell transdifferentiation, reducing Muc5ac hypersecretion, and modulating airway mucus homeostasis. These findings support the clinical use of LHQK as a potential treatment for AECOPD.