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.

Penthorum chinense Pursh leaf tea debittering mechanisms via green tea manufacturing process and its influence on NAFLD-alleviation activities.

The green-tea manufacturing process showed good effect of flavor improving, debittering and shaping in making Penthorum chinensePursh leaf (PL) tea (PLT), which serves as a polyphenol dietary supplement and beverage raw material. GC-MS results showed that its unpleasant grassy odor decreased by 42.8% due to dodecanal, geranylacetone, and (E)-2-nonenal reduction, coupled with 1-hexadecanol increasing. UPLC-ESI-TOF-MS identified 95 compounds and showed that the debittering effect of green-tea manufacturing process was attributed to decreasing of flavonols and lignans, especially quercetins, kaempferols and luteolins, and increasing of dihydrochalcones which act as sweeteners bitterness-masking agents, while astringency was weakened by reducing delphinidin-3,5-O-diglucoside chloride, kaempferol-7-O-ß-d-glucopyranoside, and tannins. The increase of pinocembrins and catechins in aqueous extracts of PLT, maintained its hepatoprotective, NAFLD-alleviation, and hepatofibrosis-prevention activities similar to PL in high fat-diet C57BL/6 mice, with flavonoids, tannins, tannic acids, and some newfound chemicals, including norbergenin, gomisin K2, pseudolaric acid B, tanshinol B, as functional ingredients.

Effects of acupuncture treatment for myasthenia gravis: A systematic review and meta-analysis.

BACKGROUND: Randomized controlled trials (RCTs) of acupuncture for myasthenia gravis (MG) were searched and the efficacy of acupuncture in the treatment of MG was evaluated by meta-analysis. METHODS: We searched for RCTs in six main electronic databases, and collected RCTs of acupuncture treatment for MG from database creation to 28 February 2023. The main outcome was the effective rate and the secondary outcome was the Traditional Chinese Medicine (TCM) relative clinical score, absolute clinical score (ACS) of MG, Quantitive myasthenia gravis score (QMG), quality of life, and adverse events. Odds ratios (ORs) and weighted mean differences (WMD) and 95% confidence intervals (CI) were used to assess pooled effect estimates using Review Manager software. RESULTS: A total of 14 RCTs were included. Meta-analysis showed that the effective rate in the acupuncture group was significantly improved compared with conventional Western medicine alone [OR = 4.28, 95% CI (2.95, 6, 22), P<0.005]. The pooled WMDs revealed that TCM relative clinical score [WMD = -2.22, 95% CI = (-2.53, -1.90), P<0.005], ACS of MG [WMD = -3.14, 95% CI = (-3.67, -2.62), P<0.005], and QMG [WMD = -0.88, 95% CI = (-1.46, -0.29), P<0.005] in the acupuncture group was lower than the control group. Adverse reactions related to acupuncture and quality of life were less mentioned among included RCTs. CONCLUSION: This meta-analysis demonstrated that acupuncture as an auxiliary may play a positive role in treating MG. It can improve the effective rate of treatment, and reduce TCM relative clinical score, ACS of MG, and QMG. However, the quality of included studies was generally low and caution should be exercised when considering this treatment option. In the future, more rigorous study designs and high-quality RCTs are needed to verify the efficacy of acupuncture in the treatment of MG, because the results of high-quality RCTs are more reliable and accurate.

Oral magnesium prevents acetaminophen-induced acute liver injury by modulating microbial metabolism.

Acetaminophen overuse is a common cause of acute liver failure (ALF). During ALF, toxins are metabolized by enzymes such as CYP2E1 and transformed into reactive species, leading to oxidative damage and liver failure. Here, we found that oral magnesium (Mg) alleviated acetaminophen-induced ALF through metabolic changes in gut microbiota that inhibit CYP2E1. The gut microbiota from Mg-supplemented humans prevented acetaminophen-induced ALF in mice. Mg exposure modulated Bifidobacterium metabolism and enriched indole-3-carboxylic acid (I3C) levels. Formate C-acetyltransferase (pflB) was identified as a key Bifidobacterium enzyme involved in I3C generation. Accordingly, a Bifidobacterium pflB knockout showed diminished I3C generation and reduced the beneficial effects of Mg. Conversely, treatment with I3C or an engineered bacteria overexpressing Bifidobacterium pflB protected against ALF. Mechanistically, I3C bound and inactivated CYP2E1, thus suppressing formation of harmful reactive intermediates and diminishing hepatocyte oxidative damage. These findings highlight how interactions between Mg and gut microbiota may help combat ALF.

Sheng Mai Yin shows anti-fatigue, anti-hypoxia and cardioprotective potential in an experimental joint model of fatigue and acute myocardial infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiovascular disease (CVD) and fatigue are two common diseases endangering human life and health that may interact and reinforce one another. Myocardial infarction survivors frequently experience fatigue, and acute myocardial infarction (AMI) is one of the most common cardiovascular diseases that cause fatigue-induced sudden death. Sheng Mai Yin (SMY), a Chinese medicine prescription, is traditionally used for the treatment of diabetes and cardiovascular disease, and has been demonstrated to reduce fatigue and safeguard cardiac function. AIM OF THE STUDY: This study aims to investigate the effects and underlying mechanisms of SMY in treating fatigue and AMI. MATERIALS AND METHODS: The pharmacological mechanisms of SMY in treating fatigue and AMI were predicted by bioinformatics and network pharmacology methods. After administering SMY at high, medium and low doses, the swimming time to exhaustion, hemoglobin level, serological parameters and hypoxia tolerance time were detected in C57BL/6N mice, and the left ventricular ejection fractions (LVEF), left ventricular fractional shortening (LVFS), grasp strength, cardiac histopathology, serological parameters and the expression of PINK1 and Parkin proteins were examined in Wistar rats. RESULTS: 371 core targets for SMY and 282 disease targets for fatigue and AMI were obtained using bioinformatics and network pharmacology methods. Enrichment analysis of target genes revealed that SMY might interfere with fatigue and AMI through biological processes such as mitochondrial autophagy, apoptosis, and oxidative stress. For in vivo experiments, SMY showed significant anti-fatigue and hypoxia tolerance effects in mice; It also improved the cardiac function and grasp strength, decreased their cardiac index, myocardial injury and fibrosis degree, and induced serological parameters levels and the expression of PTEN-induced putative kinase 1 (PINK1) and Parkin proteins in myocardium, suggesting that SMY may exert cardioprotective effects in a joint rat model of fatigue and AMI by inhibiting excessive mitochondrial autophagy. CONCLUSION: This study revealed the anti-fatigue, anti-hypoxia and cardioprotective effects of SMY in a joint model of fatigue-AMI, and the pharmacological mechanism may be related to the inhibition of mitochondrial autophagy in cardiomyocytes through the PINK1/Parkin pathway. The discoveries may provide new ideas for the mechanism study of traditional Chinese medicine, especially complex prescriptions, in treating fatigue and AMI.

Cinobufotalin prevents bone loss induced by ovariectomy in mice through the BMPs/SMAD and Wnt/ß-catenin signaling pathways.

BACKGROUND: Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength. However, current anti-resorptive drugs carry a risk of various complications. The deep learning-based efficacy prediction system (DLEPS) is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes. This study aimed to explore the protective effect and potential mechanisms of cinobufotalin (CB), a traditional Chinese medicine (TCM), on bone loss. METHODS: DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis. Micro-CT, histological and morphological analysis were applied for the bone protective detection of CB, and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells (hBMMSCs) were also investigated. The underlying mechanism was verified using qRT-PCR, Western blot (WB), immunofluorescence (IF), etc. RESULTS: A safe concentration (0.25 mg/kg in vivo, 0.05 µM in vitro) of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs. Both BMPs/SMAD and Wnt/ß-catenin signaling pathways participated in CB-induced osteogenic differentiation, further regulating the expression of osteogenesis-associated factors, and ultimately promoting osteogenesis. CONCLUSION: Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss, further promoting osteogenic differentiation/function of hBMMSCs, with BMPs/SMAD and Wnt/ß-catenin signaling pathways involved.

Yunpi Tongbian Fang alleviates slow transit constipation induced by loperamide by regulating intestinal microbiota and short-chain fatty acids in rats.

Slow transit constipation (STC) is a prevalent chronic colonic dysfunction disease that significantly impairs the quality of life for affected individuals. Yunpi Tongbian Fang (YPTBF), a traditional Chinese medicine compound, has demonstrated promising clinical efficacy; however, its underlying mechanism remains elusive. In order to assess the laxative properties of YPTBF, which encompasses the influence on gut microbiota, gut metabolites, gut neurotransmitters, and colon histology, an oral administration of YPTBF was conducted for a duration of two consecutive weeks on STC rats induced by loperamide hydrochloride. The results showed that YPTBF improved the symptoms of STC, alleviated the decrease in total fecal volume and fecal water content caused by loperamide-induced constipation, restored intestinal transport function, and HE staining showed the recovery of pathological damage to the colon mucosa. In addition, YPTBF increased the concentrations of 5-HT and ACHE, while reducing the concentrations of VIP and NO. YPTBF adjusted the diversity and abundance of gut microbiota in STC rats, enabling the recovery of beneficial bacteria and promoting the production of acetic acid, propionic acid, and butyric acid. We found that YPTBF can improve constipation in STC rats, possibly by regulating the intestinal microbiota structure and improving SCFAs metabolism.

Plant-Derived Exosome-Like Nanovesicles: Current Progress and Prospects.

Exosomes are small extracellular vesicles, ranging in size from 30-150nm, which can be derived from various types of cells. In recent years, mammalian-derived exosomes have been extensively studied and found to play a crucial role in regulating intercellular communication, thereby influencing the development and progression of numerous diseases. Traditional Chinese medicine has employed plant-based remedies for thousands of years, and an increasing body of evidence suggests that plant-derived exosome-like nanovesicles (PELNs) share similarities with mammalian-derived exosomes in terms of their structure and function. In this review, we provide an overview of recent advances in the study of PELNs and their potential implications for human health. Specifically, we summarize the roles of PELNs in respiratory, digestive, circulatory, and other diseases. Furthermore, we have extensively investigated the potential shortcomings and challenges in current research regarding the mechanism of action, safety, administration routes, isolation and extraction methods, characterization and identification techniques, as well as drug-loading capabilities. Based on these considerations, we propose recommendations for future research directions. Overall, our review highlights the potential of PELNs as a promising area of research, with broad implications for the treatment of human diseases. We anticipate continued interest in this area and hope that our summary of recent findings will stimulate further exploration into the implications of PELNs for human health.

Iridium(III)-Based Infrared Two-Photon Photosensitizers: Systematic Regulation of Their Photodynamic Therapy Efficacy.

Cyclometalated iridium(III) complexes are of significant importance in the field of antitumor photodynamic therapy (PDT), whether they exist as single molecules or are incorporated into nanomaterials. Nevertheless, a comprehensive examination of the relationship between their molecular structure and PDT effectiveness remains awaited. The influencing factors of two-photon excited PDT can be anticipated to be further multiplied, particularly in relation to intricate nonlinear optical properties. At present, a comprehensive body of research on this topic is lacking, and few discernible patterns have been identified. In this study, through systematic structure regulation, the nitro-substituted styryl group and 1-phenylisoquinoline ligand containing YQ2 was found to be the most potent infrared two-photon excitable photosensitizer in a 4 × 3 combination library of cyclometalated Ir(III) complexes. YQ2 could enter cells via an energy-dependent and caveolae-mediated pathway, bind specifically to mitochondria, produce 1O2 in response to 808 nm LPL irradiation, activate caspases, and induce apoptosis. In vitro, YQ2 displayed a remarkable phototherapy index for both malignant melanoma (>885) and non-small-cell lung cancer (>1234) based on these functions and was minimally deleterious to human normal liver and kidney cells. In in vivo antitumor phototherapy, YQ2 inhibited tumor growth by an impressive 85% and could be eliminated from the bodies of mice with a half-life as short as 43 h. This study has the potential to contribute significantly to the development of phototherapeutic drugs that are extremely effective in treating large, profoundly located solid tumors as well as the understanding of the structure-activity relationship of Ir(III)-based PSs in PDT.

Effect of vitamin D3 supplementation in winter on physical performance of university students: a one-month randomized controlled trial.

BACKGROUND: There is epidemiological evidence which suggests an association between 25-hydroxyvitamin D [25(OH)D] levels and bone and muscle function; however, it is unclear whether vitamin D supplementation has an added benefit beyond bone health. Here, we investigated the effects of vitamin D3 supplementation (1 month) on physical performance in Chinese university students in winter. METHODS: One hundred and seventeen eligible subjects with 25(OH)D (19.2 ± 7.8 ng/mL) were randomly assigned to either vitamin D3 supplement (N = 56; 1000 IU/day) or the control (N = 61) group for 1 month. Pre- and post-measurements included: 1) serum levels of 25(OH)D; 2) musculoskeletal and pulmonary function [vertical jump height (VJH) and right handgrip strength (RHS), forced vital capacity (FVC), and forced expiratory volume at 1s (FEV1)]; 3) bone turnover markers [parathyroid hormone (PTH), n-terminal osteocalcin (N-MID), and calcium]; 4) hemoglobin-related parameters [hemoglobin (Hb), hematocrit (HCT), red blood cells (RBC), and red cell distribution width (RDW)]; 5) lipid parameters [total triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)]; 6) Fatigue-related indicators [serum creatine kinase (CK), lactate dehydrogenase (LDH), and total testosterone (T)]. In addition, aerobic capacity was assessed by measuring maximal oxygen uptake (VO2max) at baseline. RESULTS: During wintertime, supplementation with 1000 IU/d of vitamin D3 significantly increased serum 25(OH)D levels (from 18.85 ± 7.04 to 26.98 ± 5.88 ng/mL, p < 0.05), accompanied by a decrease of PTH (p < 0.05). However, vitamin D3 supplementation did not significantly impact the physical performance, serum lipid parameters, and bone turnover markers of students. Furthermore, 25(OH)D was found to be positively correlated with VJH and negatively correlated with PTH and TC at the beginning and end of the study (p < 0.05). In addition, the multiple linear regression analysis showed that 25(OH)D combined with athletic, gender, height, weight, Hb, and FVC could account for 84.0% of the VO2max value. CONCLUSIONS: The study demonstrated that one-month of 1000 IU/d of vitamin D3 supplementation during the winter had beneficial effects on 25(OH)D status and PTH. However, vitamin D3 intervention was not sufficient to improve physical performance. Furthermore, 25(OH)D levels combined with athletic, Hb and FVC could be a predictor of VO2max.

Effectiveness of acupuncture as auxiliary combined with Western medicine for epilepsy: a systematic review and meta-analysis.

Background: Although more and more clinical studies have shown that acupuncture as an auxiliary combined with Western medicine is effective in the treatment of patients with epilepsy, no systematic reviews of acupuncture as a treatment for epilepsy have been published. Hence, we conducted this meta-analysis to evaluate the effect of acupuncture treatment on patients with epilepsy. Methods: This study retrieved randomized controlled trials (RCTs) of acupuncture treatment for epilepsy from various electronic databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese BioMedical Literature Database, and Wangfang database. These studies evaluated the effectiveness of acupuncture as an auxiliary treatment combined with Western medicine for patients with epilepsy. The methodological quality of the studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. Results: A total of 17 RCTs involving a total of 1,389 participants were included. The results showed that acupuncture combined with Western medicine improved the effective rates of treatment (OR: 4.28; 95% CI: 3.04-6.02; p < 0.001), and reduced the seizure frequency of patients (SMD: -3.29; 95% CI: -3.51 to -3.07; p < 0.001) and the EEG discharge frequency (SMD: -5.58; 95% CI: -7.02 to -4.14; p < 0.001). Regarding the quality of life and adverse events, the acupuncture group was superior to the control group in improving the overall quality of life of patients with epilepsy (SMD: 14.41; 95% CI: 12.51-16.32; p < 0.001) and decreased adverse events (OR: 0.38; 95% CI: 0.23-0.63, p < 0.001). Conclusion: The results of the analysis suggested that acupuncture combined with Western medicine is probably helpful in patients with epilepsy, but strong supportive data are not yet available. Given that this study is based on a low to moderate evidence-based analysis, the conclusions should be viewed with caution. Systematic review registration: PROSPERO, identifier no. CRD42023409923.

Ccrl2-centred immune-related lncRNA-mRNA co-expression network revealed the local skin immune activation mechanism of moxibustion on adjuvant arthritis mice.

BACKGROUND: Moxibustion is an important external therapy of traditional medicine that operates on some acupoints on the skin and is usually used for immune-related diseases. However, whether the immune function of the skin, especially the immune-related lncRNAs, contributes to the mechanism of moxibustion remains unclear. METHODS: Adjuvant arthritis (AA) was induced by injection of Complete Freund's adjuvant (CFA) into the right hind paw of mice. Moxibustion was administered on the Zusanli (ST36) acupoint for 3 weeks. The alteration of foot volume and cytokine concentration in serum was used to evaluate the anti-inflammation effect of moxibustion. CD83 expression in the local skin of ST36 was measured by immunofluorescence staining. Transcriptome RNA sequencing (RNA-seq) and lncRNA-mRNA network analysis were performed to construct a moxibustion-induced Immune-related lncRNA-mRNA co-expression network. qRT-PCR was used to validate the RNA-seq data. RESULTS: Moxibustion at ST36 relieved the foot swelling, decreased the TNF-α and IL-1ß concentrations in serum, and obviously increased the CD83 expression at the local skin of ST36. A total of 548 differentially expressed lncRNAs and 520 linked mRNAs were screened out. The significantly and predominately enriched Go term was inflammatory and immune response, and the main pathways related to inflammatory and immune responses include Toll-like receptor, cytokine-cytokine receptor, and MAPK signaling. The immune-related lncRNA-mRNA co-expression network showed 88 lncRNAs and 36 mRNAs, and Ccrl2 is the central hub of this network. CONCLUSION: Local immune activation is significantly triggered by moxibustion in ST36 of AA mice. The Ccrl2-centered immune-related lncRNA-mRNA co-expression network would be a promising target for decoding the mechanism of moxibustion for immune-related diseases.

Identification of in vivo metabolites of Citri Sarcodactylis Fructus by UHPLC-Q/Orbitrap HRMS.

INTRODUCTION: Citri Sarcodactylis Fructus has the effects of relieving cough, removing phlegm, and reducing asthma, but little is known about the metabolic and distribution of its chemical constituents in vivo. Therefore, it is necessary to study the metabolism of Citri Sarcodactylis Fructus in vivo. OBJECTIVE: We aimed to (1) analyze the distribution of prototype compounds and metabolites of the chemical constituents of Citri Sarcodactylis Fructus in rat and (2) infer the metabolites and metabolic pathways of the chemical constituents. MATERIALS AND METHODS: A C18 column (3 × 100 mm, 2.6 µm) was used. The mobile phase was water containing 0.1% formic acid (eluent A) and acetonitrile containing 0.1% formic acid (eluent B) at a discharge rate of 0.3 mL/min. Mass spectra of biological samples were collected in electrospray ionization (ESI) positive ion mode in the m/z 100-1500 scan range. The obtained biological samples were then subjected to chemical analysis, including plasma, urine, feces, and heart, liver, spleen, lungs, kidneys, stomach, and small intestine tissues. Prototype compounds and metabolites were identified. RESULTS: In all, 40 prototype compounds and 78 metabolites, including 26 phase I metabolites and 52 phase II metabolites, were identified using UHPLC-Q/Orbitrap HRMS. Eight possible metabolic pathways (reduction, hydrolysis, dehydration, methylation, hydroxylation, sulfation, glucuronidation, and demethylation) were proposed. The prototype compounds were predominantly distributed in lung tissues. The metabolites were mainly distributed in plasma and kidney tissues. CONCLUSION: We systematically investigated the metabolites of Citri Sarcodactylis Fructus in vivo. We suggest metabolic pathways that might be relevant for further metabolic studies and screening of active ingredients of Citrus Sarcodactylis Fructus in vivo.

[Intervention effect of Chuanxiong-Chishao herb pair on circRNA/lncRNA expression profile in a myocardial infarction-atherosclerosis model].

This study aimed to explore the intervention effect of Chuanxiong-Chishao herb pair(CX-CS) on a myocardial infarction-atherosclerosis(MI-AS) mouse model and investigate its effect on the expression profile of circular RNAs(circRNAs)/long non-coding RNAs(lncRNAs) in ischemic myocardium and aorta. Sixty male ApoE~(-/-) mice were randomly assigned to a model group, high-, medium-, and low-dose CX-CS groups(7.8, 3.9, and 1.95 g·kg~(-1)), and a positive drug group(metoprolol 26 mg·kg~(-1) and simvastatin 5.2 mg·kg~(-1)), with 12 mice in each group. Male C57BL/6J mice were assigned to the sham group. The mice in the model group and the groups with drug intervention were fed on a high-fat diet for 10 weeks, followed by anterior descending coronary artery ligation. After that, the mice were fed on a high-fat diet for another two weeks to induce the MI-AS model. The mice in the sham group received normal feed, followed by sham surgery without coronary artery ligation. Mice in the groups with drug intervention received CX-CS or positive drug by gavage for four weeks from the 9th week of high-fat feeding, and those in the model group and the sham group received an equal volume of normal saline. Whole transcriptome sequencing was performed on the heart and aorta tissues of the medium-dose CX-CS group, the model group, and the sham group after administration. The results showed that the medium-and high-dose CX-CS groups showed improved cardiac function and reduced myocardial fibrosis area, and the medium-dose CX-CS group showed significantly reduced plaque area. CX-CS treatment could reverse the expression of circRNA＿07227 and circRNA＿11464 in the aorta of AS model and circRNA expression(such as circRNA＿11505) in the heart of the MI model. Differentially expressed circRNAs between the CX-CS-treated mice and the model mice were mainly enriched in lipid synthesis, lipid metabolism, lipid transport, inflammation, and angiogenesis in the aorta, and in angiogenesis, blood pressure regulation, and other processes in the heart. CX-CS treatment could reverse the expression of lncRNAs such as ENSMUST00000162209 in the aorta of the AS model and TCONS＿00002123 in the heart of the MI model. Differentially expressed lncRNAs between the CX-CS-treated mice and model mice were mainly enriched in lipid metabolism, angiogenesis, autophagy, apoptosis, and iron death in the aorta, and in angiogenesis, autophagy, and iron death in the heart. In summary, CX-CS can regulate the expression of a variety of circRNAs and lncRNAs, and its intervention mechanism in coronary heart disease may be related to the regulation of angiogenesis and inflammation in ischemic myocardium, as well as lipid metabolism, lipid transport, inflammation, angiogenesis in AS aorta.

Bleeding the Excited State Energy to the Utmost: Single-Molecule Iridium Complexes for In Vivo Dual Photodynamic and Photothermal Therapy by an Infrared Low-Power Laser.

A series of cyclometalated Ir(III) complexes with morpholine and piperazine groups are designed as dual photosensitizers and photothermal agents for more efficient antitumor phototherapy via infrared low-power laser. Their ground and excited state properties, as well as the structural effect on their photophysical and biological properties, are investigated by spectroscopic, electrochemical, and quantum chemical theoretical calculations. They target mitochondria in human melanoma tumor cells and trigger apoptosis related to mitochondrial dysfunction upon irradiation. The Ir(III) complexes, particularly Ir6, demonstrate high phototherapy indexes to melanoma tumor cells and a manifest photothermal effect. Ir6, with minimal hepato-/nephrotoxicity in vitro, significantly inhibits the growth of melanoma tumors in vivo under 808 nm laser irradiation by dual photodynamic therapy and photothermal therapy and can be efficiently eliminated from the body. These results may contribute to the development of highly efficient phototherapeutic drugs for large, deeply buried solid tumors.

6-Shogaol Inhibits the Cell Migration of Colon Cancer by Suppressing the EMT Process Through the IKKß/NF-κB/Snail Pathway.

6-Shogaol from ginger has anti-inflammatory, anti-oxidation and anti-cancer effects. Aim of the Study: To study the effects and possible mechanisms of 6-Shogaol on inhibiting the migration of colon cancer cells Caco2 and HCT116 and prove the effects on proliferation and apoptosis. Materials and methods: The cells were treated with 6-Shogaol at the concentrations of 20, 40, 60, 80, and 100 µM, the cytotoxicity was tested by Colony formation assays and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and the Western blot was used to evaluate IKKß/NF-κB/Snail pathway and EMT-related proteins. In addition, in order to eliminate the interference of proliferation inhibition on the experiment, Caco2 cells were treated with 6-Shogaol at the concentrations of 0, 40, and 80 µM, HCT116 cells were treated with 6-Shogaol at the concentrations of 0, 20, and 40 µM, apoptosis was measured by Annex V/PI staining, and migration was measured by Wound healing assays and Transwell test. Results: 6-Shogaol significantly inhibited the growth of cells. The maximum inhibitory concentration of half of them was 86.63 µM in Caco2 cells and 45.25 µM in HCT116 cells. At 80 µM and 40 µM concentrations, 6-Shogaol significantly promoted apoptosis of colon cancer Caco2 cells and HCT116 cells, and also significantly inhibited cell migration (P < .05). In addition, Western blot analysis showed that at 80 µM dose of 6-Shogaol significantly reduced MMP-2, N-cadherin, IKKß, P-NF-κB and Snail expression in Caco2 cells (P < .05). 40 µM dose of 6-Shogaol significantly reduced VEGF, IKKß, and P-NF-κB expression, and MMP-2, N-cadherin and Snail was significantly decreased at 60 µM of 6-Shogaol in HCT116 cells(P < .05). However, there was no significant change in E-cadherin in Caco2 cells, and the expression of E-cadherin protein in HCT116 cells decreased. Conclusion: This study proposes and confirms that 6-Shogaol can significantly inhibit the migration of colon cancer cells Caco2 and HCT116, and its mechanism may be produced by inhibiting EMT through IKKß/NF-κB/Snail signaling pathway. It was also confirmed that 6-Shogaol inhibited the proliferation and promoted apoptosis of Caco2 and HCT116 cells.

Effect of traditional Chinese medicine monomers interfering with quorum-sensing on virulence factors of extensively drug-resistant Acinetobacter baumannii.

The antimicrobial resistance of Acinetobacter baumannii (A. baumannii) clinical isolates has emerged as a great threat to public health. Quorum sensing (QS) is one of the resistance mechanisms for drug-resistant A. baumannii. Interfering with QS is a promising strategy to combat infections caused by drug-resistant bacteria. This study explored the QS inhibition ability of thirty-four traditional Chinese medicine monomers (TCMMs) and assessed the effect of QS inhibitors (QSIs) on the virulence factors of twelve extensively drug-resistant A. baumannii (XDRAB) strains. Nine traditional Chinese medicine monomers, such as caffeic acid, cinnamic acid, and myricetin, were found to be able to inhibit the bacterial QS. Then, at 1/8 of the minimal inhibitory concentration, we found that these QSIs inhibited extensively drug-resistant A. baumannii adhesion and biofilm formation and downregulated the expression levels of virulence-associated genes (abaI, abaR, csuE, pgaA, and bap). In conclusion, nine traditional Chinese medicine monomers have QS inhibitory activity and may downregulate QS genes to interfere with the QS system, which could inhibit the expression of extensively drug-resistant A. baumannii virulence factors. These results suggest that traditional Chinese medicine monomers could develop as novel anti-virulence compounds to control extensively drug-resistant A. baumannii infections.

Pinellia ternata-containing traditional Chinese medicine combined with 5-HT3RAs for chemotherapy-induced nausea and vomiting: A PRISMA-compliant systematic review and meta-analysis of 22 RCTs.

BACKGROUND: Pinellia ternata (P. ternata, Banxia)-containing traditional Chinese medicine (TCM) is widely used in China as an adjuvant treatment for chemotherapy-induced nausea and vomiting (CINV). However, evidence of its efficacy and safety remains limited. PURPOSE: To investigate the efficacy and safety of P. ternata-containing TCM combined with 5-hydroxytryptamine-3 receptor antagonists (5-HT3RAs) in the treatment of CINV. STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: All relevant RCTs were systematically retrieved from seven internet databases (up to February 10, 2023). P. ternata-containing TCM combined with 5-HT3RAs to treat CINV was included in all RCTs. The clinical effective rate (CER) was defined as the primary outcome, while appetite, quality of life (QOL), and side effects were secondary outcomes. RESULTS: The meta-analysis included 22 RCTs with 1,787 patients. Our results indicated that P. ternata-containing TCM combined with 5-HT3RAs significantly improved the CER of CINV (RR = 1.46, 95% CI = 1.37-1.57, p < 0.00001), appetite (RR = 1.77, 95% CI = 1.42-2.20, p < 0.00001), QOL (RR = 7.67, 95% CI = 1.56-13.78, p = 0.01), the CER of several 5-HT3RA medications (RR = 1.47, 95% CI = 1.37-1.57, p < 0.00001), and acute and delayed vomiting (RR = 1.23, 95% CI = 1.12-1.36, p < 0.0001) compared with the 5-HT3RAs alone, while the combination therapy decreased the incidence of side effects induced by 5-HT3RAs for CINV (RR = 0.50, 95% CI = 0.42-0.59, p < 0.00001). CONCLUSION: According to the findings of this systematic review and meta-analysis, P. ternata-containing TCM combined with 5-HT3RAs was safer and more effective than 5-HT3RAs alone for CINV patients. However, due to the limitations of the included studies, more high-quality clinical trials are required to further validate our findings.

Research on Mechanisms of Chinese Medicines in Prevention and Treatment of Postoperative Adhesion.

Postoperative adhesion (PA) is currently one of the most unpleasant complications following surgical procedures. Researchers have developed several new strategies to alleviate the formation of PA to a great extent, but so far, no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention. Chinese medicine (CM) has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine. Therefore, this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments, including their pharmacological effects, therapeutic mechanisms and advantages in PA prevention. We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.

Role of traditional Chinese medicine in ameliorating mitochondrial dysfunction via non-coding RNA signaling: Implication in the treatment of neurodegenerative diseases.

Neurodegenerative diseases (NDs) are common chronic disorders associated with progressive nervous system damage, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, among others. Mitochondria are abundant in various nervous system cells and provide a bulk supply of the adenosine triphosphate necessary for brain function, considered the center of the free-radical theory of aging. One common feature of NDs is mitochondrial dysfunction, which is involved in many physiopathological processes, including apoptosis, inflammation, oxidative stress, and calcium homeostasis. Recently, genetic studies revealed extensive links between mitochondrion impairment and dysregulation of non-coding RNAs (ncRNAs) in the pathology of NDs. Traditional Chinese medicines (TCMs) have been used for thousands of years in treating NDs. Numerous modern pharmacological studies have demonstrated the therapeutic effects of prescription, herbal medicine, bioactive ingredients, and monomer compounds of TCMs, which are important for managing the symptoms of NDs. Some highly effective TCMs exert protective effects on various key pathological features regulated by mitochondria and play a pivotal role in recovering disrupted signaling pathways. These disrupted signaling pathways are induced by abnormally-expressed ncRNAs associated with mitochondrial dysfunction, including microRNAs, long ncRNAs, and circular RNAs. In this review, we first explored the underlying ncRNA mechanisms linking mitochondrial dysfunction and neurodegeneration, demonstrating the implication of ncRNA-induced mitochondrial dysfunction in the pathogenesis of NDs. The ncRNA-induced mitochondrial dysfunctions affect mitochondrial biogenesis, dynamics, autophagy, Ca2+ homeostasis, oxidative stress, and downstream apoptosis. The review also discussed the targeting of the disease-related mitochondrial proteins in NDs and the protective effects of TCM formulas with definite composition, standardized extracts from individual TCMs, and monomeric compounds isolated from TCM. Additionally, we explored the ncRNA regulation of mitochondrial dysfunction in NDs and the effects and potential mechanisms of representative TCMs in alleviating mitochondrial pathogenesis and conferring anti-inflammatory, antioxidant, and anti-apoptotic pathways against NDs. Therefore, this review presents an overview of the role of mitochondrion-related ncRNAs and the target genes for TCM-based therapeutic interventions in NDs, providing insight into understanding the "multi-level compound-target-pathway regulatory" treatment mechanism of TCMs.