The effectiveness of fire needle therapy in the treatment of recurrent aphthous stomatitis: A systematic review and meta-analysis.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is common in clinical practice and imposes both physical and psychological distress on patients. OBJECTIVE: This study aimed to evaluate the clinical effectiveness of fire needle therapy for the treatment of RAS, providing a basis for clinical decision-making. METHODS: Eight databases, in both Chinese and English, were searched from their inception until December 2022. All randomized controlled trials (RCTs) that utilized fire needle therapy, either alone or combined with other treatments for RAS, were considered. Data evaluation and extraction were conducted independently by 2 authors. RESULTS: The revised Cochrane Risk of Bias Version 2 tool was employed to assess the risk of bias in the included RCTs. A meta-analysis was conducted using Review Manager 5.4 and Stata 15.0. Nine RCTs involving 1469 patients were selected for inclusion. The meta-analysis revealed that, compared to a non-fire-needle control group (primarily utilizing vitamin and transfer factor treatments), fire needle therapy for RAS significantly improved the total effective rate (relative risk = 1.25, 95% confidence interval [CI] [1.14, 1.36], P < .00001), reduced the visual analogue scale score (mean difference = -1.68, 95% CI [-1.82, -1.53], P < .0001), diminished the Traditional Chinese Medicine symptom score (standardized mean difference = -1.20, 95% CI [-1.76, -0.65], P < .0001), and shortened the healing time (mean difference = -1.66, 95% CI [-2.73, -0.59], P = .002). Notably, there was no significant difference in the recurrence rate between the groups (relative risk = -0.18, 95% CI [-0.36, 0.01], P = .06). Further subgroup analysis on total efficacy rate was performed based on variables such as experimental group intervention, control group intervention, and duration of therapy to explore potential sources of heterogeneity. CONCLUSION: Fire needle therapy appears to be a clinically effective treatment for RAS, offering benefits such as pain alleviation, symptom improvement based on the Traditional Chinese Medicine parameters, and faster recovery. Nonetheless, the overall quality of the RCTs available raises concerns. Future research, involving high-quality RCTs, is essential to confirm the clinical efficacy and safety of this treatment. Registration number: PROSPERO (CRD42023387973).

Bazi Bushen alleviates skin senescence by orchestrating skin homeostasis in SAMP6 mice.

Bazi Bushen, a Chinese-patented drug with the function of relieving fatigue and delaying ageing, has been proven effective for extenuating skin senescence. To investigate the potential mechanism, senescence-accelerated mouse prone 6 (SAMP6) was intragastrically administered with Bazi Bushen for 9 weeks to induce skin homeostasis. Skin homeostasis is important in mitigating skin senescence, and it is related to many factors such as oxidative stress, SASP, apoptosis, autophagy and stem cell. In our study, skin damage in SAMP6 mice was observed using HE, Masson and SA-ß-gal staining. The content of hydroxyproline and the activities of SOD, MDA, GSH-PX and T-AOC in the skin were measured using commercial assay kits. The level of SASP factors (IL-6, IL-1ß, TNF-α, MMP2 and MMP9) in skin were measured using ELISA kits. The protein expressions of p16, p21, p53, Bax, Bcl-2, Cleaved caspase-3, LC3, p62, Beclin1, OCT4, SOX2 and NANOG were measured by western blotting. The expression of ITGA6 and COL17A1 was measured by immunofluorescence staining and western blotting. Our findings demonstrated that Bazi Bushen alleviated skin senescence by orchestrating skin homeostasis, reducing the level of oxidative stress and the expression of SASP, regulating the balance of apoptosis and autophagy and enhancing the protein expressions of ITGA6 and COL17A1 to improve skin structure in SAMP6 mice. This study indicated that Bazi Bushen could serve as a potential therapy for alleviating skin senescence.

Development of a highly sensitive immunoassay for detecting aminopyrine abuse in herbal tea.

With the popularity of herbal tea in China, many food fraudsters have added illegal drugs to herbal tea to enhance its functions, among which aminopyrine is widely abused as an antipyretic and analgesic. Presently, there is no immunoassays for aminopyrine, and it is difficult to achieve real-time detection in the field. Based on a polyclonal antibody of aminopyrine with high specificity and sensitivity, an optimal combination of coating antigen/antibody was obtained by screening different coating antigens. On this basis, a sensitive ic-ELISA method was established to detect aminopyrine in herbal tea. The detection limit of the ic-ELISA was 0.18 ng mL-1, which was much lower than the 100 ng mL-1 required as a standard. The method had good consistency with LC-MS in the detection of actual samples and could be used as a reliable method for the detection of aminopyrine in herbal tea.

Developing an ultrasensitive immunochromatographic assay for authentication of an emergent fraud aminopyrine in herbal tea.

Aminopyrine is a nonsteroidal anti-inflammatory drug only for medical purposes, however, it has been illegally added in traditional Chinese herbal teas for fraud activity recently. In this study, a specific antibody against aminopyrine with IC50 of 3.00 ng/mL was obtained for the first time by a rational hapten design. Furthermore, an ultrasensitive gold nanoparticles immunochromatographic assay (AuNPs-ICA) for determination of aminopyrine based on a portable reader was firstly developed, with cut-off value of 100.00 ng/mL, limit of detection (LOD) of 4.80 ng/mL and limit of quantification (LOQ) of 5.71 ng/mL for herbal tea, respectively. The recovery rates ranged from 93.21 % to 105.61 %, with inter-assay coefficient of variation (CV) from 1.08 % to 3.82 %. Additionally, 24 blind samples were examined simultaneously by AuNPs-ICA and LC-MS/MS, demonstrating a good consistency for each other. The proposed AuNPs-ICA is an ultrasensitive and reliable tool for on-site surveillance screening of fraud additives in herbal tea.

One-step ultra-sensitive immunochromatographic strip authenticating an emergent fraud acetophenetidin in herbal tea.

Herbal tea is a highly popular and widely consumed beverage. However, a pain-relieving and fever-reducing drug, acetophenetidin, was recently found to illegally occur in herbal tea for a fraud purpose. Due to the potential health risk and urgent requirement for on-site screening method, a one-step and high specificity strip for identifying acetophenetidin was developed for the first time. Assisted by computational chemistry, four haptens were designed to prepare immunogens and coating antigens for antibody generation, and a specific antibody with ultra-sensitivity and high specificity was generated, showing half maximal inhibitory (IC50) of 16.46 ng/mL for acetophenetidin, less than 3.5% of cross-reactivity to analogs by ELISA. A gold nanoparticles immunochromatographic strip was developed for detection of acetophenetidin in herbal tea, demonstrating a cut-off value of 160 ng/mL and a limit of detection of 1.63 ng/mL. The recovery rates were ranged from 102.2% to 106.1% with coefficient of variation between 2.21% and 7.20%. The analysis of real samples (n = 20) by the strip was well correlated with that of the confirmatory method, liquid chromatography-tandem mass spectrometry. The proposed strip has the potential to be used for rapid screening of acetophenetidin in herbal tea.

Integrating 16S sequencing and metabolomics study on anti-rheumatic mechanisms against collagen-induced arthritis of Wantong Jingu Tablet.

Wantong Jingu Tablet (WJT), a mixture of traditional Chinese medicine, was reported to relieve the symptoms of rheumatoid arthritis (RA), but its pharmacological mechanism was not completely understood. The aim of this study was to investigate the therapeutic mechanisms of WJT for RA in vivo. The effects of WJT on joint pathology, as well as the levels of Bax, Bcl-2, caspase-3, cleaved-caspase-3, ERK1/2, pERK1/2, TNF-α, IL-1ß, and IL-6 were measured using collagen-induced arthritis (CIA) rats. The intestinal flora composition and the metabolites alteration were analyzed by 16S rDNA sequencing and metabolomics method, respectively. We found that WJT ameliorated the severity of the CIA rats which might be mediated by inducing apoptosis, inactivating the MEK/ERK signals and reducing the production of pro-inflammatory cytokines. WJT, in part, relieved the gut microbiota dysbiosis, especially bacterial phylum Bacteroidetes, Tenericutes and Deferribacteres, as well as bacterial genus Vibrio, Macrococcus and Vagococcus. 3'-N-debenzoyl-2'-deoxytaxol, tubulysin B, and magnoline were significantly associated with the specific genera. We identified serotonin, glutathione disulfide, N-acetylneuraminic acid, naphthalene and thromboxane B2 as targeted molecules via metabolomics. Our findings contributed to the understanding of RA pathogenesis, and WJT played essential roles in gut microbiota health and metabolite modulation in the CIA rats.

Identification of drug targets and potential molecular mechanisms for Wantong Jingu Tablet extract in treatment of rheumatoid arthritis: bioinformatics analysis of fibroblast-like synoviocytes.

BACKGROUND: Rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLSs) play important roles in pathogenesis of rheumatoid arthritis (RA). Wantong Jingu Tablet (WJT), a mixture of traditional Chinese medicine, is a potentially effective therapy for RA, but its underlying mechanism is unclear. In this study, we explore the effects of WJT on human RA-FLSs and the underlying molecular mechanism. METHODS: The major components of WJT were determined using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Cell proliferative ability was evaluated by CCK-8, colony formation assay, and EdU incorporation assay. Cell apoptotic capacity was examined by caspase-3 and caspase-9 activity test. Protein levels of Bax and Bcl-2 were investigated by western blotting. High-throughput sequencing and bioinformatics analysis were conducted to screen and identify targeted genes, followed by identification by qRT-PCR and western blotting. RESULTS: In this study, we have identified 346 compounds in WJT. Our results showed that WJT inhibited the RA-FLSs proliferation, and promoted apoptosis in a dose- and time-dependent manner. More importantly, 184 differentially expressed genes (DEGs) has been screened after WJT treatment based on DEGSeq2 and 278 DEGs was identified by DEGSeq2 combined with WGCNA. Then, 10 hub genes were identified based on two different analyses, while the expression levels of only SMC3, THOC1, BUB1, and STAG2 were decreased after WJT treatment, which was identical to the sequencing profiles. CONCLUSIONS: WJT exerted its anti-proliferation and pro-apoptosis effects possibly through suppressing the expression of SMC3, THOC1, BUB1, and STAG2 in RA-FLSs. Thus, therapeutics targeting these genes may be a promising strategy for rescuing RA.

Sequential Infiltration Synthesis of Doped Polymer Films with Tunable Electrical Properties for Efficient Triboelectric Nanogenerator Development.

Doping polymer with AlOx via sequential infiltration synthesis enables bulk modification of triboelectric polymers with tunable electric or dielectric properties, which broadens the material selection and achieves a durable performance gain of triboelectric nanogenerators.

[Sorafenib and octreotide combination therapy can inhibit proliferation of and induce apoptosis in human hepatoma cells].

To investigate the effects of sorafenib and octreotide combination treatment on cellular proliferation and explore the underlying molecular mechanisms by using an in vitro cell culture system with the human hepatoma cell line, HepG2. HepG2 cells were treated with different concentrations of sorafenib and octreotide alone or in combination. Untreated HepG2 cells were used as controls. Treatment-induced cytotoxicity was determined with the cell counting kit-8 by Sigma-Aldrich, and rate of apoptosis was detected by flow cytometry. Fluorescent microscopy was used to observe rates of cell growth under the various treatments. Treatment-induced changes in protein expressions were detected by enzyme-linked immunosorbent assay (for vascular endothelial growth factor (VEGF)) and Western blotting (for the Mcl-1 apoptosis mediator and the ERK1/2 and PERK1/2 kinases). Sorafenib and octreotide, used alone or in combination, inhibited proliferation and induced apoptosis in HepG2 cells. Combination treatment was more effective than either mono-treatment (F = 200.398, P less than 0.05). Fluorescent microscopy showed that combination treatment stimulated phosphatidylserine, the marker of early apoptosis, better than either mono-treatment. VEGF expression in cultures exposed to combination treatment was also significantly lower than in mono-treatment or untreated control cultures (F = 1019.725, P less than 0.05). Western blotting showed that octreotide mono-treatment had no effect on Mcl-1 expression (vs. control group; P more than 0.05) and that combination treatment significantly lowered Mcl-1 expression (vs. mono-treatment and control groups; P less than 0.05). None of the treatments affected ERK1/2 expression (all, P more than 0.05), while all treatments significantly lowered PERK1/2 expression (vs. control group; F = 2.401, P less than 0.05) and the combination treatment lowered PERK1/2 significantly more than either mono-treatment (P less than 0.05). Sorafenib and octreotide can inhibit proliferation and induce apoptosis in the human hepatoma cell line, HepG2. Combination treatment is significantly more efficacious (P less than 0.05) and produced synergistic effects. The mechanism underlying this phenomenon may depend on synergistic inhibition of VEGF, the anti-apoptotic protein Mcl-1, and the proliferation-inducing PERK1/2.

Foxl1 is a marker of bipotential hepatic progenitor cells in mice.

UNLABELLED: The liver contains a population of small bipotential facultative progenitor cells that reconstitute liver function when mature hepatocytes or cholangiocytes are unable to proliferate. Mesenchymal markers, including members of the forkhead transcription factor gene family, have been detected in hepatic progenitor cells. The winged helix transcription factor Foxl1 localizes to mesenchymal cells in the intestine; however, its expression in the liver has not been reported. We found that Foxl1 is expressed in rare cells in the normal liver but is dramatically induced in the livers of mice that have undergone bile duct ligation or were fed a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-containing or choline-deficient, ethionine-supplemented diet. In addition, we employed genetic lineage tracing using a Foxl1-Cre transgenic mouse crossed with the Rosa26R lacZ reporter line to demonstrate that Foxl1-Cre-expressing cells are present within the periportal region shortly after injury. These cells give rise to both hepatocytes [marked by hepatocyte nuclear factor 4 alpha (HNF-4alpha) expression] and cholangiocytes (marked by CK19 expression), indicating that these cells are derived from Foxl1-Cre-expressing cells. Foxl1-Cre-expressing cells are distinct from hepatic stellate cells, portal fibroblasts, and myofibroblasts, although they are located in close proximity to portal fibroblasts. These results demonstrate that the early Foxl1-Cre lineage cell gives rise to both cholangiocytes and hepatocytes after liver injury and suggest the potential for progenitor-portal fibroblast cell interactions. CONCLUSION: We propose that Foxl1 is a bona fide marker of the facultative progenitor cell in the mouse liver.

Antinecrotic and antiapoptotic effects of hepatocyte growth factor on cholestatic hepatitis in a mouse model of bile-obstructive diseases.

Cholestasis, an impairment of bile outflux, frequently occurs in liver diseases. In this process, an overaccumulation of bile acids causes hepatocyte necrosis and apoptosis, leading to advanced hepatitis. Hepatocyte growth factor (HGF) is mitogenic toward hepatocytes, but it is still unclear whether HGF has physiological and therapeutic functions during the progression of cholestasis. Using anti-HGF IgG or recombinant HGF in mice that had undergone bile duct ligation (BDL), we investigated the involvement of HGF in cholestasis-induced hepatitis. After the BDL surgery, HGF and c-Met mRNA levels transiently increased in livers during the progression of cholestatic hepatitis. When c-Met tyrosine phosphorylation was blocked in the livers of BDL-treated mice by anti-HGF IgG, hepatic dysfunction became evident, associated with the acceleration of hepatocyte necrosis and apoptosis. Inversely, administration of recombinant HGF into the mice led to the prevention of cholestasis-induced inflammation: HGF suppressed the hepatic expression of intracellular adhesion molecule-1 and neutrophil infiltration in BDL-treated mice. As a result, parenchymal necrosis was suppressed in the HGF-injected BDL mice. In addition, HGF supplement therapy reduced the number of apoptotic hepatocytes in cholestatic mice, associated with the early induction of Bcl-xL. The administration of HGF enhanced hepatic repair, via accelerating G1/S progression in hepatocytes. Our study showed that 1) upregulation of HGF production is required for protective mechanisms against cholestatic hepatitis and 2) enhancement of the intrinsic defense system by adding HGF may be a reasonable strategy to attenuate hepatic inflammation, necrosis, and apoptosis under bile-congestive conditions.