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IL-22 induces IL-18 expression by intestinal epithelial cells. Authors show here that IL-18 is a key barrier maintenance factor during adherent-invasive E. coli invasion, inducing expression of anti-microbial genes in Paneth cells via Stat3, prompting IFNγ expression in T cells and triggering intestinal Lgr5+ stem cell expansion via Tcf4.

Galectins are carbohydrate binding proteins previously implicated in sensing and repairing damaged lysosomes. Here, the authors show that galectin-9 has specific lysosomal roles in autophagy and contributes to cell degeneration and apoptosis in colitis and pancreatitis in mice.

Red yeast rice (RYR) is known for its lipid-lowering effects in patients with hypercholesterolemia; however, its comparative efficacy with statins and risk reduction remains uncertain. This retrospective study analyzed data from 337,104 patients with hyperlipidemia in the Chang Gung Research Database cohort, spanning from January 2016 to December 2021. Exclusion criteria were applied to ensure data completeness and compliance, including an age limit of < 1 8 years, absence of RYR or statin treatment, and a treatment duration of < 3 0 days. Propensity score matching was employed to minimize bias based on baseline factors, with one patient matching with four patients in the comparison group. The study encompassed a total of 5,984 adult hyperlipidemic patients, with 1,197 in the RYR group and 4,787 in the statin group. The patients were also stratified into statin (n = 8 8 0) or combined use (n = 2 2 0) groups for further comparison. Following one year of treatment, both the RYR and statin groups exhibited reductions in total cholesterol and triglyceride levels. Most biochemical parameters showed no significant differences, except for elevated glutamic oxaloacetic transaminase levels in the RYR group (p = 0. 0 2 6) and increased glycohemoglobin levels in the statin group at the three-month mark (p = 0. 0 3 5). In patients with comorbid diabetes, hypertension, kidney, or liver diseases, RYR and statins demonstrated comparable risks for emergency room (ER) visits, stroke, and myocardial infarction (MI). However, the combination of RYR and statins was associated with reduced stroke-related hospitalizations in patients with diabetes, hypertension, and kidney disease, as well as decreased MI-related hospitalizations in patients with hypertension and kidney disease (all p < 0. 0 0 0 1). In conclusion, both RYR and statins effectively lower blood lipid levels and mitigate related complications. Combining these therapies may lead to fewer ER visits, reduced stroke frequency, and fewer MI hospitalizations in hypertensive and kidney disease patients, and they decreased all-cause mortality in the kidney disease population. Further research on combined therapy is warranted. [ABSTRACT FROM AUTHOR]

This study intends to assess the analgesic effects, physical facilitation, and safety of willow bark use in patients with arthritis. Our study was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. PubMed, Scopus, EMBASE, Web of Science, Cochrane, and ClinicalTrials.gov were searched for relative randomized controlled trials (RCTs) describing the efficacy or adverse events of willow bark in patients with arthritis until 12 April 2023. We used Cochrane ROB 2.0 and the Grading of Recommendations, Assessment, Development, and Evaluations system to evaluate the quality of studies and evidence. The meta-analysis was carried out by the fix-effects model. This study included five studies with six RCTs consisting of 329 patients with arthritis. The results showed significant differences in pain relief and improvement in physical status for patients with arthritis between willow bark treatment and placebo groups, and no significant differences in the risk of all adverse events in patients with arthritis between willow bark treatment and placebo. Owing to the potential bias, the certainty and evidence of our findings are still inadequate. Therefore, further RCTs are needed to confirm our results. [ABSTRACT FROM AUTHOR]

In gut epithelium, IL-22 transmits signals through STAT3 phosphorylation (pSTAT3) which provides intestinal immunity. Many components in the IL-22-pSTAT3 pathway have been identified as risk factors for inflammatory bowel disease (IBD) and some of them are considered as promising therapeutic targets. However, new perspectives are still needed to understand IL-22-pSTAT3 signaling for effective clinical interventions in IBD patients. Here, we revealed activating transcription factor 3 (ATF3), recently identified to be upregulated in patients with active IBD, as a crucial player in the epithelial IL-22-pSTAT3 signaling cascade. We found ATF3 is central to intestinal homeostasis and provides protection during colitis. Loss of ATF3 led to decreased crypt numbers, more shortened colon length, impaired ileal fucosylation at the steady state, and lethal disease activity during DSS-induced colitis which can be effectively ameliorated by rectal transplantation of wild-type colonic organoids. Epithelial stem cells and Paneth cells form a niche to orchestrate epithelial regeneration and host-microbe interactions, and IL-22-pSTAT3 signaling is a key guardian for this niche. We found ATF3 is critical for niche maintenance as ATF3 deficiency caused compromised stem cell growth and regeneration, as well as Paneth cell degeneration and loss of anti-microbial peptide (AMP)-producing granules, indicative of malfunction of Paneth/stem cell network. Mechanistically, we found IL-22 upregulates ATF3, which is required to relay IL-22 signaling leading to STAT3 phosphorylation and subsequent AMP induction. Intriguingly, ATF3 itself does not act on STAT3 directly, instead ATF3 regulates pSTAT3 by negatively targeting protein tyrosine phosphatases (PTPs) including SHP2 and PTP-Meg2. Furthermore, we identified ATF3 is also involved in IL-6-mediated STAT3 activation in T cells and loss of ATF3 leads to reduced capacity of Th17 cells to produce their signature cytokine IL-22 and IL-17A. Collectively, our results suggest that via IL-22-pSTAT3 signaling in the epithelium and IL-6-pSTAT3 signaling in Th17 cells, ATF3 mediates a cross-regulation in the barrier to maintain mucosal homeostasis and immunity.

Inhibiting proteasome functional insufficiency plays an essential role in cancer prevention. Alternative strategies to target ubiquitin enzymes and ubiquitin-signal autophagic degradation can be the potential treatments. Phenolic compounds demonstrated anti-cancer effects. Phenolic compounds not only effectively inhibit E1, deubiquitinating enzyme, and 26S activity but also induce apoptosis in A549 cells. The IC50 of 26S activity and LD50 of A549 cells were nearly equivalent. Therefore, apoptosis may occur via the inhibition of the 26S proteasome activity. Inhibition of the proteasome by tannic acid in A549 cells resulted in reduction of S5a and 20S, accumulation of ubiquitin, and degradation of PARP, followed by induction of apoptosis. USP15 may play an essential role in the stability and activity of caspase-3. The levels of S5a, USP15 and USP47 were regulated by phenolic compounds, and the levels of procaspase-3 and polyADP-ribose polymerase were also decreased in A549 cells treated with phenolic compounds. Interestingly, tannic acid decreased Ub-conjugates while M + G + E increased the accumulation of Ub-conjugates in A549 reporter cells, whereas ubiquitin, E1, and USP47 levels were low in M + G + E-treated A549 reporter cells at 24 hours. Taken together, phenolic compounds may play an important role in mediating apoptosis by regulating the ubiquitin–proteasome pathway and autophagy system.

Background. Ischemic heart disease (IHD) related to cardiovascular or cerebrovascular disease is the leading cause of mortality and an important issue of public health worldwide. The cost of long-term healthcare for IHD patients may result in a huge financial burden. Objectives. To analyze the medical expenditure incurred for and survival of IHD patients treated with Chinese herbal medicine (CHM) and Western medicine. Methods. Subjects were randomly selected from the National Health Insurance Research Database in Taiwan. The Cox proportional hazards regression model, Kaplan–Meier estimator, logrank test, chi-square test, and analysis of variance were applied. Landmark analysis was used to assess the cumulative incidence of death in IHD patients. Results. We identified 11,527 users of CHM combined with Western medicine and 11,527 non-CHM users. CHM users incurred a higher medical expenditure for outpatient care within 1 (24,529 NTD versus 18,464 NTD, P value <0.0001) and 5 years (95,345 NTD versus 60,367 NTD, P value <0.0001). However, CHM users had shorter hospitalizations and lower inpatient medical expenditure (7 days/43,394 NTD in 1 year; 11 days/83,141 NTD in 5 years) than non-CHM users (11 days/72,939 NTD in 1 year; 14 days/107,436 NTD in 5 years). The CHM group's adjusted hazard ratio for mortality was 0.41 lower than that of the non-CHM group by Cox proportional hazard models with time-dependent exposure covariates. Danshen, Huang qi, Niu xi, Da huang, and Fu zi were the most commonly prescribed Chinese single herbs; Zhi-Gan-Cao-Tang, Xue-Fu-Zhu-Yu-Tang, Tian-Wang-Bu-Xin-Dan, Sheng-Mai-San, and Yang-Xin-Tang were the five most frequently prescribed herbal formulas in Taiwan. Conclusions. Combining Chinese and Western medicine can reduce hospital expenditure and improve survival for IHD patients. [ABSTRACT FROM AUTHOR]

Background: Spinal cord injury (SCI) often involves multimodal pain control. This study aims to evaluate the efficacy and safety of cannabinoid use for the reduction of pain in SCI patients. Methods and Findings: This study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. We searched PubMed, EMBASE, Scopus, Cochrane, Web of Science, and ClinicalTrials.gov for relevant randomized controlled trials (RCTs) reporting the efficacy (e.g., pain relief) or safety (e.g., adverse events) of cannabinoids in patients with SCI, from inception to 25 December 2021. The study quality and the quality of evidence were evaluated by Cochrane ROB 2.0 and the Grading of Recommendations, Assessment, Development, and Evaluations system (GRADE), respectively. We used the random-effects model to perform the meta-analysis. From a total of 9,500 records, we included five RCTs with 417 SCI patients in the systematic review and meta-analysis. We judged all five of the included RCTs as being at high risk of bias. This meta-analysis indicated no significant difference in pain relief between the cannabinoids and placebo in SCI patients (mean difference of mean differences of pain scores: −5.68; 95% CI: −13.09, 1.73; p = 0.13; quality of evidence: very low), but higher odds of adverse events were found in SCI patients receiving cannabinoids (odds ratio: 3.76; 95% CI: 1.98, 7.13; p < 0.0001; quality of evidence: moderate). Conclusion: The current best evidence suggests that cannabinoids may not be beneficial for pain relief in SCI patients, but they do increase the risks of adverse events, including dizziness, somnolence, and dysgeusia, compared to the placebo. Cannabinoids should not be regularly suggested for pain reduction in SCI patients. Updating the systematic reviews and meta-analyses by integrating future RCTs is necessary to confirm these findings. [ABSTRACT FROM AUTHOR]

Background. Traditional Chinese Medicine (TCM) relieves associated symptoms of hyperthyroidism such as heat intolerance, palpitations, tremor, anxiety, weight loss, increased frequency of bowel movements, and shortness of breath. However, there are no studies regarding the core prescription patterns of herbal formula and single herbs for hyperthyroidism in Taiwan. Materials and Methods. This is a retrospective, observational study using the National Health Insurance Research Database (NHIRD) in Taiwan to analyze the prescription patterns of TCM. Demographic factors, such as sex, age, occupational status, and residential area, and the risk factors for hyperthyroidism were also studied. Results. The outpatient or/and inpatient services for hyperthyroidism receive 17,707 cases in a year. Overall, there were 13,394 newly diagnosed patients. TCM was used in 73% of the patients, and 77.3% of the patients were females. The acceptability of TCM was higher among female patients. Most patients were diagnosed with hyperthyroidism between the ages of 30 and 49 years. The most common comorbidity identified was diabetes mellitus. The most commonly prescribed Chinese herbal product (CHP) formula was Jia-Wei-Xia-Yao-San, while Xia-Ku-Cao was the most commonly prescribed single CHP. There was a high coprescription rate for Xuan-Shen, Bei-Mu, and Mu-Li. Conclusion. This study describes the core prescription pattern of TCM used in the treatment of patients with hyperthyroidism in Taiwan. The most frequently used CHPs could be potential candidates for future pharmacologic studies or clinical trials. [ABSTRACT FROM AUTHOR]

Objective: While radix Salvia miltiorrhiza (Danshen; RSM) is commonly used in Chinese herbal medicine, its current usage has not yet been analyzed in a large-scale survey. This study aimed to investigate the conditions for which RSM is prescribed and the utilization of RSM in Taiwan. Methods: 1 million beneficiaries enrolled in the Taiwan National Health Insurance Research Database were sampled to identify patients who were prescribed RSM. Next, the diagnoses of these patients based on the International Classification of Diseases 9th Revision Clinical Modification code were analyzed. Logistic regression analysis was employed to estimate the odds ratio (OR) for RSM utilization. Results: Patients with disorders of menstruation and abnormal bleeding from the female genital tract due to other causes were the diagnostic group most commonly treated with RSM (9.48%), followed by those with general (9.46%) and cardiovascular symptoms (4.18%). Subjects treated with RSM were mostly aged 35–49 years (30.1%). The most common combination of diseases for which RSM was prescribed (0.17%) included menopausal disorders and general symptoms. Women were more likely to receive RSM than men (OR = 1.75, 95% confidence interval = 1.73–1.78). RSM was frequently combined with Yan-Hu-Suo and Jia-Wei-Xiao-Yao-San for clinical use. Conclusion: To date, this is the first study to identify the most common conditions for which RSM is used in modern Taiwan. The results indicate RSM as a key medicinal herb for the treatment of gynecological diseases, including menstrual disorders, female genital pain, menopausal disorders, etc. The most common combination for which RSM is prescribed is menopausal disorders and general symptoms. Further research is needed to elucidate the optimal dosage, efficacy, and safety of RSM. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the efficacy of laser acupuncture (LA) therapy in patients with dry eye disease (DED). Design: A two-center randomized controlled trial. Settings/Location: The Department of Ophthalmology, Chinese Medicine at the Kaohsiung Chang Gung Memorial Hospital, and the Sunming Eye Clinic in South Taiwan. Subjects: Fifty-nine participants ages 20 to 65 years were enrolled and randomly assigned to the experimental group (LA plus conventional treatment) or the sham control group (LA without laser output plus conventional treatment). Interventions: Subjects underwent LA treatment three times a week for 12 weeks. The subjects in the experimental group sequentially received 0.375 J of energy at each of the following acupoints: BL2, TE23, ST2, LI4, ST36, and GB37. Subjects in the control group received a sham LA treatment, without any laser output. Outcome Measures: The primary outcome measure was ocular surface disease index (OSDI). The secondary outcome measures included tear film breakup time (TFBUT), Schirmer-I test finding, and visual analog scale (VAS) score. Results: At 4 and 12 weeks after the first visit, the experimental group showed significant improvement of dry eye symptoms as measured by OSDI, TFBUT, Shirmer-I test, and VAS. Compared with the control group, the OSDI (7.23, p = 0.001) and TFBUT (−1.78, p = 0.001) significantly improved in the experimental group at 12 weeks of treatment. Conclusions: LA improved the symptoms and tear stability related to DED in conjunction with conventional treatment. The authors suggest that LA be considered a complementary therapy for DED when conventional treatment does not provide satisfactory effects. Trial Registration: ClinicalTrials.gov Identifier NCT03204903. [ABSTRACT FROM AUTHOR]

Bone mineral density (BMD) has been validated not only for the diagnosis of osteoporosis but also for prediction of the risk of osteoporosis-related fractures. The purpose of this paper was to investigate the overall benefits of herbal medicines on BMD using a meta-analytic method. Systematic searches in PubMed, Medline, Cochrane Central, and China National Knowledge Infrastructure were performed for eligible studies. A meta-analysis was conducted to evaluate the benefits of herbal medicine treatment and conventional treatment for BMD. Herbal medicines frequently used for interventions were pooled in the analysis and further investigated. Seventeen studies were pooled in the meta-analysis and showed that BMD was higher in the herbal medicine group than in the control group (standardized mean difference [SMD]: 0.857; 95% confidence interval [CI]: 0.412 to 1.301). Significant benefits of herbal medicine for BMD were found in the lumbar spine, femoral neck, and femoral trochanter and in postmenopausal women (SMD: 0.600, 95% CI: 0.068 to 1.131) by subgroup analysis. Moreover, through the meta-regression analysis, the age at menopause and the menopause duration were found to influence the herbal intervention effects on BMD. In addition, the most prescribed medicine among the effective herbs in the pooled studies was found to be Epimedium brevicornum Maxim. This paper provides evidence that herbal medicine interventions increase BMD more than conventional treatments in individuals with osteoporosis, especially postmenopausal women. The results of this study suggest that herbal medicines are effective for increasing BMD in individuals with osteoporosis. [ABSTRACT FROM AUTHOR]

Dengue fever is an important epidemic disease with a high prevalence in tropical and subtropical countries. We aimed to investigate the effects of a treatment integrating traditional Chinese (TCM) and Western medicines on dengue inpatients with warning signs (i.e., group B) according to the World Health Organization dengue classification in this retrospective cohort study of medical records. Inpatients who were treated with conventional Western therapies in the absence or presence of TCM were assigned to the control and treatment groups, respectively. Data were compared using an analysis of variance, general linear analysis, and chi-square test. The most common clinical symptoms and signs of dengue fever were fever and muscle ache. The treatment group patients were significantly more likely to present general weakness and poor appetite than the control group patients. Patients in the treatment group were more likely to experience stomachache than those in the control group. Moreover, comparisons of the changes in hemoglobin and alanine aminotransferase levels over time revealed significant differences between the patient groups. Zhu Ye Shi Gao Tang, Gui Pi Tang, Paeonia suffruticosa, and Clerodendrum cyrtophyllum were the most commonly administered TCM formula and single herbs in this study. Patients in the treatment group experienced a resolution of symptoms, signs, and laboratory data and were discharged smoothly, without deterioration to death or critical care. Our findings suggest that the integration of TCM and Western medicine may yield an appropriate treatment for dengue fever. [ABSTRACT FROM AUTHOR]