Puerarin Modulates Hepatic Farnesoid X Receptor and Gut Microbiota in High-Fat Diet-Induced Obese Mice.

Obesity is associated with alterations in lipid metabolism and gut microbiota dysbiosis. This study investigated the effects of puerarin, a bioactive isoflavone, on lipid metabolism disorders and gut microbiota in high-fat diet (HFD)-induced obese mice. Supplementation with puerarin reduced plasma alanine aminotransferase, liver triglyceride, liver free fatty acid (FFA), and improved gut microbiota dysbiosis in obese mice. Puerarin's beneficial metabolic effects were attenuated when farnesoid X receptor (FXR) was antagonized, suggesting FXR-mediated mechanisms. In hepatocytes, puerarin ameliorated high FFA-induced sterol regulatory element-binding protein (SREBP) 1 signaling, inflammation, and mitochondrial dysfunction in an FXR-dependent manner. In obese mice, puerarin reduced liver damage, regulated hepatic lipogenesis, decreased inflammation, improved mitochondrial function, and modulated mitophagy and ubiquitin-proteasome pathways, but was less effective in FXR knockout mice. Puerarin upregulated hepatic expression of FXR, bile salt export pump (BSEP), and downregulated cytochrome P450 7A1 (CYP7A1) and sodium taurocholate transporter (NTCP), indicating modulation of bile acid synthesis and transport. Puerarin also restored gut microbial diversity, the Firmicutes/Bacteroidetes ratio, and the abundance of Clostridium celatum and Akkermansia muciniphila. This study demonstrates that puerarin effectively ameliorates metabolic disturbances and gut microbiota dysbiosis in obese mice, predominantly through FXR-dependent pathways. These findings underscore puerarin's potential as a therapeutic agent for managing obesity and enhancing gut health, highlighting its dual role in improving metabolic functions and modulating microbial communities.

Acupuncture May Help to Prevent Chemotherapy-Induced Peripheral Neuropathy: A Randomized, Sham-Controlled, Single-Blind Study.

OBJECTIVE: This study investigated the efficacy of acupuncture in preventing chemotherapy-induced peripheral neuropathy (CIPN) in patients with colorectal cancer (CRC). METHODS: This single center, randomized, controlled, single-blind clinical trial randomly assigned patients with stage 3 CRC attending outpatient clinics in China Medical University Hospital to either verum or sham acupuncture treatment concurrently with chemotherapy. Primary outcomes were nerve conduction velocity (NCV) and touch thresholds of limb terminals. Secondary outcomes were total and subdomain scores on the Functional Assessment of Cancer Therapy-General (FACT-G), and scores on the FACT/GOG-Ntx subscale and the Brief Pain Inventory-Short Form (BPI-SF), at baseline, weeks 12, 36, and follow-up (week 48). RESULTS: Thirty-two patients met the inclusion criteria and received verum acupuncture (N = 16) or sham acupuncture (N = 16). Under the -intent-to-treat principle, 26 participants were analyzed. Significant changes from baseline for questionnaire scores and sensory NCV were observed in both study groups. Sham acupuncture was associated with significant reductions from baseline in motor NCV and sensory touch thresholds; no such changes were observed with verum acupuncture. No serious adverse events were reported. CONCLUSION: Prophylactic acupuncture may exert neuroprotective effects on mechanical or tactile touch thresholds during chemotherapy regimens in patients with CRC, with evidence of this protectiveness persisting at 6 months' follow-up. The lack of change in motor NCV values with verum acupuncture indicates neuroprotective effects. Sensory NCV values and patient-reported outcomes did not differ significantly between the study groups.

Farnesoid X Receptor Agonist GW4064 Protects Lipopolysaccharide-Induced Intestinal Epithelial Barrier Function and Colorectal Tumorigenesis Signaling through the αKlotho/ßKlotho/FGFs Pathways in Mice.

The farnesoid X receptor (FXR)/ßKlotho/fibroblast growth factors (FGFs) pathway is crucial for maintaining the intestinal barrier and preventing colorectal cancer (CRC). We used an FXR agonist, GW4064, and FXR-knockout (FXR-KO) mice to investigate the role of FXR/Klothos/FGFs pathways in lipopolysaccharide (LPS)-induced intestinal barrier dysfunction and colon carcinogenesis. The results showed that upregulation of FXR in enterocytes effectively ameliorated intestinal tight-junction markers (claudin1 and zonula occludens-1), inflammation, and bile acid levels, thereby protecting mice from intestinal barrier dysfunction and colon carcinogenesis. GW4064 treatment increased FXR, αKlotho, ßKlotho, FGF19, FGF21, and FGF23 in wild-type mice exposed to LPS, while FXR-KO mice had decreased levels. FXR-KO mice exhibited elevated colon cancer markers (ß-catenin, LGR5, CD44, CD34, and cyclin D1) under LPS, underscoring the pivotal role of FXR in inhibiting the development of colon tumorigenesis. The varying gut microbiota responses in FXR-KO mice versus wild-type mice post LPS exposure emphasize the pivotal role of FXR in preserving intestinal microbial health, involving Bacteroides thetaiotaomicron, Bacteroides acidifaciens, and Helicobacter hepaticus. Our study validates the effectiveness of GW4064 in alleviating LPS-induced disruptions to the intestinal barrier and colon carcinogenesis, emphasizing the importance of the FXR/αKlotho/ßKlotho/FGFs pathway and the interplay between bile acids and gut microbiota.

Kawasaki disease in childhood and psychiatric disorders: A population-based case-control prospective study in Taiwan.

BACKGROUND: Kawasaki disease (KD) is a common childhood acute inflammatory disease and potentially triggers a chronic inflammation. Although some researches have investigated neurodevelopmental consequences following KD, the findings have been inconsistent. This is the first population-based study targeted on KD and common psychiatric disorders. OBJECTIVES: We aimed to investigate the association between KD and psychiatric disorders and hypothesized that standard anti-inflammatory treatment by intravenous immunoglobulin (IVIG) may protect against development of psychiatric disorders. METHOD: We retrieved data from Taiwan's National Health Insurance Research database (NHIRD). Patients (n = 282,513) with psychiatric disorders (the case group) during 1997-2013 were included, and the control group was matched with age, sex, income and urbanization (1:1). We calculated the prevalence of KD in both groups and estimated odd ratios (ORs) and 95% confidence intervals (CIs) in the subgroup analyses for KD in conditions of age, severity, and common psychiatric comorbidity. RESULTS: Numbers of patients with KD were 460 in the cases and 380 in the controls (p = .006), and the crude OR of KD was 1.21 times greater (95% CI = 1.06-1.39, p = .006) in the case than the control groups. KD patients without IVIG treatment (n = 126) were higher in the cases than those in the controls (n = 54), with the OR of 2.33 (95% CI = 1.70-3.21, p < .0001). Subgroup analyses showed that KD survivors were at significant risk for autism spectrum disorders (ASD) (OR = 2.15, 95% CI = 1.27-3.65; p = .005) and attention deficit and hyperactivity disorders (ADHD) (OR = 1.19, 95% CI = 1.02-1.39; p = 0.03), and a trend of increased risk for anxiety disorders (OR = 1.36, 95%CI = 0.99-1.86; p = 0.05). CONCLUSIONS: Patients with KD were more likely to have comorbid psychiatric disorders, including ASD and ADHD. Moreover, anti-inflammatory treatment with IVIG may have potential prophylactic effects against the development of psychiatric disorders.

Predicting frailty in older adults using vocal biomarkers: a cross-sectional study.

BACKGROUND: Frailty is a common issue in the aging population. Given that frailty syndrome is little discussed in the literature on the aging voice, the current study aims to examine the relationship between frailty and vocal biomarkers in older people. METHODS: Participants aged ≥ 60 years visiting geriatric outpatient clinics were recruited. They underwent frailty assessment (Cardiovascular Health Study [CHS] index; Study of Osteoporotic Fractures [SOF] index; and Fatigue, Resistance, Ambulation, Illness, and Loss of weight [FRAIL] index) and were asked to pronounce a sustained vowel /a/ for approximately 1 s. Four voice parameters were assessed: average number of zero crossings (A1), variations in local peaks and valleys (A2), variations in first and second formant frequencies (A3), and spectral energy ratio (A4). RESULTS: Among 277 older adults, increased A1 was associated with a lower likelihood of frailty as defined by SOF (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.74-0.96). Participants with larger A2 values were more likely to be frail, as defined by FRAIL and CHS (FRAIL: OR 1.41, 95% CI 1.12-1.79; CHS: OR 1.38, 95% CI 1.10-1.75). Sex differences were observed across the three frailty indices. In male participants, an increase in A3 by 10 points increased the odds of frailty by almost 7% (SOF: OR 1.07, 95% CI 1.02-1.12), 6% (FRAIL: OR 1.06, 95% CI 1.02-1.11), or 6% (CHS: OR 1.06, 95% CI 1.01-1.11). In female participants, an increase in A4 by 0.1 conferred a significant 2.8-fold (SOF: OR 2.81, 95% CI 1.71-4.62), 2.3-fold (FRAIL: OR 2.31, 95% CI 1.45-3.68), or 2.8-fold (CHS: OR 2.82, 95% CI 1.76-4.51, CHS) increased odds of frailty. CONCLUSIONS: Vocal biomarkers, especially spectral-domain voice parameters, might have potential for estimating frailty, as a non-invasive, instantaneous, objective, and cost-effective estimation tool, and demonstrating sex differences for individualised treatment of frailty.

Chinese herbal medicine SS-1 inhibits T cell activation and abrogates TH responses in Sjögren's syndrome.

BACKGROUND/PURPOSE: Sjögren's syndrome (SS) is an autoimmune disease and its conventional treatment has exhibited limited therapeutic efficacy. Traditional Chinese medicine has been demonstrated to ameliorate the sicca symptoms of SS by decreasing the level of TH1 and TH2 cytokines and increasing salivary flow rate. A newly designed traditional Chinese medicine, SS-1, showed improved efficacy in alleviating the dryness symptoms of SS patients in the National Taiwan SS cohort investigation. Here, we investigated the effect of SS-1 on T cell responses. METHODS: SS-1 was authenticated and its major compounds were verified by high-performance liquid chromatography. We examined the effects of SS-1 on the activation and TH1, TH2, and TH17 polarization of murine T cells. We also determined the level of TH1, TH2, and TH17 cytokine RNA in peripheral blood mononuclear cells of SS patients before and after SS-1 treatment. RESULTS: SS-1 treatment inhibits the activation and TH1, TH2, and IL-17A+IFNγ+ TH polarization of murine T cells. SS-1 treatment also significantly reduces IFN-γ, IL-4, and IL-13 expression, and moderately reduces IL-17A expression in peripheral blood mononuclear cells of SS patients. CONCLUSION: Our results suggest that SS-1 inhibits T cell activation and diminishes TH1, TH2, and IL-17+IFN-γ+ TH responses in SS patients.

Efficacy of Electronic Acupuncture Shoes for Chronic Low Back Pain: Double-Blinded Randomized Controlled Trial.

BACKGROUND: Chronic low back pain is a common problem and is associated with high costs, including those related to health care and indirect costs due to absence at work or reduced productivity. Previous studies have demonstrated that acupuncture or electroacupuncture can relieve low back pain. Electronic acupuncture shoes (EAS) are a novel device designed in this study. This device combines the properties of acupuncture and transcutaneous electrical nerve stimulation for clinical use. OBJECTIVE: The aim of this study was to evaluate the efficacy of EAS in patients with chronic low back pain. METHODS: In this prospective double-blinded randomized controlled study, the data of 83 patients who experienced chronic low back pain were analyzed. Patients came to our clinic for 20 visits and underwent assessment and treatment. Patients were randomly allocated to receive either EAS plus placebo nonsteroidal anti-inflammatory drugs (NSAIDs) (EAS group, n=42) or sham EAS plus NSAIDs (NSAID group, n=41). The visual analog scale (VAS) score and range of motion were assessed at baseline, before and after each EAS treatment, and 2 weeks after the last treatment. The time for achieving pain remission was recorded. Quality of life was assessed at the 2nd, 14th, and 20th visits. RESULTS: After 6 weeks of treatment, the treatment success rate in each visit in the EAS group was higher than that in the NSAID group, as revealed by the intention-to-treat (ITT) and per-protocol (PP) analyses, but significant differences were observed only during the 16th visit in the ITT analysis (EAS group: 31/37, 84% and NSAID group: 21/34, 62%; P=.04). The change in the VAS score from baseline in each visit in the EAS group was greater than that in the NSAID group, as revealed by the ITT and PP analyses, and significant differences were observed in the 5th visit and 9th visit in the ITT analysis (P=.048 and P=.048, respectively). Significant differences were observed in the left rotation in the 2nd visit and 4th visit (P=.049 and P=.03, respectively). No significant differences were observed in the VAS score before and after treatment in each visit and in the quality of life in both groups. CONCLUSIONS: EAS might serve as a reliable alternative therapeutic tool for patients with chronic low back pain who are contraindicated for oral NSAIDs. TRIAL REGISTRATION: ClinicalTrials.gov NCT02468297 https://clinicaltrials.gov/ct2/show/NCT02468297.

Acupuncture Therapy and Incidence of Depression After Stroke.

BACKGROUND AND PURPOSE: We investigated whether use of acupuncture within a 3-month poststroke period after hospital discharge is associated with reduced risk of depression. METHODS: This cohort study included 16 046 patients aged ≥18 years with an initial hospitalization for stroke during 2000 and 2012 in the claims database of a universal health insurance program. Patients who had received acupuncture therapies within 3 months of discharge were defined as acupuncture users (n=1714). All patients were followed up for incidence of depression until the end of 2013. We assessed the association between use of acupuncture and incidence of depression using Cox proportional hazards models in all subjects and in propensity score-matched samples consisting of 1714 pairs of users and nonusers. RESULTS: During the follow-up period, the incidence of depression per 1000 person-years was 11.1 and 9.7 in users and nonusers, respectively. Neither multivariable-adjusted Cox models (hazard ratio, 1.04; 95% confidence interval, 0.84-1.29) nor the propensity score-matching model (hazard ratio, 1.06; 95% confidence interval, 0.79-1.42) revealed an association between use of acupuncture and incidence of depression. CONCLUSIONS: In patients admitted to hospital for stroke, acupuncture therapy within 3 months after discharge was not associated with subsequent incidence of depression.

Transformation of 5-D itch scale and numerical rating scale in chronic hemodialysis patients.

BACKGROUND: Pruritus is a common and frustrating symptom in hemodialysis (HD) patients and 5-D itch scale is proposed as a reliable measurement of pruritus. However, information regarding 5-D itch scale categories is currently unavailable. We explored optimal cut-offs 5-D itching scale based on numerical rating scale (NRS) categories in HD patients. METHODS: Four hundred and nine HD patients in China Medical University Hospital in December 2014 were included and severity of pruritus was estimated using NRS and 5-D itch scale. The association of NRS and 5-D itch scale was analyzed by linear regression. The optimal cut-offs for 5-D itch scale based on NRS categories were generated. RESULTS: The average NRS was 3.4 ± 3.0 and the average 5-D itch scale was 10.9 ± 4.8. The 5-D score was strongly correlated with the NRS: r = 0.831 (p < 0.001). NRS = -2.31 + 0.52 × (5-D scale). The averages of 5-D scales were 6.4 ± 1.5, 9.6 ± 2.2, 13.1 ± 3.2, 15.7 ± 4.4, 19.5 ± 4.4 for no, mild, moderate, severe, and very severe pruritus based on categorized NRS. A 5-D itch scale categories were proposed, ≤ 8 for NRS = 0, 9-11 for mild pruritus, 12-17 for moderate pruritus, 18-21 for severe pruritus and ≥ 22 for very severe pruritus. CONCLUSIONS: Categories for the 5-D itch scale were proposed based on the measurements of pruritus severity in HD patients. This information provides a simple solution that enables transformation between the 5-D itch scale and the numerical rating scale.

Alpinia oxyphylla Miq. fruit extract activates IGFR-PI3K/Akt signaling to induce Schwann cell proliferation and sciatic nerve regeneration.

BACKGROUND: It is known that the medicinal herb Alpinia oxyphylla Miq. is widely used as a remedy for diarrhea as well as the symptoms accompanying hypertension and cerebrovascular disorders. Moreover, it has also been reported that Alpinia oxyphylla Miq. has beneficial effects on anti-senescence and neuro-protection. This study focuses on the molecular mechanisms by which the Alpinia oxyphylla Miq. fruits promote neuron regeneration. METHODS: A piece of silicone rubber was guided across a 15 mm gap in the sciatic nerve of a rat. This nerve gap was then filled with various doses of Alpinia oxyphylla Miq. fruits to assess their regenerative effect on damaged nerves. Further, we investigated the role of Alpinia oxyphylla Miq. fruits in RSC96 Schwann cell proliferation. RESULTS: Our current results showed that treatment with the extract of Alpinia oxyphylla Miq. fruits triggers the phosphorylated insulin-like growth factor-1 receptor- phosphatidylinositol 3-kinase/serine-threonine kinase pathway, and up-regulated the proliferating cell nuclear antigen in a dose-dependent manner. Cell cycle analysis on RSC96 Schwann cells showed that, after exposure to Alpinia oxyphylla Miq. fruit extract, the transition from the first gap phase to the synthesis phase occurs in 12-18 h. The expression of the cell cycle regulatory proteins cyclin D1, cyclin E and cyclin A increased in a dose-dependent manner. Transfection with a small interfering RNA blocked the expression of phosphatidylinositol 3-kinase and induced down-regulation both on the mRNA and protein levels, which resulted in a reduction of the expression of the survival factor B-cell lymphoma 2. CONCLUSION: We provide positive results that demonstrate that Alpinia oxyphylla Miq. fruits facilitate the survival and proliferation of RSC96 cells via insulin-like growth factor-1 signaling.

Treatment of allergic rhinitis with acupoint herbal plaster: an oligonucleotide chip analysis.

BACKGROUND: Allergic rhinitis is regarded as an imbalanced Th1/Th2 cell-mediated response. The present study used microarray analysis to compare gene expression levels between allergic rhinitis patients before and after a series of acupoint herbal plaster applications. METHODS: In this experimental pilot study, volunteers experiencing sneezing, runny nose, and congestion for more than 9 months in the year following initial diagnoses were included after diagnostic confirmation by otolaryngologists to exclude patients with sinusitis and nasal polyps. Patients with persistent allergic rhinitis each received four acupoint herbal plaster treatments applied using the moxibustion technique. Clinical outcomes were evaluated using the Rhinitis Quality of Life Questionnaire (RQLQ). Peripheral blood samples were analyzed using an ImmunoCAP Phadiatop test, and patients were classified as phadiatop (Ph)-positive or -negative. Microarray results were analyzed for genes that were differentially expressed between (1) Ph-positive and -negative patients treated with herbal plaster; and (2) before and after herbal plaster treatment in the Ph-positive patient group. Unsupervised and supervised methods were used for gene-expression data analysis. RESULTS: Nineteen Ph-positive and four Ph-negative participants with persistent allergic rhinitis were included in the study. RQLQ results indicated that the 19 Ph-positive volunteers experienced improvement in six of seven categories following acupoint herbal plaster treatments, whereas the four Ph-negative participants reported improvement in only two categories. Hierarchical clustering and principle component analysis of the gene expression profiles of Ph-positive and -negative participants indicated the groups exhibited distinct physiological responses to acupoint herbal treatment. Evaluation of gene networks using MetaCore identified that the "Immune response_IL-13 signaling via JAK-STAT" and the "Inflammation_Interferon signaling" were down- and up-regulated, respectively, among Ph-positive subjects. CONCLUSIONS: In this preliminary study, we find that the IL-13 immune response via JAK-STAT signaling and interferon inflammation signaling were down- and upregulated, respectively, in the Ph-positive group. Further studies are required to verify these pathways in Ph-positive patients, and to determine the mechanism of such pathway dysregulation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02486159 . Registered 30 Jun 2015.

The association between arterial stiffness and tongue manifestations of blood stasis in patients with type 2 diabetes.

BACKGROUND: Diabetes mellitus (DM) is a hypercoagulable state and is associated with highly increased risk of vascular complications. In the theory of traditional Chinese medicine (TCM), these vascular complications are classified as blood stasis. Diagnosis of the tongue plays an important role in TCM; a bluish tongue, petechiae, and engorged sublingual collateral vessels are manifestations of blood stasis. This study aimed to characterize the tongue manifestations of blood stasis and derive a relationship between blood stasis and vascular disorders in patients with type 2 DM. METHOD: We conducted a cross-sectional study of 140 patients with type 2 DM, and compared demography, laboratory, physical examination, ankle brachial index(ABI), brachial-ankle pulse wave velocity (ba-PWV), and tongue manifestation datas. An automatic tongue diagnosis system was used to capture tongue images and characterize clinical tongue manifestations. RESULTS: A bluish or petechiae tongue was assoicated with a significant decrease in high-density lipoprotein level, and bluish tongue was associated with significant increase in blood triglyceride in patients with type 2 DM. On assessing arterial stiffness, patients with a petechiae tongue had a higher ba-PWV for both sides (L:1938.41 ± 469.54 cm/sec v.s.1723.99 ± 302.16, p = 0.02; R:1937.28 ± 405.55 v.s.1741.99 ± 325.82, p = 0.03). CONCLUSION: Blood stasis, particularly a tongue with petechiae, may be associated with arterial stiffness in patients with type 2 DM. Furthermore, tongue diagnosis could detect blood stasis relevant to DM and could serve as a feasible predictor for DM.

Validation of a new simple scale to measure symptoms in heart failure from traditional Chinese medicine view: a cross-sectional questionnaire study.

BACKGROUND: Current clinical practices used to functionally classify heart failure (HF) are time-consuming, expensive, or require complex calculations. This study aimed to design an inquiry list from the perspective of traditional Chinese medicine (TCM) that could be used in routine clinical practice to resolve these problems. METHODS: The severity of documented HF in 115 patients was classified according to their performance in maximal exercise tests into New York Heart Association (NYHA) functional classification (FC) II or NYHA FC III. Concomitantly, the patients were assessed using the new TCM inquiry list and two validated quality of life questionnaires, namely, the Short Form 36 (SF-36) generic scale and the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Factor analysis was applied to extract the core factors from the responses to the items in TCM inquiry list; logistic regression analysis was then used to predict the severity of HF according to the extracted factors. RESULTS: The TCM inquiry list showed moderate levels of correlation with the physical and emotional components of the SF-36 and the MLHFQ, and predicted the functional class of HF patients reliably using logistic regression analysis, with a correct prediction rate with 64.3 %. Factor analysis of the TCM inquiry list extracted five core factors, namely, Qi Depression, Heart Qi Vacuity and Blood Stasis, Heart Blood Vacuity, Dual Qi-Blood Vacuity, and Yang Vacuity, from the list, which aligned with the perspective of TCM as it relates to the pattern of HF. The correct prediction rate rose to 70.4 % when Dual Qi-Blood Vacuity was combined with the MLHFQ. The excessive false-negative rate is a problem associated with the TCM inquiry list. CONCLUSIONS: The TCM inquiry list is a simple scale and similar to patient-reported subjective measures of quality of life in HF, and may help to classify patients into NYHA FC II or NYHA FC III. Factor 4 addresses dizziness, dizzy vision and general weakness, which are critical parameters that distinguish between NYHA FC II and NYHA FC III. Incorporating these three items into the management of HF may help to classify patients from a functional perspective.

Anti-Apoptotic and Pro-Survival Effect of Alpinate Oxyphyllae Fructus (AOF) in a d-Galactose-Induced Aging Heart.

Aging, a natural biological/physiological phenomenon, is accelerated by reactive oxygen species (ROS) accumulation and identified by a progressive decrease in physiological function. Several studies have shown a positive relationship between aging and chronic heart failure (HF). Cardiac apoptosis was found in age-related diseases. We used a traditional Chinese medicine, Alpinate Oxyphyllae Fructus (AOF), to evaluate its effect on cardiac anti-apoptosis and pro-survival. Male eight-week-old Sprague-Dawley (SD) rats were segregated into five groups: normal control group (NC), d-Galactose-Induced aging group (Aging), and AOF of 50 (AL (AOF low)), 100 (AM (AOF medium)), 150 (AH (AOF high)) mg/kg/day. After eight weeks, hearts were measured by an Hematoxylin-Eosin (H&E) stain, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-assays and Western blotting. The experimental results show that the cardiomyocyte apoptotic pathway protein expression increased in the d-Galactose-Induced aging groups, with dose-dependent inhibition in the AOF treatment group (AL, AM, and AH). Moreover, the expression of the pro-survival p-Akt (protein kinase B (Akt)), Bcl-2 (B-cell lymphoma 2), anti-apoptotic protein (Bcl-xL) protein decreased significantly in the d-Galactose-induced aging group, with increased performance in the AOF treatment group with levels of p-IGFIR and p-PI3K (Phosphatidylinositol-3' kinase (PI3K)) to increase by dosage and compensatory performance. On the other hand, the protein of the Sirtuin 1 (SIRT1) pathway expression decreased in the aging groups and showed improvement in the AOF treatment group. Our results suggest that AOF strongly works against ROS-induced aging heart problems.

The Traditional Chinese Medicine DangguiBuxue Tang Sensitizes Colorectal Cancer Cells to Chemoradiotherapy.

Chemotherapy is an important treatment modality for colon cancer, and concurrent chemoradiation therapy (CCRT) is the preferred treatment route for patients with stage II and III rectal cancer. We examined whether DangguiBuxue Tang (DBT), a traditional Chinese herbal extract, sensitizes colorectal cancer cells to anticancer treatments. The polysaccharide-depleted fraction of DBT (DBT-PD) contains greater amounts of astragaloside IV (312.626 µg/g) and ferulic acid (1.404 µg/g) than does the original formula. Treatment of the murine colon carcinoma cell line (CT26) with DBT-PD inhibits growth, whereas treatment with comparable amounts of purified astragaloside IV and ferulic acid showed no significant effect. Concurrent treatment with DBT-PD increases the growth inhibitory effect of 5-fluorouracil up to 4.39-fold. DBT-PD enhances the effect of radiation therapy (RT) with a sensitizer enhancement ratio (SER) of up to 1.3. It also increases the therapeutic effect of CCRT on CT26 cells. Cells treated with DBP-PD showed ultrastructural changes characteristic of autophagy, including multiple cytoplasmic vacuoles with double-layered membranes, vacuoles containing remnants of degraded organelles, marked swelling and vacuolization of mitochondria, and autolysosome-like vacuoles. We conclude that DBT-PD induces autophagy-associated cell death in CT26 cells, and may have potential as a chemotherapy or radiotherapy sensitizer in colorectal cancer treatment.

Central and Peripheral Hemodynamic Adaptations During Cardiopulmonary Exercise Test in Heart Failure Patients With Exercise Periodic Breathing.

Some heart failure (HF) patients develop ventilatory oscillation which is composed of exercise periodic breathing (EPB) and sleep apnea. The ventilatory oscillation is associated with exercise intolerance. This study employed an integrated monitoring system to elucidate the way of central and peripheral hemodynamic adaption responding to exercise. This study recruited 157 HF patients to perform exercise testing using a bicycle ergometer. A noninvasive bio-reactance device was adopted to measure cardiac hemodynamics, whereas a near-infrared spectroscopy (NIRS) was used to assess perfusion and O2 extraction in the frontal cerebral lobe (FC) and vastus lateralis muscle (VL) during exercise respectively. Furthermore, quality of life (QoL) was measured with the Short Form-36 (SF-36) and the Minnesota Living with Heart Failure questionnaires (MLHFQ). The patients were divided into an EPB group (n = 65) and a non-EPB group (n = 92) according to their ventilation patterns during testing. Compared to their non-EPB counterparts, the patients with EPB exhibited 1) impaired aerobic capacity with a smaller peak oxygen consumption (VO2peak) and oxygen uptake efficiency slopes; 2) impaired circulatory and ventilatory efficiency with relatively high cardiac output and ventilation per unit workload; 3) impaired ventilatory/hemodynamic adaptation in response to exercise with elevated deoxyhemoglobin levels in the FC region; and 4) impaired QoL with lower physical component scores on the SF-36 and higher scores on the MLHFQ. In conclusion, EPB may reduce circulatory-ventilatory-hemodynamic efficiency during exercise, thereby impairing functional capacity in patients with HF.

Peripheral pulse harmonic analysis and its clinical application: A systematic review.

Introduction: Pulse harmonic analysis is a quantitative and objective methodology within traditional Chinese medicine (TCM) used to evaluate pulse characteristics. However, interpreting pulse wave data is challenging due to its inherent complexity. This study aims to provide a comprehensive review and comparison of existing human pulse wave harmonic analysis methods to elucidate their patterns and characteristics. Methods: A systematic review of clinical research reports published from 1990 to 2021 was conducted, focusing on variations in harmonic characteristics across different medical conditions and physiological states. Keyword searches included terms related to analysis methods (e.g., "Pulse Spectrum," "harmonic analysis," "harmonic index") and measured indicators (e.g., "vascular response," "PPG," "Photoplethysmography," "aortic," "arterial," "blood pressure"). Supplementary research using PubMed's Mesh terms specifically targeted "Pulse wave analysis" within the methods and statistical analysis domain. Articles were filtered based on predefined criteria, including human participants and research related to pulse pressure or vascular volume changes. Conference papers, animal studies, and irrelevant research were excluded, with literature evaluation scales selected based on the retrieved research reports. Results: Initially, 6487 research reports were identified, and after screening, 50 reports were included in the review. The analysis revealed that low-frequency harmonics increase following vigorous activity or sympathetic excitation but decrease during rest or parasympathetic excitation. Cardiovascular patients exhibited elevated first harmonics associated with the liver meridian, while diabetes patients displayed weakened third harmonics related to the spleen meridian. Liver dysfunction was linked to changes in the first harmonic, and cancer patients showed signs of liver and kidney yin deficiency in the first and second harmonics. These findings underscore the potential of harmonic analysis for TCM disease diagnosis and organ assessment. Moreover, individuals with conditions such as liver dysfunction, cancer, and gynecological disorders displayed distinct intensity patterns across harmonics one through ten compared to healthy controls, albeit with some variations. Heterogeneity in these studies mainly stemmed from differences in measurement methods and study populations. Additionally, research suggested that factors like blood circulation and cognitive activity influenced harmonic intensity. Conclusions: In summary, this report consolidates prior research on pulse wave harmonics analysis, revealing unique patterns associated with various physiological conditions. Despite limitations, such as limited sample sizes in previous studies, the observed associations between physiological states and harmonics hold promise for potential clinical applications. This study lays a solid foundation for future applications of arterial wave harmonics analysis, promoting wider adoption of this analytical approach.

Tongue feature dataset construction and real-time detection.

BACKGROUND: Tongue diagnosis in traditional Chinese medicine (TCM) provides clinically important, objective evidence from direct observation of specific features that assist with diagnosis. However, the current interpretation of tongue features requires a significant amount of manpower and time. TCM physicians may have different interpretations of features displayed by the same tongue. An automated interpretation system that interprets tongue features would expedite the interpretation process and yield more consistent results. MATERIALS AND METHODS: This study applied deep learning visualization to tongue diagnosis. After collecting tongue images and corresponding interpretation reports by TCM physicians in a single teaching hospital, various tongue features such as fissures, tooth marks, and different types of coatings were annotated manually with rectangles. These annotated data and images were used to train a deep learning object detection model. Upon completion of training, the position of each tongue feature was dynamically marked. RESULTS: A large high-quality manually annotated tongue feature dataset was constructed and analyzed. A detection model was trained with average precision (AP) 47.67%, 58.94%, 71.25% and 59.78% for fissures, tooth marks, thick and yellow coatings, respectively. At over 40 frames per second on a NVIDIA GeForce GTX 1060, the model was capable of detecting tongue features from any viewpoint in real time. CONCLUSIONS/SIGNIFICANCE: This study constructed a tongue feature dataset and trained a deep learning object detection model to locate tongue features in real time. The model provided interpretability and intuitiveness that are often lacking in general neural network models and implies good feasibility for clinical application.

Phytotherapeutic potential of compounds identified from fractionated extracts of Morus alba L., as an inhibitor of interleukin-6 in the treatment of rheumatoid arthritis: computational approach.

The presence of HLA-DRB1 alleles that encode critical points associated with environmental interactions is associated with increased risk of rheumatoid arthritis caused by anti-citrullinated protein antibodies. Therefore, interleukin-6 (IL-6), a multifunctional cytokine that controls both local and systemic acute inflammatory responses through its ability to induce a phase response, plays a serious role. Its overexpression leads to pathological challenges such as rheumatoid arthritis and menopausal osteoporosis. However, targeting the IL-6 receptor and its region could be the major step in controlling the overexpression of this cytokine for therapeutic importance. Therefore, our research explored the computational insight needed to investigate the anti-RFA potential of phytochemicals from fractionated extracts of Morus alba L. against receptors, which have been implicated as druggable targets for the treatment of rheumatoid arthritis. In this study, fifty-nine (59) previously isolated and characterized phytochemicals from M. alba L. were identified from the literature and retrieved from the PubChem database. In silico screening was used to assess the mode of action of these phytochemicals from M. alba L. against receptors that may serve as therapeutic targets for rheumatoid arthritis. Molecular docking studies, toxicity prediction, drug visualization and molecular dynamics simulation (MD) of the ligands together with the receptor-identified target were carried out using the Schrodinger Molecular Drug Discovery Suite. The findings indicated that a selected group of ligands displayed significant binding strength to specific amino acid residues, revealing an important link between the building blocks of proteins (amino acids) and ligands at the inhibitor binding site through traditional chemical interactions, such as interactions between hydrophobic and hydrogen bonds. The binding affinities of the receptors were carefully checked via comparison with those of the approved ligands, and the results suggested structural and functional changes in the lead compounds. Therefore, the bioactive component from M. alba L. could be a lead foot interleukin-6 (IL-6) inhibitor and could be a promising lead compound for the treatment of rheumatoid arthritis and related challenges.Communicated by Ramaswamy H. Sarma.

Identified phytocompounds from the fractionated extract of Morus alba inhibit IL-6 production via molecular docking and molecular simulation analysisChanges in the structure and function of these hit compounds show promising potential in the treatment of rheumatoid arthritis and related challenges.

In silico identification of compounds from Piper sarmentosum Roxb leaf fractionated extract inhibit interleukin-6 to prevent rheumatoid arthritis.

Objective: Medicinal herbs with a phytonutrient background has been applied globally as major alternatives to ameliorate the continuous increase in rheumatoid arthritis cases worldwide. We herein aimed to critically examine the bioactive components of the medicinal herb Piper sarmentosum Roxb leaf fractionated extract for its potential to inhibit the influx of interleukin-6 (IL-6) in rheumatoid arthritis. Methods: The Schrödinger platform was employed as the main computational acumen for the screening of bioactive compounds identified and reference compounds subjected to molecular simulation (MDS) for analyzing the stability of docked complexes to assess fluctuations and conformational changes during protein-ligand interactions. Results: The values of the simulatory properties and principal component analysis (PCA) revealed the good stability of these phytochemicals in the active pocket of interleukin-6 (IL-6). Discussion: Our findings reveal new strategies in which these phytochemicals are potential inhibitory agents that can be modified and further evaluated to develop more effective agents for the management of rheumatoid arthritis, thereby providing a better understanding and useful model for the reproduction and/or discovery of new drugs for the management of rheumatoid arthritis and its complications.