The efficacy and neural mechanism of acupuncture therapy in the treatment of visceral hypersensitivity in irritable bowel syndrome.

Irritable Bowel Syndrome (IBS) is a complex functional gastrointestinal disorder primarily characterized by chronic abdominal pain, bloating, and altered bowel habits. Chronic abdominal pain caused by visceral Hypersensitivity (VH) is the main reason why patients with IBS seek medication. Significant research effort has been devoted to the efficacy of acupuncture as a non-drug alternative therapy for visceral-hyperalgesia-induced IBS. Herein, we examined the central and peripheral analgesic mechanisms of acupuncture in IBS treatment. Acupuncture can improve inflammation and relieve pain by reducing 5-hydroxytryptamine and 5-HT3A receptor expression and increasing 5-HT4 receptor expression in peripheral intestinal sensory endings. Moreover, acupuncture can also activate the transient receptor potential vanillin 1 channel, block the activity of intestinal glial cells, and reduce the secretion of local pain-related neurotransmitters, thereby weakening peripheral sensitization. Moreover, by inhibiting the activation of N-methyl-D-aspartate receptor ion channels in the dorsal horn of the spinal cord and anterior cingulate cortex or releasing opioids, acupuncture can block excessive stimulation of abnormal pain signals in the brain and spinal cord. It can also stimulate glial cells (through the P2X7 and prokinetic protein pathways) to block VH pain perception and cognition. Furthermore, acupuncture can regulate the emotional components of IBS by targeting hypothalamic-pituitary-adrenal axis-related hormones and neurotransmitters via relevant brain nuclei, hence improving the IBS-induced VH response. These findings provide a scientific basis for acupuncture as an effective clinical adjuvant therapy for IBS pain.

Corrigendum: The effects of Tai Chi on physical function and safety in patients with rheumatoid arthritis: a systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fphys.2023.1079841.].

Pharmacological effects and mechanisms of paeonol on antitumor and prevention of side effects of cancer therapy.

Cancer represents one of the leading causes of mortality worldwide. Conventional clinical treatments include radiation therapy, chemotherapy, immunotherapy, and targeted therapy. However, these treatments have inherent limitations, such as multidrug resistance and the induction of short- and long-term multiple organ damage, ultimately leading to a significant decrease in cancer survivors' quality of life and life expectancy. Paeonol, a nature active compound derived from the root bark of the medicinal plant Paeonia suffruticosa, exhibits various pharmacological activities. Extensive research has demonstrated that paeonol exhibits substantial anticancer effects in various cancer, both in vitro and in vivo. Its underlying mechanisms involve the induction of apoptosis, the inhibition of cell proliferation, invasion and migration, angiogenesis, cell cycle arrest, autophagy, regulating tumor immunity and enhanced radiosensitivity, as well as the modulation of multiple signaling pathways, such as the PI3K/AKT and NF-κB signaling pathways. Additionally, paeonol can prevent adverse effects on the heart, liver, and kidneys induced by anticancer therapy. Despite numerous studies exploring paeonol's therapeutic potential in cancer, no specific reviews have been conducted. Therefore, this review provides a systematic summary and analysis of paeonol's anticancer effects, prevention of side effects, and the underlying mechanisms involved. This review aims to establish a theoretical basis for the adjunctive strategy of paeonol in cancer treatment, ultimately improving the survival rate and enhancing the quality of life for cancer patients.

NIR-II-absorbing diimmonium polymer agent achieves excellent photothermal therapy with induction of tumor immunogenic cell death.

Photothermal therapy has shown great promise for cancer treatment and second near-infrared (NIR-II) -absorbing particles could further improve its precision and applicability due to its superior penetration depth and new imaging ability. Herein, high NIR-II-absorbing polymer particles were prepared by using soluble isobutyl-substituted diammonium borates (P-IDI). The P-IDI showed stronger absorption at 1000-1100 nm, which exhibited excellent photostability, strong photoacoustic imaging ability and high photothermal conversion efficiency (34.7%). The investigations in vitro and in vivo demonstrated that the excellent photothermal effect facilitated complete tumor ablation and also triggered immunogenic cell death in activation of the immune response. The high solubility and excellent photothermal conversion ability demonstrated that polymer IDI particles were promising theranostic agents for treatment of tumors with minor side effects.

Mechanism of Tao Hong Decoction in the treatment of atherosclerosis based on network pharmacology and experimental validation.

Background: Atherosclerosis (AS) has long been recognized as a cardiovascular disease and stroke risk factor. A well-known traditional Chinese medicine prescription, Tao Hong decoction (THD), has been proven effective in treating AS, but its mechanism of action is still unclear. Objective: To assess the effects, explore THD's primary mechanism for treating AS, and provide a basis for rational interpretation of its prescription compatibility. Methods: Based on network pharmacology, we evaluated the mechanism of THD on AS by data analysis, target prediction, the construction of PPI networks, and GO and KEGG analysis. AutoDockTools software to conduct Molecular docking. Then UPLC-Q-TOF-MS was used to identify significant constituents of THD. Furthermore, an AS mice model was constructed and intervened with THD. Immunofluorescence, RT-qPCR, and Western blot were used to verify the critical targets in animal experiments. Results: The network pharmacology results indicate that eight core targets and seven core active ingredients play an essential role in this process. The GO and KEGG analysis results suggested that the mechanism is mainly involved in Fluid shear stress and atherosclerosis and Lipid and atherosclerosis. The molecular docking results indicate a generally strong affinity. The animal experiment showed that THD reduced plaque area, increased plaque stability, and decreased the levels of inflammatory cytokines (NF-κB, IL-1α, TNF-α, IL-6, IL-18, IL-1ß) in high-fat diet -induced ApoE-/-mice. Decreased levels of PTGS2, HIF-1α, VEGFA, VEGFC, FLT-4, and the phosphorylation of PI3K, AKT, and p38 were detected in the THD-treated group. Conclusion: THD plays a vital role in treating AS with multiple targets and pathways. Angiogenesis regulation, oxidative stress regulation, and immunity regulation consist of the crucial regulation cores in the mechanism. This study identified essential genes and pathways associated with the prognosis and pathogenesis of AS from new insights, demonstrating a feasible method for researching THD's chemical basis and pharmacology.

The effects of Tai Chi on physical function and safety in patients with rheumatoid arthritis: A systematic review and meta-analysis.

Background: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune disease that results in the destruction of joints, connective tissues, muscle, tendons and fibrous tissue. Until now, there are no cure therapies. Objective: We aimed to assess the effectiveness of Tai Chi (TC) on RA patients by meta-analysis. Methods: The PubMed, Cochrane Library, EMBASE, web of science, China National Knowledge Infrastructure and Google Scholar were searched up to January 2023. We included randomized controlled trials (RCTs) or controlled clinical trials (CCTs) comparing TC to control conditions for RA patients. Review Manager (Version 5.3) software was used to analyze outcomes of time to walk 50 feet, joint tenderness, number of swollen joints or tender joints, handgrip strength, pain, the Health Assessment Questionnaire (HAQ) and withdraws overall. Results: A total of 351 patients with RA from six RCTs and three CCTs were included for meta-analysis. TC could also significantly decrease withdrawals overall in studies (OR = 0.28, 95% CI 0.12 to 0.67, p = 0.002). No significant treatment effects of physical function were identified of the other outcomes. Conclusion: Our findings indicated that TC was safe to RA patients, but it cannot improve physical function and pain. However, there is still lack of more evidence. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=367498], identifier [CRD42022367498].

Hydroxysafflor yellow A regulates lymphangiogenesis and inflammation via the inhibition of PI3K on regulating AKT/mTOR and NF-κB pathway in macrophages to reduce atherosclerosis in ApoE-/- mice.

BACKGROUND: Macrophage-mediated inflammatory infiltration and pathological lymphangiogenesis around atherosclerotic plaques are newly highlighted treatment targets of atherosclerosis. Although the effect of Hydroxysafflor yellow A(HSYA) on atherosclerosis was clear, few studies focus on the regulation of HSYA on such mechanisms. PURPOSE: This study aimed to uncover the key site of HSYA on improving atherosclerosis by regulating macrophage-induced inflammation and lymphangiogenesis. STUDY DESIGN: This study was designed to explore the new mechanism of HSYA on alleviating atherosclerosis in vitro and in vivo. METHODS: We determined the expression of vascular endothelial growth factor C(VEGF-C) in Raw264.7 cells and high-fat diet fed ApoE knockout (ApoE-/-) mice. Raw264.7 cells were treated with HSYA under the stimulation of LPS and ox-LDL. HFD induced ApoE-/- mice were given different concentrations of HSYA-saline solution by tail vein injection and ATV-saline suspension by gavage. C57/B6j mice fed with chow diet were used for the control group. H&E, oil red O and immunofluorescence staining analysis were used for visualizing the pathological changes. The biological impact of HSYA was evaluated by body weight, lipid metabolism, inflammation levels, and corresponding function indexes of kidney and liver. RT-qPCR and western blot methods were conducted to determine the expression of the inflammation and lymphangiogenesis factors. Molecular docking and microscale thermophoresis analysis were used to verify the combination of HSYA and PI3K. RESULTS: In vivo, HSYA reduced the plaque formation, hepatic steatosis and inflammation-related lymphangiogenesis (IAL). It also changed the serum levels of inflammation (VEGF-C, TNF-α, IL-6, VCAM1, MCP1), lipid indexes (LDL, CHOL, TRIG) and relevant lymphangiogenesis (VEGF-C and LYVE-1) and inflammation (VCAM-1 and IL-6) signals in the aorta. In vitro, HSYA regulated Akt/mTOR and NF-κB activation by the inhibition of PI3K in macrophages. CONCLUSION: HSYA affects inflammation and inflammation-associated lymphangiogenesis via suppressing PI3K to affect AKT/mTOR and NF-B pathway activation in macrophages, showing a comprehensive protective effect on atherosclerosis.

Effects of Different Chemicals on Sexual Regulation in Persimmon (Diospyros kaki Thunb.) Flowers.

Research on crop sexuality is important for establishing systems for germplasm innovation and cultivating improved varieties. In this study, androecious persimmon trees were treated with various concentrations of ethrel (100, 500, and 1,000 mg/L) and zeatin (1, 5, and 10 mg/L) to investigate the morphological, physiological, and molecular characteristics of persimmon. Ethrel at 1,000 mg/L and zeatin at 10 mg/L both significantly reduced the stamen length and pollen grain diameter in androecious trees. Ethrel treatment also led to reduced stamen development with degenerated cellular contents; zeatin treatment promoted the development of arrested pistils via maintaining relatively normal mitochondrial morphology. Both treatments altered carbohydrate, amino acid, and endogenous phytohormone contents, as well as genes associated with hormone production and floral organ development. Thereafter, we explored the combined effects of four chemicals, including ethrel and zeatin, as well as zebularine and 5-azacytidine, both of which are DNA methylation inhibitors, on androecious persimmon flower development. Morphological comparisons showed that stamen length, pollen viability, and pollen grain diameter were significantly inhibited after combined treatment. Large numbers of genes involving in carbohydrate metabolic, mitogen-activated protein kinase (MAPK) signaling, and ribosome pathways, and metabolites including uridine monophosphate (UMP) and cyclamic acid were identified in response to the treatment, indicating complex regulatory mechanisms. An association analysis of transcriptomic and metabolomic data indicated that ribosomal genes have distinct effects on UMP and cyclamic acid metabolites, explaining how male floral buds of androecious persimmon trees respond to these exogenous chemicals. These findings extend the knowledge concerning sexual differentiation in persimmon; they also provide a theoretical basis for molecular breeding, high-yield cultivation, and quality improvement in persimmon.

Lycium barbarum polysaccharide protects ARPE­19 cells against H2O2­induced oxidative stress via the Nrf2/HO­1 pathway.

Age­related macular degeneration (AMD) is a global health problem. Lycium barbarum polysaccharide (LBP), a traditional Chinese herbal medicine, has been proven to be effective against several eye diseases. However, only a few studies have investigated the effectiveness of LBP for AMD. In the present study, the human retinal epithelial cell line, ARPE­19, was pretreated with LBP for 24 h before exposure to H2O2 (500 µM). Cell viability was assessed, and a series of oxidative and antioxidant indicators were evaluated to determine the influence of LBP on H2O2­triggered oxidative stress. The present study also determined the apoptosis status, as well as the expression levels of apoptotic proteins and nuclear factor erythroid 2­related factor 2 (Nrf2)/heme oxygenase­1 (HO­1) pathway proteins. The present study aimed to determine the protective role for LBP pretreatment and its underlying molecular mechanism. The results of the present study suggest that pretreatment of ARPE­19 cells with LBP exhibit high efficacy at reducing oxidative damage and inhibiting cell apoptosis. Furthermore, LBP may modulate the expression of proteins involved in the apoptotic pathway and activate the Nrf2 signaling pathway.

Tai Chi on bone mineral density of postmenopausal osteoporosis: A protocol for systematic review and meta-analysis.

BACKGROUND: Osteoporosis is a clinically common metabolic disease, especially in postmenopausal women. Tai Chi might be beneficial in osteoporosis patients. This study will be performed to examine the effects of Tai Chi on bone mineral density of postmenopausal osteoporosis. METHODS: We will search the electronical databases and hand-searching journals or reference lists. The study screening and data extraction will be carried out by 2 investigators independently. The primary outcome is bone mineral density (lumbar spine, Ward's triangle, trochanter, proximal femur, femoral neck, or total hip). Secondary outcomes are pain score, alkaline phosphatase, osteocalcin, and adverse effects. Review Manager V.5.3 software will be used to compute the data. RESULTS: The results of the study will provide a reliable evidence to assess the effects of Tai Chi on bone mineral density of postmenopausal osteoporosis. CONCLUSION: The conclusion of our systematic review will answer whether Tai Chi is an effective intervention to improve bone mineral density of postmenopausal osteoporosis.

Does omega-3 lower blood pressure?: A protocol for systematic review and meta-analysis.

BACKGROUND: Hypertension is a clinically common cardiovascular disease, resulting in many complications. Omega-3 might be beneficial in lowering blood pressure. This protocol will be performed to evaluate the effects of omega-3 on blood pressure in hypertensive patients. METHODS: We will search both the electronical databases and paper-published journals. Endnote software will be used to complete study screening and data extraction by 2 reviewers independently. Review Manager software will be used to synthesize the data. The primary outcomes are systolic blood pressure and diastolic blood pressure. Secondary outcome is the adverse effects. RESULTS: The results of this study will propose a trustworthy evidence to evaluate the effects of omega-3 on blood pressure of hypertensive patients. CONCLUSION: The conclusion of our systematic review will reply whether omega-3 is an effectual intervention to lower blood pressure of hypertensive patients. ETHICS: This review does not require ethical approval because all of the data analyzed in this review have been published. REGISTRATION NUMBER: INPLASY202070103 (DOI number: 10.37766/inplasy2020.7.0103).

Vitamin D for inflammation biomarkers in coronary artery disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Coronary artery disease (CAD) is a clinically common coronary heart disease. Vitamin D might be beneficial in CAD patients through its favorable effects on inflammation biomarkers. This study will be performed to examine the effects of Vitamin D supplementation on inflammatory markers in CAD patients. METHODS: We will search the electronical databases and hand-searching journals or reference lists. The study screening and data extraction will be carried out by 2 investigators independently. The primary outcome is inflammatory biomarkers of peripheral blood. Secondary outcomes are triglyceride, total cholesterol, high-density lipoprotein cholesterol levels, low-density lipoprotein cholesterol, and blood pressure. Review Manager (RevMan, version 5.3; The Nordic Cochrane Centre, Copenhagen, Denmark: http://community.cochrane.org) V.5.3 software will be used to compute the data. RESULTS: The results of the study will provide a reliable evidence to assess the efficacy of Vitamin D supplement on inflammation biomarkers of CAD patients. CONCLUSION: The conclusion of our systematic review will answer whether Vitamin D is an effective intervention to relieve inflammation of CAD patients. ETHICS: Because all of the data used in this review has been published, this review does not require ethical approval. REGISTRATION NUMBER: INPLASY202060072.

Music Intervention in Pain Relief of Cardiovascular Patients in Cardiac Procedures: A Systematic Review and Meta-analysis.

BACKGROUND: Numerous meta-analyses have been conducted on music and pain, but no studies have investigated music and cardiac procedural pain. OBJECTIVE: To assess the effects of music intervention on pain in cardiac procedures in the published randomized controlled trials. METHODS: This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All the included randomized controlled studies were published between 1999 and 2016. Studies were obtained from electronic databases or by hand-searching of related journals and reference lists. The main outcome was pain intensity, and the secondary outcomes were vital signs such as heart rate, respiration rate, systolic blood pressure, and diastolic blood pressure. Risk of bias of the included studies was evaluated according to the Cochrane Collaboration guidelines. RESULTS: Analysis of 14 studies indicated that music interventions had statistically significant effects on decreasing pain scales (mean deviation [MD] = -1.84), heart rate (MD = -2.62), respiration rate (MD = -2.57), systolic blood pressure (MD = -5.11), and diastolic blood pressure (MD = 0.44). The subgroup analysis method was used in all five outcomes. CONCLUSIONS: Considering all the possible benefits, music intervention may provide an effective complement for the relief of cardiac procedural pain.

Shi's Yi-Qi Bu-Shen Tong-Luo decoction combined with manipulation in the management of wrist stiffness after distal radius fracture: Study protocol clinical trial (SPIRIT Compliant).

INTRODUCTION: Wrist stiffness is a common sequela of distal radial fractures. Manipulation is generally used and effective, but problems exist, such as intense pain, swelling during the process of manipulation and long treatment period. Therefore, a combinative therapeutic strategy is necessary to benefit rehabilitation after distal radius fracture. Shi's Yi-Qi Bu-Shen Tong-Luo decoction (BTD) combined with wrist manipulation has been used in the Shanghai Ninth People's Hospital Huangpu Branch in last few decades. BTD has potential therapeutic effects on rehabilitation after distal radius fracture, which should be evaluated by rigorous clinical trial. METHODS/DESIGN: A randomized, double-blind, placebo-controlled clinical trial will be conducted to determine the efficiency of BTD in relief of wrist stiffness and pain and function rehabilitation. A total of 80 wrist stiffness patients with or without pain and edema will be enrolled, and treated with wrist manipulation plus BTD or placebo for 4 weeks. The primary outcome measure is the Cooney wrist score. The second outcome measures include pain numerical rating scale, patient rated wrist evaluation, 36-item short form health survey questionnaire, and side effects. DISCUSSION: Although BTD has shown effects on rehabilitation after distal radius fracture in the Shanghai Ninth People's Hospital Huangpu Branch for decades, the universality of this efficacy needs evaluated. The results of this trial will provide a convincing evidence. TRIAL REGISTRATION: ChiCTR2000029260, January 19, 2020.

A multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of Taoren Honghua Jian granule in patients with stable coronary artery disease.

INTRODUCTION: Stable coronary artery disease (SCAD) is a common clinical style in patients with coronary artery disease. Inflammation and immune injury in SCAD have been proven. Current interventions can relieve patients' symptoms, but none are stable to improve the immune damage significantly. Chinese herb is used to treat stable angina pectoris as an alternative therapy. Taoren Honghua Jian granule (THJG) is a classical formula from which patients can benefit, but lack convincing evidence. Therefore, we report a protocol of high-quality randomized controlled trial. METHODS/DESIGN: We will conduct a randomized, double-blind, placebo-controlled clinical trial to assess the effect of THJG in relief of symptoms and blood immune indexes. A total of 80 patients with SCAD will be enrolled, and treated with THJG or placebo for 4 weeks. The primary outcome measurement is change of integral traditional Chinese medicine (TCM) syndrome score from baseline to 4 weeks' treatment. The 2nd outcome measurements include change of integral TCM syndrome scores from baseline to 2 weeks' treatment and another 4 weeks' follow-up, inflammation indexes at baseline and 4 weeks' treatment. It also includes Seattle Angina Questionnaire, major adverse cardiovascular events, Athens Insomnia scale, and 36-item short form health survey score from baseline to 2 weeks' and 4 weeks' treatment, and another 4 weeks' follow-up. Adverse events will be evaluated throughout the trial. DISCUSSION: The results of this trial will prove whether THJG could alleviate symptoms, control inflammation, and improve quality of life in patients with SCAD. TRIAL REGISTRATION: ChiCTR1900021772, registered 8 March, 2019.

[Effect of HPMCAS/curcumin amorphous solid dispersion in enhancing dissolution and chemical stability of curcumin].

To enhance in vitro dissolution of Cur by preparing Cur solid dispersions. The ability of HPMCAS-HF,HPMCAS-MF,HPMCAS-LF and PVPK30 to maintain supersaturated solution was investigated by supersaturation test. Amorphous solid dispersions were prepared by the solvent-evaporation method. The prepared samples were characterized using infrared spectroscopy( IR) and differential scanning calorimetry( DSC),and in vitro dissolution was investigated. DSC and IR results showed that in 1 ∶3 and 1 ∶9 solid dispersions,Cur was amorphously dispersed in the carrier,and the interaction existed between drug and carrier. The supersaturation test showed that the order of the ability of polymer to inhibit crystallization of Cur was MF>HF>LF>K30. The dissolution results showed that Cur-K30 amorphous solid dispersion had the highest drug release rate; Cur-K30 and Cur-LF amorphous solid dispersions had a quicker but not stable dissolution rate,and the drug concentration decrease after 4 h; Cur-MF and Cur-HF solid dispersions had a low dissolution,which however increased steadily,attributing to the strong ability of the polymers to inhibit the crystallization of Cur. HPMCAS could inhibit the degradation of Cur better than K30,especially MF and HF. The amorphous solid dispersions of cur significantly enhanced the dissolution of Cur and improved the chemical stability of Cur. This study can provide a basis for the rational selection of the polymer used for Cur solid dispersion.

A multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of Huangqi Guizhi Wuwutang granule in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by swelling, pain, and synovial damage. Effective methods lack in the treatment of RA. A traditional prescription in use for thousands of years in China, Huangqi Guizhi Wuwutang granule (HGWG) is still chosen to relieve pain and prevent joint malformation in RA patients. However, no evidence-based medical research has been organized to assess the effectiveness and safety of HGWG for RA. METHODS/DESIGN: We will conduct a multicenter, randomized, double-blind, placebo-controlled clinical trial to determine whether HGWG can relieve pain and protect joints. We will randomly divide 120 patients with active RA into 2 groups, treated for 12 weeks. Main measurement is the rate of ACR50 score (American College of Rheumatology) from the baseline to 12 weeks. Secondary measurements include rate of ACR20/70, change of Disease Activity Score (DAS) 28, Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient Assessment of Arthritis Pain, Patient Global Assessment of Arthritis, and AIS score. The time points are set as baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, and 48 weeks. In addition, the rate of ACR50 from the baseline to 2 weeks, 4 weeks, 8 weeks, 24 weeks, and 48 weeks' follow-up are also the secondary outcome measures. DISCUSSION: The findings of this research will elucidate the efficacy and safety of HGWG and provide an alternative treatment for RA. In addition, our data will benefit the clinical decision-making on active RA and possibly be incorporated into future guidelines. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03593837.

Betaine protects against heat exposure-induced oxidative stress and apoptosis in bovine mammary epithelial cells via regulation of ROS production.

Heat stress is one of the wide varieties of factors which cause oxidative stress in vivo; elevated temperature can lead to oxidative stress of dairy cows that affects milk production. The aim of this study was to determine the capacity of the betaine to act as an antioxidant against oxidative stress induced by heat exposure and apoptosis in mammary epithelial cells (mammary alveolar cells, MAC-T). The MAC-T were divided into four treatment groups: control (37 °C), heat stress (HS, 42 °C), betaine (37 °C), and HS + betaine. MAC-T under heat stress (HS) showed increased ROS accumulation, malondialdehyde (MDA) content, superoxide dismutase (SOD) concentration, and catalase (CAT) activity. During heat stress, betaine decreased the mRNA expression level of HSP70 and HSP27 in MAC-T. Bax/Bcl-2 ratio and caspase-3, the markers of apoptosis, were also elevated in MAC-T under heat stress. The markers of oxidative stress Nrf-2/HO-1 genes were also elevated in MAC-T under heat stress. Pretreatment of betaine reversed the heat-induced depletion in total antioxidant status, ROS accumulation, and SOD and CAT contents in MAC-T. Bax/Bcl-2 ratio and Nrf-2/HO-1 expression of heat-exposed MAC-T were also reduced with betaine supplementation. In conclusion, betaine alleviated oxidative stress and apoptosis of MAC-T by inhibiting ROS accumulation.

The efficacy of the traditional Chinese medicine Jia Wei Niu Bang Zi granule combined with methotrexate in treating active rheumatoid arthritis: A multicenter, randomized, double-blinded controlled clinical trial.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic and autoimmune inflammatory disease ending with the destruction of joints. Current therapies can relieve RA symptoms, but some also bring severe adverse events. Therefore, an effective and safe therapeutic strategy remains to be created to benefit patients with RA by large. Jia Wei Niu Bang Zi granule (NBZG) consisting of RA-fighting Chinese herbals has been used in Longhua Hospital in the last several decades. NBZG has potential therapeutic effect on RA, which should be evaluated by larger sample clinical trial. METHODS: A multicenter, randomized, double-blind, placebo-controlled clinical trials will be conducted to determine the efficiency of NBZG in pain relief and joint protection. A total of 120 patients with active RA will be enrolled, and treated with NBZG or placebo for 12 weeks. The primary outcome measurements include rate of American College of Rheumatology (ACR) 50 at 12 weeks' treatment. The 2nd outcome measurements include rate change of ACR20, ACR70, the disease activity score (DAS) 28, 36-item Short-Form Health Survey Questionnaire, Health Assessment Questionnaire - Disability Index, score changes of Patient Assessment of Arthritis Pain, Patient Global Assessment of Arthritis, and the Athens insomnia scale at the same time points. DISCUSSION: Although NBZG has shown efficacy in treating RA in Longhua Hospital for decades, the universality of this efficacy needs evaluated. The results of this trial will provide a convincing evidence about NBZG's efficacy in treating active RA in a large population. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03173040 (registered on May 30, 2017).

The Cotton High-Affinity K+ Transporter, GhHAK5a, Is Essential for Shoot Regulation of K+ Uptake in Root under Potassium Deficiency.

Potassium (K) deficiency is a key limiting factor in cotton (Gossypium hirsutum) production. By grafting two contrasting cotton cultivars, CCRI41 (more susceptible to K+ deficiency) and SCRC22 (more tolerant of K+ deficiency), we established that cotton shoot plays a vital role in the regulation of root K+ uptake. To identify the genetic basis of this finding, we performed RNA sequencing (RNA-seq) of roots of CCRI41 self-grafts (CCRI41/CCRI41, scion/rootstock) and SCRC22/CCRI41 reciprocal-grafts exposed to K+ deficiency. We found that GhHAK5a, an orthologous of Arabidopsis thaliana high-affinity K+ transporter, AtHAK5, was significantly induced in the CCRI41 rootstock by the SCRC22 scion. This gene was mainly expressed in roots and was more highly induced by K+ deficiency in roots of SCRC22 than those of CCRI41. Agrobacterium-mediated virus-induced gene silencing and yeast complementary assay showed that GhHAK5a is a high-affinity K+ uptake transporter. Importantly, silencing of GhHAK5a in the CCRI41 rootstock almost completely inhibited the K+ uptake induced by SCRC22 scion in CCRI41 rootstock. We identified a key high-affinity K+ transporter, GhHAK5a in cotton, which is the essential target for shoot regulation of root K+ uptake under K+ deficiency.