Effects of the elongated needling combined with routine acupuncture therapy in the patients with post-stroke hemiplegia and central pain： a randomized controlled trial. / èŠ’é’ˆé€åˆºè”åˆä½“é’ˆæ²»ç–—å¯¹ä¸­é£ŽåŽåç˜«ä¼´ä¸­æž¢æ€§ç–¼ç—›æ‚£è€ çš„ä¸´åºŠç–—æ•ˆè§‚å¯Ÿï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To investigate the effects of the elongated needling at the points of hand and foot yang meridians and the Governor Vessel combined with the routine acupuncture therapy on pain, balance function and muscle strength of the patients with post-stroke hemiplegia and central post-stroke pain (CPSP), and to investigate whether its therapeutic mechanism is related to antioxidant damage. METHODS: Ninety-four patients with post-stroke hemiplegia and CPSP admitted from March 2020 to September 2021 were divided into a trial group (47 cases, 1 cases dropped out) and a control group (47 cases 3 cases dropped out). In the control group, the rehabilitation exercise combined with routine acupuncture therapy was used, and in the trial group, on the base of the treatment as the control group, the elongated needling at the points of hand and foot yang meridians and the Governor Vessel was supplemented. In the two groups, the treatment was given once daily, and 1 course of treatment was composed of 14 days, a total of 6 courses were required in the trial. Separately, before treatment, and 1, 2 and 3 months after treatment, between two groups, the score of visual analogue scale (VAS) and that of Berg balance scale (BBS), as well as muscle strength were compared；the neural function was evaluated using the national institutes of health stroke scale (NIHSS) and the serum contents of nitricoxide synthase (NOS), superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by ELISA in the patients. RESULTS: Compared with those before treatment, VAS score and NIHSS score were all decreased (P<0.05) in the trial and the control group after 1 month, 2 months and 3 months of treatment, and BBS score was increased (P<0.05)；and the case proportion of muscle strength grade 4 and 5 was higher (P<0.05) in the trial group. In the control group, the proportion of grade 4 increased after treatment for 2 months (P<0.05), and that of grade 4 and 5 increased after treatment for 3 months (P<0.05). The serum contents of NOS and SOD were increased (P<0.05), and MDA was decreased (P<0.05) after 3 months of treatment in the two groups. In comparison with the control group at the same time point, VAS score and NIHSS score were lower (P<0.05), BBS score higher (P<0.05) and the muscle strength grade was improved (P<0.05, P<0.01) after 1, 2 and 3 months of treatment, respectively；and the serum contents of NOS and SOD increased (P<0.05), and MDA decreased (P<0.05) after 3 months of treatment in the trial group. CONCLUSIONS: The elongated needling at the points of hand and foot yang meridians and the Governor Vessel, combined with the routine acupuncture therapy alleviates CPSP, improves balance and muscle strength and promotes the recovery of neural function in the patients with post-stroke hemiplegia, the mechanism may be related to antioxidant damage.

A Hybrid Nanoadjuvant Simultaneously Depresses PD-L1/TGF-ß1 and Activates cGAS-STING Pathway to Overcome Radio-Immunotherapy Resistance.

Currently, certain cancer patients exhibit resistance to radiotherapy due to reduced DNA damage under hypoxic conditions and acquired immune tolerance triggered by transforming growth factor-ß1 (TGF-ß1) and membrane-localized programmed death ligand-1 (PD-L1). Meanwhile, cytoplasm-distributed PD-L1 induces radiotherapy resistance through accelerating DNA damage repair (DDR). However, the disability of clinically used PD-L1 antibodies in inhibiting cytoplasm-distributed PD-L1 limits their effectiveness. Therefore, a nanoadjuvant is developed to sensitize cancer to radiotherapy via multi-level immunity activation through depressing PD-L1 and TGF-ß1 by triphenylphosphine-derived metformin, and activating the cGAS-STING pathway by generating Mn2+ from MnO2 and producing more dsDNA via reversing tumor hypoxia and impairing DDR. Thus, Tpp-Met@MnO2@Alb effectively enhances the efficiency of radiotherapy to inhibit the progression of irradiated local and abscopal tumors and tumor lung metastases, offering a long-term memory of antitumor immunity without discernible side effects. Overall, Tpp-Met@MnO2@Alb has the potential to be clinically applied for overcoming radio-immunotherapy resistance.

Understanding base and backbone contributions of phosphorothioate DNA for molecular recognition with SBD proteins.

Bacterial DNA phosphorothioate (PT) modification provides a specific anchoring site for sulfur-binding proteins (SBDs). Besides, their recognition patterns include phosphate links and bases neighboring the PT-modified site, thereby bringing about genome sequence-dependent properties in PT-related epigenetics. Here, we analyze the contributions of the DNA backbone (phosphates and deoxyribose) and bases bound with two SBD proteins in Streptomyces pristinaespiralis and coelicolor (SBDSco and SBDSpr). The chalcogen-hydrophobic interactions remained constantly at the anchoring site while the adjacent bases formed conditional and distinctive non-covalent interactions. More importantly, SBD/PT-DNA interactions were not limited within the traditional "4-bp core" range from 5'-I to 3'-III but extended to upstream 5'-II and 5'-III bases and even 5''-I to 5''-III at the non-PT-modified complementary strand. From the epigenetic viewpoint, bases 3'-II, 5''-I, and 5''-III of SBDSpr and 3'-II, 5''-II, and 5''-III of SBDSco present remarkable differentiations in the molecular recognitions. From the protein viewpoint, H102 in SBDSpr and R191 in SBDSco contribute significantly while proline residues at the PT-bound site are strictly conserved for the PT-chalcogen bond. The mutual and make-up mutations are proposed to alter the SBD/PT-DNA recognition pattern, besides additional chiral phosphorothioate modifications on phosphates 5'-II, 5'-II, 3'-I, and 3'-II.

Mume Fructus (Prunus mume Sieb. et Zucc.) extract accelerates colonic mucosal healing of mice with colitis induced by dextran sulfate sodium through potentiation of cPLA2-mediated lysophosphatidylcholine synthesis.

BACKGROUND: Mume Fructus (MF) is the fruit of Prunus mume Sieb. et Zucc, a plant of Rosaceae family. Previous studies demonstrated that MF was capable of ameliorating ulcerative colitis (UC) in mice, its action mechanism needs to be clarified. PURPOSE: This study deciphered whether and how MF extract accelerates colonic mucosal healing, the therapeutic endpoint of UC. METHODS: Biochemical, histopathological and qRT-PCR analyses were utilized to define the therapeutic efficacy of MF on dextran sulfate sodium (DSS)-induced colitis in mice. UHPLC-QTOF-MS/MS-based metabolomics technique was adopted to explore the changes of endogenous metabolites associated with UC and responses to MF intervention. qRT-PCR analysis was performed to confirm the molecular pathway in vivo. The effects of MF and lysophosphatidylcholine (LPC) on cell viability, wound healing, proliferation, and migration were examined through a series of in vitro experiments. Moreover, the effects of different subtypes of phospholipase A2 (PLA2) inhibitors on MF-treated colonic epithelial cells were detected by wound healing test and transwell assay. RESULTS: Orally administered MF could alleviate colitis in mice mainly by accelerating the healing of colonic mucosa. Guided by an unbiased metabolomics screen, we identified LPC synthesis as a major modifying pathway in colitis mice after MF treatment. Notably, MF facilitated the synthesis of LPC by enhancing the expression of PLA2 in colitis mice. Mechanistically, MF and LPC accelerated wound closure by promoting cell migration. Moreover, the promotion of MF on wound healing and migration of colonic epithelial cells was blunted by a cytosolic phospholipase A2 (cPLA2) inhibitor. CONCLUSION: MF can facilitate colonic mucosal healing of mice with colitis through cPLA2-mediated intestinal LPC synthesis, which may become a novel therapeutic agent of UC.

[Research progress in targeting autophagy of traditional Chinese medicine and natural compounds to regulate atherosclerosis].

Atherosclerosis(AS) is the common pathological basis of many ischemic cardiovascular diseases, and its formation process involves various aspects such as vascular endothelial injury and platelet activation. Vascular endothelial injury is the initiating factor of AS plaque. Monocytes are recruited to differentiate into macrophages at the damaged endothelial cells, which absorb oxidized low-density lipoprotein(ox-LDL) and slowly transform into foam cells. Smooth muscle cells(SMCs) proliferate and migrate continuously. As the only cell producing interstitial collagen fibers in the fibrous cap, SMCs largely determine whether the plaque ruptured or not. The amplifying inflammatory response during the formation of AS recruits platelets to adhere to the damaged area of vascular endothelium and stimulates excessive platelet aggregation. Autophagy activity is associated with vascular lesions and abnormal platelet activation, and excessive autophagy is considered to be a negative factor for plaque stability. Therefore, precise regulation of different types of vascular autophagy and platelet autophagy to treat AS may provide a new therapeutic perspective for the prevention and treatment of atherosclerotic ischemic cardiovascular disease. Currently, treatment strategies for AS still focus on lowering lipid levels with high-intensity statins, which often cause significant side effects. Therefore, the development of safer and more effective drugs and treatment modes is the focus of current research. Traditional Chinese medicine and natural compounds have the potential to treat AS by targeted autophagy, and have been playing an increasingly important role in the prevention and treatment of cardiovascular diseases in China. This paper summarizes the experimental studies on different vascular cell types and platelet autophagy in AS, and sums up the published research results on targeted autophagy of traditional Chinese medicine and natural plant compounds to regulate AS, providing new ideas for further research.

Effect of Hyperbaric Oxygen Therapy on the Survival Rate of Autologous Fat Transplantation.

OBJECTIVE: To investigate whether hyperbaric oxygen therapy can improve the survival rate of fat transplantation and analyze the possible mechanisms. METHODS: Ninety SD rats were randomly divided into 3 groups. All the rats were cut into pieces with about 5 mL of fat from the abdominal cavity, rinsed with normal saline for 3 times, and cleaned with cotton pad adsorption method. Then, 3 ml was removed, divided into 3 parts, and injected into three adjacent but not touching parts of the back. Group A received 1h/d hyperbaric oxygen therapy, group B received 2 h/d hyperbaric oxygen therapy, and group C received no hyperbaric oxygen therapy. The hyperbaric oxygen therapy lasted for 10 consecutive days. Fat grafts from one site were randomly removed at 2, 4, and 6 weeks after surgery, respectively. ① the survival rate of fat transplantation in three groups was compared. ② observe the pathological section; ③ immunohistochemistry was used to detect and compare the expression of vascular endothelial growth factor. RESULTS: The survival rate of fat transplantation in group A was the highest. After subcutaneous transplantation of 1 ml of fat and 1 hour/day of continuous hyperbaric oxygen treatment for 10 days, the fat survival rates were 0.796 ± 0.071 ml, 0.644 ± 0.151 ml, and 0.473 ± 0.127 ml at the second, fourth, and sixth weeks, respectively. The survival rate of fat transplantation in group B was the second. After subcutaneous transplantation of 1 ml of fat and 2 hour/day of continuous hyperbaric oxygen treatment for 10 days, the survival rate of fat was 0.624 ± 0.220 ml, 0.494 ± 0.125 ml, and 0.329 ± 0.153 ml at the second, fourth, and sixth weeks, respectively. The survival rate of fat transplantation in group C was the lowest. After subcutaneous transplantation of 1 ml of fat and no hyperbaric oxygen treatment for 10 days, the fat survival rates were 0.461 ± 0.132 ml, 0.290 ± 0.112 ml and 0.169 ± 0.091 ml at the second, fourth, and sixth weeks, respectively. We have made changes in the abstract of the article and marked in red color. CONCLUSION: Hyperbaric oxygen therapy is conducive to the survival of transplanted fat. Importantly, a short period of hyperbaric oxygen therapy (1 h/d) can promote the survival of transplanted fat. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Research progress in targeting autophagy of traditional Chinese medicine and natural compounds to regulate atherosclerosis / 中国中药杂志

Atherosclerosis(AS) is the common pathological basis of many ischemic cardiovascular diseases, and its formation process involves various aspects such as vascular endothelial injury and platelet activation. Vascular endothelial injury is the initiating factor of AS plaque. Monocytes are recruited to differentiate into macrophages at the damaged endothelial cells, which absorb oxidized low-density lipoprotein(ox-LDL) and slowly transform into foam cells. Smooth muscle cells(SMCs) proliferate and migrate continuously. As the only cell producing interstitial collagen fibers in the fibrous cap, SMCs largely determine whether the plaque ruptured or not. The amplifying inflammatory response during the formation of AS recruits platelets to adhere to the damaged area of vascular endothelium and stimulates excessive platelet aggregation. Autophagy activity is associated with vascular lesions and abnormal platelet activation, and excessive autophagy is considered to be a negative factor for plaque stability. Therefore, precise regulation of different types of vascular autophagy and platelet autophagy to treat AS may provide a new therapeutic perspective for the prevention and treatment of atherosclerotic ischemic cardiovascular disease. Currently, treatment strategies for AS still focus on lowering lipid levels with high-intensity statins, which often cause significant side effects. Therefore, the development of safer and more effective drugs and treatment modes is the focus of current research. Traditional Chinese medicine and natural compounds have the potential to treat AS by targeted autophagy, and have been playing an increasingly important role in the prevention and treatment of cardiovascular diseases in China. This paper summarizes the experimental studies on different vascular cell types and platelet autophagy in AS, and sums up the published research results on targeted autophagy of traditional Chinese medicine and natural plant compounds to regulate AS, providing new ideas for further research.

A randomized controlled trial of the influence of yoga for women with symptoms of post-traumatic stress disorder.

BACKGROUND: Survivors in motor vehicle accident (MVA) may have posttraumatic stress disorder (PTSD). Yoga is a complementary approach for PTSD therapy. METHODS: This randomized controlled trial explored whether yoga intervention has effects on reducing the symptoms of PTSD in women survived in MVA. Participants (n = 94) were recruited and randomized into control group or yoga group. Participants attended 6 45-minuite yoga sessions in 12 weeks. Depression Anxiety Stress Scales (DASS) and Impact of Events Scale-Revised (IES-R) were used to assess psychological distress. RESULTS: Post-intervention IES-R total score of yoga group was significantly lower than that of control group (p = 0.01). At both post-intervention and 3-months post intervention, the DASS-21 total scores of yoga group were both significantly lower than those of control group (p = 0.043, p = 0.024). Yoga group showed lower anxiety and depression level compared to control group at both post-intervention (p = 0.033, p < 0.001) and post-follow-up (p = 0.004, p = 0.035). Yoga group had lower levels of intrusion and avoidance compared to control group after intervention (p = 0.002, p < 0.001). CONCLUSION: Results illustrate that yoga intervention may alleviate anxiety and depression and improve the symptoms of PTSD in women with PTSD following MVA.

Effect of hyperbaric oxygen therapy on weight loss and hyperlipidemia in rats.

OBJECTIVE: To explore whether hyperbaric oxygen therapy(HBO) can promote weight loss and recovery of hyperlipidemia in rats, and to explore the possible mechanism. METHODS: 180 SD rats were divided into 6 groups with 30 rats in each group. The first 3 groups were intraperitoneally injected with fat emulsion to make hyperlipidemia models, and the last three groups were injected with normal saline. The first three groups received 3 h/d, 6 h/d, 0 h/d HBO therapy respectively, and the last three groups received the same treatment. Body weight, blood lipid and transaminase were measured in all SD rats, and pathological sections of heart, liver and kidney were observed. RESULTS: Hyperlipidemia group treated with 3 h/d hyperbaric oxygen has the effect of reducing hyperlipidemia compared with other groups and has the effect of heart and kidney protection. Although 6 h/d HBO therapy has a more noticeable effect on lowering hyperlipidemia, it has more apparent liver damage effects. The normal group treated with HBO for 3 h/d or 6 h/d both have the effect of weight loss, and the impact of liver injury is not apparent. However, the 6 h/d HBO therapy group had a more prominent weight loss effect. CONCLUSION: HBO therapy can promote weight loss and reduce hyperlipidemia. Our experiments have shown that 6 h/d and 3 h/d HBO therapy reduces blood lipids in hyperlipidemia SD rats. However, the former has noticeable liver damage effects on SD rats, and the latter is adequate for protecting the liver in normal or hyperlipidemia SD rats. At the same time, it has been proved that HBO therapy has cardio and kidney protection in hyperlipidemia SD rats.

Effect of Oral Vitamin D3 Supplementation in Exclusively Breastfed Newborns: Prospective, Randomized, Double-Blind, Placebo-Controlled Trial.

Exclusively breastfed infants are at a high risk of vitamin D deficiency. Few studies have evaluated the effects of vitamin D supplementation. Hence, we conducted a prospective randomized controlled trial investigating the effects of oral vitamin D3 400 IU/d supplementation in exclusively breastfed newborns. Serum 25-hydroxy-vitamin D (25[OH]D) levels in pregnant women and their newborns were evaluated. Breastfed newborns were randomized to one of two regimens at age 10 days. One group received vitamin D3 supplementation at a dose of 400 IU/d (vD-400 group), whereas the placebo group received a liquid product without vitamin D3. Outcomes were assessed at 4 months of age. A total of 92 pregnant women and their infants were enrolled, and the data of 72 infants (37 in the vD-400 group and 35 in the placebo group) who completed the study at 4 months of age were assessed. The results showed severe vitamin D deficiency in 15.2% of mothers before delivery, while 54.3% had vitamin D deficiency. Moreover, 15.2% of newborns presented with severe vitamin D deficiency at birth, while 52.2% had vitamin D deficiency. Maternal vitamin D levels were significantly correlated with infant vitamin D levels at birth (r = 0.816, p < 0.001). At 4 months of age, weight, head circumference, serum 25(OH)D, phosphorus, and intact parathyroid hormone levels significantly differed between the vD-400 and placebo groups. However, the body length and bone mineral density of the two groups did not differ significantly. Regardless of vitamin D supplementation, participants with severe vitamin D deficiency had significantly higher intact parathyroid hormone levels and lower bone mineral content. In conclusion, among exclusively breastfed infants, oral supplementation with vitamin D3 at a dose of 400 IU/d from age 10 days increased 25(OH)D concentrations at 4 months of age, but it did not affect bone mineralization. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Exploring the effects of artesunate and fuzheng huayu decoction on mitochondria in the treatment of schistosomiasis liver fibrosis / 中华肝脏病杂志

Objective: To compare the effects of artesunate (Art) and fuzheng huayu decoction on mitochondrial autophagy in the treatment of schistosomiasis liver fibrosis. Methods: Eighty C57BL/6 female mice were randomly divided into healthy control group, infection group, Art treatment group and Fuzheng Huayu Decoction treatment group, with 20 mice in each group. Mice in the infection group and treatment group were infected with 16 Schistosoma japonicum cercariae. After 6 weeks, praziquantel (300 mg/kg) was used for 2 days to kill the worms. The Art treatment group was treated with intraperitoneal injection of 100 mg/kg/day, while the Fuzheng Huayu Decoction treatment group was fed 16g of fuzheng huayu decoction per 1kg per day. After 6 weeks, fresh liver tissues of the four groups were collected. Masson staining and Western blot were used to observe the succinate dehydrogenase subunit A (SDHA) and malate dehydrogenase (MDH2), citrate synthase (CS), ketoglutarate dehydrogenase (OGDH), and target of rapamycin 1 (mTORC1) pathway involved in mitochondrial tricarboxylic acid cycle in liver tissues. The relative expression levels of adenylate activated protein kinase (AMPK) and mitochondrial autophagy pathway kinase (PINK1) were detected. Liver tissue samples were extracted from each group to detect the mitochondrial oxygen consumption rate. Two-way ANOVA was used to compare the significance and difference between two sets of samples. Results: Masson staining showed that the infection group mice had significantly higher liver fibrosis area than the healthy control group, while the Art treatment group and Fuzheng Huayu Decoction treatment group mice had lower liver fibrosis area than the infection group. Western blot analysis showed that the infection group (0.82 ± 0.05) had significantly lower relative expression of SDHA protein than the healthy control group (1.00 ± 0.05) (t = 11.23, P = 0.0035), while the Art treatment group (0.73 ± 0.05) had significantly higher relative expression of SDHA protein than the infection group (t = 10.79, P = 0.0073). However, there was no significant change in Fuzheng Huayu Decoction treatment group (0.98±0.05) (t = 1.925, P = 0.1266). The relative expression of p-AMPK protein was significantly higher in the infection group (1.15 ±0.05) than in the healthy control group (0.98 ± 0.07, t = 12.18, P = 0.0029), and the expression of p-AMPK in the Art treatment group (0.50 ± 0.05) was significantly lower than the infection group (t = 11.78, P = 0.0032). The relative protein expression of AMPK was significantly lower in the infection group (0.80 ± 0.05) than in the healthy control group (1.00 ± 0.05, t = 10.53, P = 0.0046). The expression of AMPK was significantly lower in the Art treatment group (0.54 ± 0.05) than in the infection group (T = 13.98, P = 0.0036). The relative expression of p-mTORC1 protein (0.93 ± 0.08) was not significantly different in the infection group than in the healthy control group (t = 2.28, P = 0.065), while the Art treatment group (0.63 ± 0.05) had significantly lower relative expression of p-mTORC1 protein than the infection group (t = 10.58, P = 0.029). The expression of p-mTORC1/ m-TORC1 was not significantly different in the infection group (0.98 ± 0.03) than in the healthy control group (0.97 ± 0.03, t = 0.98, P = 0.085), while the Art treatment group (0.63 ± 0.05) had significantly lower relative expression of p-mTORC1/ m-TORC1 than the infection group (t = 14.58, P = 0. 009). The relative protein expression of PINK1 was significantly lower in the infection group (0.55 ± 0.05) than in the healthy control group (1.00 ± 0.03, t = 13.49, P = 0.0011), while the Art treatment group (1.21 ± 0.05, t = 9.98, P = 0.0046) and Fuzheng Huayu Decoction treatment group (1.31 ±0.35, t = 6.98, P = 0.027) had significantly higher relative protein expression of PINK1 than the infection group. Mitochondrial function tests showed that after adding substrate complex II, the oxygen consumption of the infection group was lower than the healthy control group, while the Art treatment group and the Fuzheng Huayu Decoction treatment group had higher oxygen consumption than the infection group. The oxygen consumption was significantly lower after adding the substrate complex III in the infection group than the healthy control group, while the Art treatment group and Fuzheng Huayu Decoction treatment group had higher oxygen consumption than the infection group. Conclusion: Art can alleviate schistosomiasis liver fibrosis by inhibiting AMPK/mTORC1 signaling pathway activity and enhancing mitochondrial oxygen consumption, autophagy and SDHA expression.

Chai Hu oral liquid enhances the immune functions of both spleen and bursa of Fabricius in heat-stressed broilers through strengthening TLR4-TBK1 signaling pathway.

Heat stress can affect the poultry production and immune status of broilers. Heat stress disrupts intestinal integrity and increases intestinal inflammation, which is related with body immune dysfunction. Chai Hu oral liquid used as an antipyretic and anti-inflammatory drug is widely used in exogenous fever of poultry, but its resistance to heat stress and the mechanism is still unclear. In this study, a chronic heat stressed broilers model was established to explore the mechanisms of broilers' immune function changes and the effects of Chai Hu oral liquid. In this study, a total of 480 broilers were randomly divided into 6 groups with 80 replicates. Heat stress (HS) group broilers were stressed at 35 ± 2°C for 5 or 10 consecutive d with 6 h/d. Heat stressed (for 5 or 10 d) broilers were given with Jieshu KangreSan (Positive), Chai Hu oral liquid high, middle and low dosage (CH-High, CH-Mid, CH-Low) by oral administration. Birds in control group were treated with the same volume of PBS only in 25 ± 2°C. All birds were sacrificed at last heat stress challenged day. Changes in immune function were assessed by immune organs index, serum IFN-γ level, gene and protein expressions of immune factors in spleen and bursa of Fabricius. Results from this experiment showed that heat stress enhanced the immune organs' edema by directly increased the organs indexes of spleen and bursa of Fabricius in broilers. Heat stress for 10 d also increased bursa of Fabricius HSP70 protein level and significantly lowered the spleen and bursa of Fabricius proteins expressions of IFN-α, IFN-ß, and IFN-γ in broilers. The IFN-ß and IFN-γ protein levels in spleen and bursa of Fabricius also decreased in heat stressed broilers for 5 d. The gene and protein expressions of TLR4 and TBK1 markedly decreased in spleen and bursa of Fabricius of broilers treated with chronic heat stress. Chai Hu oral liquid reduced edema of immune organs and elevated TLR4-TBK1 signaling pathway to release immune factors. Above results indicated that chronic heat stress induced impaired immune function by inhibiting TLR4-TBK1 signaling pathway, and Chai Hu oral liquid had effective protection of body's immune ability by enhancing this signaling pathway.

[Anti-inflammatory effect, plasma effective components and therapeutic targets of Huanglian Jiedu Decoction on ulcerative colitis mice].

This paper was to investigate the effect of Huanglian Jiedu Decoction(HLJD) on ulcerative colitis(UC) in mice, and determine the effective components in plasma, and virtually screen its therapeutic target, and predict its mechanism. Sixty Balb/c mice were randomly divided into blank group, model group, mesalazine treatment group(0.3 g·kg~(-1)), and HLJD treatment groups(24.66, 12.33, 6.17 g·kg~(-1)). Excepted for the blank group, all the mice in HLJD and mesalazine treatment groups were gavage administration. All mice freely drank 2.5% DSS solution for seven days to induce UC. The disease activity index(DAI) was detected each day. At the end of the experiment, HE staining was used to observe the pathological changes in colon. The content of IL-1ß, IL-6 and TNF-α in colon were determined by ELISA. The effective components in plasma were determined by UPLC-Q-TOF-MS. The reverse docking in PharmMapper was used to screen the component targets. The disease targets of UC were collected by searching TTD, OMIM and GeneCards databases. The intersection of the component targets and disease targets was selected as the therapeutic targets. Then the therapeutic targets were imported into the STRING for GO and KEGG enrichment analysis. Discovery Studio was used to simulate the docking between the components and the targets. RESULTS:: showed that the DAI in the model group increased significantly(P<0.05), and the number of inflammatory cells and infiltration degree increased significantly compared with the blank group. The DAI in HLJD treatment group was significantly reduced(P<0.05), and the number and infiltration degree of inflammatory cells were reduced compared with the model group. The ELISA results showed that the levels of IL-1ß, IL-6 and TNF-α were increased significantly in the model group(P<0.01) compared with the blank group, and significantly down regulated in the HLJD treatment group(P<0.05) compared with the model group. After UPLC-Q-TOF-MS analyse, ten components were identified. The network pharmacology analysis showed that the action targets were significantly enriched in 129 of biological processes, such as response to organic substance, chemical and oxygen-containing compound, etc., as well as 16 of signal pathways, such as IL-17, TNF and hepatitis B signal pathways, were enriched too. The results of molecular docking showed that limonin, palmatine and berberine could bind to CASP3 and MMP9 by hydrogen bond. In conclusion, HLJD could alleviate the colonic mucosal inflammatory infiltration and mucosal damage in UC mice. The mechanism may be related to the anti-inflammatory effect on UC mice by reducing the levels of IL-1ß, IL-6 and TNF-α in colon through limonin, palmatine and berberine regulating IL-17 signal pathway and TNF signal pathway via CASP3 and MMP9 meditated.

Anti-inflammatory effect, plasma effective components and therapeutic targets of Huanglian Jiedu Decoction on ulcerative colitis mice / 中国中药杂志

This paper was to investigate the effect of Huanglian Jiedu Decoction(HLJD) on ulcerative colitis(UC) in mice, and determine the effective components in plasma, and virtually screen its therapeutic target, and predict its mechanism. Sixty Balb/c mice were randomly divided into blank group, model group, mesalazine treatment group(0.3 g·kg~(-1)), and HLJD treatment groups(24.66, 12.33, 6.17 g·kg~(-1)). Excepted for the blank group, all the mice in HLJD and mesalazine treatment groups were gavage administration. All mice freely drank 2.5% DSS solution for seven days to induce UC. The disease activity index(DAI) was detected each day. At the end of the experiment, HE staining was used to observe the pathological changes in colon. The content of IL-1β, IL-6 and TNF-α in colon were determined by ELISA. The effective components in plasma were determined by UPLC-Q-TOF-MS. The reverse docking in PharmMapper was used to screen the component targets. The disease targets of UC were collected by searching TTD, OMIM and GeneCards databases. The intersection of the component targets and disease targets was selected as the therapeutic targets. Then the therapeutic targets were imported into the STRING for GO and KEGG enrichment analysis. Discovery Studio was used to simulate the docking between the components and the targets. RESULTS:: showed that the DAI in the model group increased significantly(P<0.05), and the number of inflammatory cells and infiltration degree increased significantly compared with the blank group. The DAI in HLJD treatment group was significantly reduced(P<0.05), and the number and infiltration degree of inflammatory cells were reduced compared with the model group. The ELISA results showed that the levels of IL-1β, IL-6 and TNF-α were increased significantly in the model group(P<0.01) compared with the blank group, and significantly down regulated in the HLJD treatment group(P<0.05) compared with the model group. After UPLC-Q-TOF-MS analyse, ten components were identified. The network pharmacology analysis showed that the action targets were significantly enriched in 129 of biological processes, such as response to organic substance, chemical and oxygen-containing compound, etc., as well as 16 of signal pathways, such as IL-17, TNF and hepatitis B signal pathways, were enriched too. The results of molecular docking showed that limonin, palmatine and berberine could bind to CASP3 and MMP9 by hydrogen bond. In conclusion, HLJD could alleviate the colonic mucosal inflammatory infiltration and mucosal damage in UC mice. The mechanism may be related to the anti-inflammatory effect on UC mice by reducing the levels of IL-1β, IL-6 and TNF-α in colon through limonin, palmatine and berberine regulating IL-17 signal pathway and TNF signal pathway via CASP3 and MMP9 meditated.

Defense Mechanism of Phosphorothioated DNA under Peroxynitrite-Mediated Oxidative Stress.

DNA phosphorothioation (PT) exists in many pathogenic bacteria; however, the mechanism of PT-DNA resistance to the immune response is unclear. In this work, we meticulously investigated the peroxynitrite (PN) tolerance using PT-bioengineered E. coli strains. The in vivo experiment confirms that the S+ strain survives better than the S- strain under moderately oxidative stress. The LCMS, IC, and GCMS experiments demonstrated that phosphorothioate partially converted to phosphate, and the byproduct included sulfate and elemental sulfur. When O,O-diethyl thiophosphate ester (DETP) was used, the reaction rate k1 was determined to be 4.3 ± 0.5 M-1 s-1 in the first-order for both phosphorothioate and peroxynitrite at 35 °C and pH of 8.0. The IC50 values of phosphorothioate dinucleotides are dramatically increased by 400-700-fold compared to DETP. The SH/OH Yin-Yang mechanism rationalizes the in situ DNA self-defense against PN-mediated oxidative stress at the extra bioenergetic cost of DNA modification.

Genistein-3'-sodium sulphonate protects against lipopolysaccharide-induced lung vascular endothelial cell apoptosis and acute lung injury via BCL-2 signalling.

Under septic conditions, Lipopolysaccharide (LPS)-induced apoptosis of lung vascular endothelial cells (ECs) triggers and aggravates acute lung injury (ALI), which so far has no effective therapeutic options. Genistein-3'-sodium sulphonate (GSS) is a derivative of native soy isoflavone, which has neuro-protective effects through its anti-apoptotic property. However, whether GSS protects against sepsis-induced lung vascular endothelial cell apoptosis and ALI has not been determined. In this study, we found that LPS-induced Myd88/NF-κB/BCL-2 signalling pathway activation and subsequent EC apoptosis were effectively down-regulated by GSS in vitro. Furthermore, GSS not only reversed the sepsis-induced BCL-2 changes in expression in mouse lungs but also blocked sepsis-associated lung vascular barrier disruption and ALI in vivo. Taken together, our results demonstrated that GSS might be a promising candidate for sepsis-induced ALI via its regulating effects on Myd88/NF-κB/BCL-2 signalling in lung ECs.

Immunological modulation effects of an acid Epimedium polysaccharide on immune response in chickens.

The purpose of the present study is to investigate the immunological activities of EPS-1 in the non-specific immune response and specific immune response of chickens. In vitro, the results showed that EPS-1 could increase the proliferation and cytokine secretion (IL-2, IL-4, IFN-γ and TNF-α) of spleen lymphocytes, expression of key surface molecules (MHC II, CD11c, CD40 and CD86) and cytokine secretion (TNF-α and IL-10) of matured chBM-DCs, phagocytic rate of matured chBM-DCs, and enhance the maturation and stimulating capacity of chBM-DCs. In vivo, EPS-1 could also prompt the HI antibody titer, boost the peripheral lymphocyte proliferation, enhance the release of cytokine products in blood (IFN-γ, IL-4 and IL-2) and duodenum (IL-17 and sIgA) of chickens. These results indicated that EPS-1 may have the potential as a powerful immune adjuvant in the treatment of chicken diseases.

Exploration of scientific connotation of Magnoliae Officinalis Cortex after sweating based on network pharmacology / 中草药

Objective: Sweating is one of the important processing methods of traditional Chinese medicine. Some ingredient content of Magnoliae Officinalis Cortex (MOC) is changed after sweating which may cause the difference of efficacy. However, the molecular mechanism of how the changes of ingredient content of MOC affect the efficacy is not clear exactly. Based on the network pharmacology, the relationship between the changes of the ingredient content of MOC and the efficacy after sweating was studied. Methods: The major difference of chemical ingredients before and after sweating were screened out based on the literatures. Swiss Target Prediction was used to predict the potential targets of these components. The high confidence (score 0.900) genes/targets selected out by STRING database were used to construct protein-protein interactions network by using cytoscape 3.6.0. The clusterProfiler package in R was used to analyze gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway. Results: Nine different components (asimilobine, β-eudesmol, honokiol, magnatriol B, magnoflorine, magnolol, magnoloside A, reticuline, and syringin) were screened out. A total of 137 genes/targets were obtained (86 after deduplication). After GO annotation and KEGG enrichment analysis of the network, 550 GO-terms and 30 KEGG pathways were obtained. Conclusion: Through analysis, the change in the pharmacological effects of MOC after sweating is the result of the interaction between the components. The analgesic and anti-gastric ulcer effects of MOC may be mainly produced through the serotonergic synapse, arachidonic acid metabolism and calcium signaling pathway. And the changes in the content of chemical components such as magnolol, honokiol and β-eudesmol are the main reasons for the difference in the efficacy of MOC before and after sweating.

Susceptibility of epithelial tumour cell lines to hyperthermia.

BACKGROUND: Human skin or mucosa exposes cells to both an internal and exogeneous thermal environment and the cells survive within a certain range of temperature. Exogeneous hyperthermia has been applied for the treatment of various types of cancers, fungal disease, and warts. OBJECTIVES: To determine whether different cellular components in the skin adapt to hyperthermic conditions differentially and further elucidate the mechanisms involved. MATERIALS & METHODS: Cell lines derived from normal and tumour epithelial cells were treated with hyperthermic conditions and tested for viability (using an MTS assay), apoptosis (using a FITC-conjugated annexin V apoptosis detection kit), and changes in intracellular calcium (using a calcium-sensitive fluorescent single-wavelength dye, Fluo-4 AM). RESULTS: Thermo-resistance of different cell types was different when cells were subjected to heat at 45̊C for 30 minutes. Stronger effects of hyperthermia were noted on cell viability and apoptosis in epidermal cells relative to their malignant counterparts, except for cell lines harbouring human papillomavirus (HPV). Hyperthermia had a much greater effect on cell viability and apoptosis in a HPV-negative cell line compared to HPV-positive cell lines. We further found that hyperthermia treatment resulted in a strong calcium influx which led to apoptotic cells. However, no obvious increase in apoptosis was observed in cells treated with the CRAC channel selective inhibitor, BTP2, before application of hyperthermia in all cell types, except three cervical cell lines harbouring HPV. CONCLUSION: We propose that hyperthermia results in a CRAC-related strong calcium influx which induces apoptosis, with the exception of HPV-positive cells.