[Role and mechanism of IL-6/STAT3/Th17 signaling pathway in the intervention of forsythia in acute lung injury of septic rats].

Objective: To investigate the mechanism of interleukin-6 (IL-6) /signal transducers and activators of transcriptional 3 (STAT3) /helper T cell 17 (Th17) signaling pathway in lung injury of rats with sepsis intervened by forsythia, with a view to provide experimental basis for the role and mechanism of forsythia in the treatment of sepsis. Methods: In July 2021, 30 healthy Wistar male rats were selected and randomly divided into sham operation group, model group and treatment group, with 10 rats in each group. The rat model of sepsis was established by cecal ligation and puncture. 2 h after recovery, the rats were given traditional Chinese medicine forsythia orally, twice a day at an interval of 12 h. The wet/dry mass ratio (W/D) of lung tissue was detected 24 h after surgery. The morphological changes of lung tissue were detected by HE staining. Flow cytometry was used to detect Th17 population in peripheral blood. The expression levels of IL-6 and interleukin-17A (IL-17A) in serum were determined by enzyme-linked immunosorbent assay. The mRNA expression levels of IL-17A and IL-6 in lung tissues were detected by reverse transcription-polymerase chain reaction. The expression levels of STAT3 and IL-17A in lung tissue were determined by Western blotting. Results: Compared with model group, the W/D of lung tissue in treatment group was decreased, and the difference was statistically significant (P<0.05). HE staining of lung tissue showed that compared with the model group, the degree of lung lesion and injury was reduced in the treatment group. Compared with sham operation group, the proportion of Th17 cells in CD4 lymphocytes in peripheral blood of rats in model group was significantly increased (P<0.05). Compared with model group, the proportion of Th17 cells in CD4 lymphocytes in peripheral blood of rats in treatment group was significantly decreased (P<0.05). Compared with sham operation group, peripheral blood serum IL-6 and IL-17 of rats in model group were significantly increased (P<0.05). Compared with model group, IL-6 and IL-17 in peripheral blood serum of rats in treatment group were decreased (P<0.05). Compared with sham operation group, the expressions of IL-17A and IL-6 mRNA in lung tissue of model group were significantly increased (P<0.05). Compared with model group, the expressions of IL-17A and IL-6 mRNA in lung tissue of rats in treatment group were significantly decreased (P<0.05). Compared with sham operation group, the protein expressions of STAT3 and IL-17A in lung tissue in model group were significantly increased (P<0.05). Compared with model group, the pritein expressions of STAT3 and IL-17A in lung tissue in treatment group were significantly decreased (P<0.05) . Conclusion: Forsythia plays a role in alleviating lung injury by down-regulating the expressions of the signaling pathway IL-6/STAT3/Th17, which providing a new target for the treatment of sepsis induced lung injury.

Pharmacological activity and clinical progress of Triptolide and its derivatives LLDT-8, PG490-88Na, and Minnelide: a narrative review.

Triptolide, a compound isolated from a Chinese medicinal herb, has potent antitumor, immunosuppressive, and anti-inflammatory properties. Due to its interesting structural features and diverse pharmacological activities, it has attracted great interest by the Society of Organic Chemistry and Pharmaceutical Chemistry. However, its clinical potential is greatly hampered by limited aqueous solubility and oral bioavailability, and multi-organ toxicity. In recent years, various derivatives of Triptolide have made varying degrees of progress in the treatment of inflammatory diseases, autoimmune diseases, and cancer. The most researched and potentially clinically valuable of them were (5R)-5-hydroxytriptolide (LLDT-8), PG490-88Na (F6008), and Minnelide. In this review, we provide an overview of the advancements made in triptolide and several of its derivatives' biological activity, mechanisms of action, and clinical development. We also summarized some prospects for the future development of triptolide and its derivatives. It is hoped to contribute to a better understanding of the progress in this field, make constructive suggestions for further studies of Triptolide, and provide a theoretical reference for the rational development of new drugs.

The earliest human occupation of the high-altitude Tibetan Plateau 40 thousand to 30 thousand years ago.

The Tibetan Plateau is the highest and one of the most demanding environments ever inhabited by humans. We investigated the timing and mechanisms of its initial colonization at the Nwya Devu site, located nearly 4600 meters above sea level. This site, dating from 40,000 to 30,000 years ago, is the highest Paleolithic archaeological site yet identified globally. Nwya Devu has yielded an abundant blade tool assemblage, indicating hitherto-unknown capacities for the survival of modern humans who camped in this environment. This site deepens the history of the peopling of the "roof of the world" and the antiquity of human high-altitude occupations more generally.

Association of fish and long-chain omega-3 fatty acids intakes with total and cause-specific mortality: prospective analysis of 421 309 individuals.

BACKGROUND: Prevailing dietary guidelines recommend regular fish consumption. However, the associations of fish and long-chain omega-3 polyunsaturated fatty acids (LCn-3 PUFAs) intakes with mortality remain unclear. OBJECTIVES: To examine the associations of fish and LCn-3 PUFAs intakes with total and cause-specific mortality. METHODS: A total of 240 729 men and 180 580 women from NIH-AARP Diet and Health Study were prospectively followed-up for 16 years. Dietary intakes were assessed using a validated NIH Diet History Questionnaire. RESULTS: A total of 54 230 men and 30 882 women died during 6.07 million person-years of follow-up. Higher fish and LCn-3 PUFAs intakes were significantly associated with lower total mortality (P < 0.0001). Comparing the highest with lowest quintiles of fish intake, men had 9% (95% confidence interval, 6-11%) lower total mortality, 10% (6-15%) lower cardiovascular disease (CVD) mortality, 6% (1-10%) lower cancer mortality, 20% (11-28%) lower respiratory disease mortality and 37% (17-53%) lower chronic liver disease mortality, while women had 8% (5-12%) lower total mortality, 10% (3-17%) lower CVD mortality and 38% (20-52%) lower Alzheimer's disease mortality. Fried fish consumption was not related to mortality in men whereas positively associated with mortality from all causes (P = 0.011), CVD and respiratory disease in women. LCn-3 PUFAs intake was associated with 15% and 18% lower CVD mortality in men and women across extreme quintiles, respectively. CONCLUSION: Consumption of fish and LCn-3 PUFAs was robustly associated with lower mortality from major causes. Our findings support current guidelines for fish consumption while advice on non-frying preparation methods is needed.

Krüppel-like factor 4 acts as a potential therapeutic target of Sijunzi decoction for treatment of colorectal cancer.

Sijunzi decoction (SJZD) is a traditional Chinese medicine prescription for the prevention and treatment of colorectal cancer. Our study is aimed to identify the potential therapeutic target of SJZD. Microarray analysis was performed on the patients with colorectal cancer under treatment of SJZD. The mRNA targets of SJZD were predicted by BATMAN-TCM database and were further identified by integrated analysis of expression data from TCGA. The correlation of gene expression and clinical characteristics was analyzed. Microarray analysis indicated that Krüppel-like factor 4 (KLF4) was significantly upregulated after intervention of SJZD. BATMAN-TCM prediction showed that KLF4 was an mRNA target of SJZD and it was downregulated in colorectal cancer by integrated analysis of expression data from TCGA. KLF4 may act as an administered indicator to assess whether adjuvant postoperative pharmaceutical therapy is needed for patients with colorectal cancer. Low KLF4 expression was significantly correlated with reductions of overall survival and recurrence rate. Our results suggested that KLF4 may be the potential therapeutic target of SJZD for the treatment of colorectal cancer.

Tea Polyphenol inhibits autophagy to sensitize Epirubicin-induced apoptosis in human bladder cancer cells.

Resistance to anticancer agents such as Epirubicin (EPI) becomes a great challenge for treating bladder cancer. However, the mechanism by which chemoresistance arised is still elusive. In the present study, we showed evidence that EPI induced cytoprotective autophagy in bladder cancer cell lines T24 and BIU87. In addition, EPI robustly activated JNK-mediated phosphorylation of Bcl-2 and disruption of Bcl-2/Beclin-1 complex. Furthermore, the green tea derivative tea polyphenol (TP) inhibited EPI-induced autophagy and promoted apoptosis induced by EPI in bladder cancer cells. These results revealed a pathway for EPI-induced autophagy that involved in JNK/Bcl-2/Beclin-1 in bladder cancer cells, and that TP synergistically promoted EPI-induced apoptosis at least partly through autophagy inhibition. Thus, TP could be utilized in combination with EPI to improve EPI-based bladder cancer therapy.

Effect of dietary supplementation of Ligustrum lucidum on performance, egg quality and blood biochemical parameters of Hy-Line Brown hens during the late laying period.

The fruit of Ligustrum lucidum (FLL, Nuzhenzi in Chinese) is an important traditional medicine, and have attracted significant research attention because of their various biological activities. However, there are few research reports available on the use of FLL as a feed additive in livestock nutrition, particularly in layers. This study was conducted to determine the effects of supplementation of the diet of laying hens with FLL on laying performance, egg quality and blood metabolites. A total of 360 72-week-old hens were allocated to three dietary treatments (eight replications of 15 hens/treatment group) and were fed either a control diet or a diet supplemented with an inclusion level of 0.25% or 0.50% of FLL powder in the final feed, until 78 weeks of age. Hens were housed in a three-tier cage system. Feed and water were provided ad libitum. Blood samples and eggs were collected at the end of the experiment. The results showed that dietary supplementation with FLL did not affect egg weight, feed conversion ratio, eggshell thickness, albumen height, egg yolk color, eggshell breaking strength or egg shape index. However, FLL supplementation significantly decreased (P<0.001) mortality, cracked-egg rate and blood serum levels of cholesterol, low-density lipoprotein cholesterol, triglycerides and alanine aminotransferase, and increased (P<0.001) blood serum levels of high-density lipoprotein cholesterol. No differences in serum levels of total protein, albumin, glucose, calcium, aspartate aminotransferase or alkaline phosphatase were observed in hens fed FLL compared with the control group. It can be concluded that FLL, at a supplementation level of 0.25% final feed, can be used as an effective feed additive to improve the performance of laying hens during the late laying period.

Effects of Chinese herbal mixture on performance, egg quality and blood biochemical parameters of laying hens.

The aim of the study was to evaluate the effect of Chinese herbal mixture (CHM) in laying hen diets on performance, egg quality and egg nutrition components, as well as selected blood biochemical parameters. A total of 270 Lohmann Brown laying hens, 24 week of age, were randomly distributed into three dietary treatments and fed for 6 week. The CHM was used at the levels of 0%, 0.5% and 1.0% in the diets of the control and two treatment groups respectively. Each dietary treatment was divided into five replicates, comprising of 18 hens each. Hens were housed in a 3-tier battery system. Feed and water were provided ad libitum. Blood samples and eggs were collected at the end of the experiment. The results showed that dietary treatments did not affect egg weight, mortality, eggshell thickness, albumen height, Haugh units, eggshell-breaking strength and egg-shape index. Dietary supplementation of CHM significantly improved (p < 0.05) laying rate and the lowest feed conversion ratio were observed with 1.0% CHM supplementation diets. CHM supplementation decreased (p < 0.05) cracked-egg rate, egg yolk cholesterol, blood serum levels of cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C) and alanine aminotransferase (ALT) and increased blood serum levels of high-density lipoprotein cholesterol (HDL-C). No differences in serum total protein, serum albumen, serum glucose and aspartate amino transferase (AST) were observed in hens fed CHM. In conclusion, dietary supplementation with CHM improved egg production and egg quality and reduced serum cholesterol concentrations in laying hens. Dietary supplementation of 1.0% CHM in layer diets may be a feasible means of producing eggs with lower cholesterol and higher egg yolk phospholipid contents for health conscious consumers.

Gastrodin suppresses BACE1 expression under oxidative stress condition via inhibition of the PKR/eIF2α pathway in Alzheimer's disease.

The expression of ß-site APP-cleaving enzyme 1 (BACE1) is increased in the brain of late-onset sporadic Alzheimer's disease (AD) and oxidative stress may be the potential cause of this event. The phenolic glucoside gastrodin (Gas), a main component of a Chinese herbal medicine Gastrodia elata Blume, has been demonstrated to display antioxidant activity and suppresses BACE1 expression. However, the mechanisms by which Gas suppresses BACE1 expression are not clear. Morris water maze test was performed to assess the effect of Gas treatment on memory impairments in Tg2576 mice. The level of oxidative stress in the brain of Tg2576 mice was determined by measuring the superoxide dismutase (SOD) activity, catalase (CAT) activity, and the levels of malondialdehyde (MDA) and ROS. In vivo and in vitro, we detected the expression levels of BACE1, pPKRThr446, PKR, pPERKThr981, PERK, peIF2αSer51, and eIF2α using western blot analysis. We found that Gas improved learning and memory abilities of Tg2576 transgenic mice and attenuated intracellular oxidative stress in hippocampi of Tg2576 mice. We discovered that the expression levels of BACE1, activated PKR (pPKRThr446) and activated eIF2α (peIF2αSer51) were elevated in the brains of Tg2576 mice and hydrogen peroxide (H2O2)-stimulated SH-SY5Y cells. Moreover, peptide PKR inhibitor (PRI) and Gas down-regulated BACE1 expression in Tg2576 mice and H2O2-stimulated SH-SY5Y cells by inhibiting activation of PKR and eIF2α. Gas alleviates memory deficits in mice and suppresses BACE1 expression by inhibiting the protein kinase/Eukaryotic initiation factor-2α (PKR/eIF2α) pathway. The research suggested that Gas may develop as an drug candidate in neurodegenerative diseases.

Characterization of complementary determinant region 3δ in human MutS homologue 2-specific γδ T cells.

γδT cells function as sentinels in early host responses to infections and malignancies. Previously, we found ectopically expressed human MutS homologue 2 (hMSH2), recognized by γδT cells, triggered a γδT cell-mediated cytolysis to tumor cells. However, the characteristics of hMSH2-specific γδ Τ cells are not fully understood. In this study, we investigated the complementary determinant region (CDR) 3δ diversity of hMSH2-specific γδ T cells. We found that the CDR3δ sequences of hMSH2-specific γδ T cells displayed limited diversity, while the length and germline gene usage showed no differences compared with whole CDR3δ immune repertoire. There are more hydrophilic amino acids in P/N insert of hMSH2-specific γδ T cells including the more conserved amino acid at the position 97. Our results offer clues to understanding antigen recognition pattern of γδ T cells to stress-induced hMSH2 of tumor cells and also the mechanism of γδT cell-mediated tumor immune surveillance.

Efficacy of low-level laser therapy for accelerating tooth movement during orthodontic treatment: a systematic review and meta-analysis.

This review aimed to evaluate the efficacy of low-level laser therapy (LLLT) for accelerating tooth movement during orthodontic treatment. An extensive electronic search was conducted by two reviewers. Randomized controlled trials (RCTs) and quasi-RCTs concerning the efficacy of LLLT for accelerating tooth movement during orthodontic treatment were searched in CENTRAL, Medline, PubMed, Embase, China Biology Medicine Disc (CBM), China National Knowledge Infrastructure (CNKI), and Google Scholar. Six RCTs and three quasi-RCTs, involving 211 patients from six countries, were selected from 173 relevant studies. All nine articles were feasible for the systematic review and meta-analysis, five of which were assessed as moderate risk of bias, while the rest were assessed as high risk of bias. The mean difference and the 95 % confidence interval (95 % CI) of accumulative moved distance of teeth were observed among all the researches. The results showed that the LLLT could accelerate orthodontic tooth movement (OTM) in 7 days (mean difference 0.19, 95 % CI [0.02, 0.37], p = 0.03) and 2 months (mean difference 1.08, 95 % CI [0.16, 2.01], p = 0.02). Moreover, a relatively lower energy density (5 and 8 J/cm(2)) was seemingly more effective than 20 and 25 J/cm(2) and even higher ones.

A systematic review and meta-analysis on the efficacy of low-level laser therapy in the management of complication after mandibular third molar surgery.

The successful reduction of postoperative discomfort is of great significance. This review aims to evaluate the efficacy of low-level laser therapy (LLLT) for the reduction of complication caused by impacted mandibular third molars extraction. An extensive literature search up to October 2013 for randomized controlled trials (RCTs) was performed through CENTRAL, PubMed, Embase, Medline, and CNKI. Six RCTs in which involves 193 participants are included in the meta-analysis. Among them, three RCTs exhibit a moderate risk of bias, while the other three show a high bias risk. Compared with placebo laser/control group, pain is significantly reduced with LLLT on the first day (mean difference [MD] = -2.63, 95% confidence interval [CI] -4.46 to -0.79, P = 0.005). The superiority of LLLT in pain control persists on the second day (MD = -2.34, 95% CI -4.61 to -0.06, P = 0.04) and the third day (MD = -3.40, 95% CI -4.12 to -2.68, P < 0.00001). Moreover, LLLT reduces an average of 4.94 mm (MD = 4.94, 95 % CI 1.53 to 8.34, P = 0.004) of trismus compared with placebo laser irradiation in the first 3 days. On the seventh day, the superiority of LLLT also persists (MD = 3.24, 95% CI 0.37 to 6.12, P = 0.03). In the first 3 days after surgery, extraoral irradiation (MD = -0.69, 95% CI -1.30 to -0.08, P = 0.03) and intraoral combined with extraoral irradiation (MD = -0.65, 95% CI -1.15 to -0.15, P = 0.01) reduced facial swelling significantly. On the seventh day, the intraoral combined with extraoral irradiation group (MD = -0.32, 95% CI -0.59 to -0.06, P = 0.02) still showed benefit in relieving facial swelling. However, because of the heterogeneity of intervention and outcomes assessment and risk of bias of included trials, the efficacy is proved with limited evidence. In the future, well-designed RCTs with larger sample size will be required to provide clearer recommendations.

Paeoniflorin inhibited the tumor invasion and metastasis in human hepatocellular carcinoma cells.

OBJECTIVE: Evidence suggests that paeoniflorin may be involved in anticancer activities. Here, we have investigated the effects of paeoniflorin and correlative mechanisms on anti-invasion and anti-metastasis in human hepatocellular carcinoma (HCC) cell lines. MATERIALS AND METHODS: In the current study, we have applied 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay to determine the proliferative effect of HepG2 and Bel-7402, two human hepatoma cell lines, and we have established a boyden chamber assay, a wound healing assay and cell adhesion assay to detect and quantify the invasion, metastasis and adhesion of both HepG2 and Bel-7402. In addition, we have analyzed the protein expression of matrix metalloproteinas (MMP)-9, E-cadherin (E-cad) and extracellular signal-regulated kinase (ERK) in both cell lines through western blot analysis. RESULTS: Paeoniflorin (6. 25-200 µM) had inhibitory effect on the growth of HepG2 and Bel-7402 cell lines, and reduced significantly invasion, metastasis and adhesion of HCC cell lines. In addition, paeoniflorin decreased the expression of MMP-9 and ERK in HepG2 and Bel-7402 cells, and increased expression of E-cad in both cell lines. CONCLUSIONS: Paeoniflorin is effective anti-metastatic and anti-invasive agent for suppressing HCC invasion and metastasis (Fig. 5, Ref. 30).

Efficacy of low-level laser therapy in the management of orthodontic pain: a systematic review and meta-analysis.

This review aimed to identify the efficacy of low-level laser therapy (LLLT) in the management of orthodontic pain. This systematic review and meta-analysis was carried out in accordance with Cochrane Handbook and the PRISMA statement. An extensive literature search for RCTs, quasi-RCTs, and CCTs was performed through CENTRAL, PubMed, Embase, Medline, CNKI, and CBM up to October 2011. Risk of bias assessment was performed via referring to the Cochrane tool for risk of bias assessment. Meta-analysis was implemented using Review Manager 5.1. As a result, four RCTs, two quasi-RCTs, and two CCTs were selected from 152 relevant studies, including 641 patients from six countries. The meta-analysis demonstrated that 24% risk of incidence of pain was reduced by LLLT (RR = 0.76, 95% CI range 0.63-0.92, P = 0.006). In addition, compared to the control group, LLLT brought forward "the most painful day" (MD = -0.42, 95% CI range -0.74- -0.10, P = 0.009). Furthermore, the LLLT group also implied a trend of earlier end of pain compared with the control group (MD = -1.37, 95% CI range -3.37-0.64, P = 0.18) and the pseudo-laser group (MD = -1.04, 95% CI range -4.22-2.15, P = 0.52). However, because of the methodological shortcomings and risk of bias of included trials, LLLT was proved with limited evidence in delaying pain onset and reducing pain intensity. In the future, larger and better-designed RCTs will be required to provide clearer recommendations.

Yin Yang 1 positively regulates BRCA1 and inhibits mammary cancer formation.

Expression of the breast cancer-associated gene 1 (BRCA1) in sporadic breast cancers is usually reduced, yet the underlying mechanisms remains elusive. To identify factors that are responsible for reduced BRCA1 expression, we screened 92 known transcription factors for their ability to regulate expression of BRCA1. Among several potential regulators, the Gli-Krueppel-related transcription factor Yin Yang 1 (YY1) showed the most dramatic transactivation of the BRCA1 promoter. YY1 binds to the promoter of BRCA1, and its overexpression resulted in increased expression of BRCA1 and a number of BRCA1 downstream genes. We further showed that overexpression of YY1 in cancer cells inhibited cell proliferation, foci formation and tumor growth in nude mice. To assess the clinical relevance between YY1 and BRCA1, we studied expression of YY1 and BRCA1 from human breast cancer samples and tissue arrays, and detected a significant positive correlation between the level of YY1 and BRCA1 expression in these cancers. Taken together, these findings suggest that YY1 is a key regulator of BRCA1 expression and may be causally linked to the molecular etiology of human breast cancer.

A rare complication of ear piercing: a case of subcutaneous phaeohyphomycosis caused by Veronaea botryosa in China.

We present the third case of phaeohyphomycosis caused by Veronaea botryosa in China and the tenth case worldwide. A 16-year-old Chinese girl developed crusted, verrucous lesions, initially on the left ear and later on the left buttock, within 2-5 months of receiving an ear piercing. Histopathological examination of biopsy specimens confirmed diagnosis of subcutaneous phaeohyphomycosis. Microscopic examination of the colonies recovered in culture from a portion of the biopsy specimen resulted in the identification of Veronaea botryosa based primarily on the presence of two-celled, brownish pigmented, cylindrical conidia produced sympodially from erect conidiogenous cells. The lesions significantly improved with daily oral treatment with itraconazole 400 mg and adjuvant thermotherapy for 6 months. A maintenance therapy with low dose itraconazole was prescribed in order to achieve clinical and mycological cure. A two-year follow-up didn't reveal any recurrence of infection. Our case is the first report of V. botryosa infection associated with a cosmetic procedure, which suggests that skin piercing could precipitate V. botryosa or other dematiaceous, as well as opportunistic fungal infections.

Cutaneous stimulation improves function of a chronic patient with cerebellar damage.

The prognosis of cerebellar hemorrhage with brain stem compression is known to be poor, and patients who can usually survive are severely disabled with limited benefit from conventional rehabilitation. An innovative cutaneous stimulation was administered to a chronic patient (2 years after the incidence) who has severe ataxia, gait imbalance and limb spasticity caused by cerebellar hemorrhage. After 8 months of intervention, patient's function as evaluated by two functional measures has improved by 40%. In addition, the patient's ataxia and hypotonia have improved significantly in which he has regained the abilities to grasp objects, sit upright, control his equilibrium, and monitor an electric wheelchair. The present case study demonstrated a significant improvement of a chronic severely disabled patient who received the intervention 2 years after the accident, suggesting that the cutaneous stimulation may be a possible effective neurologic intervention.

Study of the distribution of non-point source pollution in the watershed of the Miyun Reservoir, Beijing, China.

Nitrogen and phosphorus are major nutrients to cause eutrophication to degrade the water quality of the Miyun Reservoir, a very important drinking water source of Beijing in China. These are mainly from non-point sources. The watershed in Miyun County is selected as the study region with a total area of 1400 km2. Four typical monitoring catchments and two experimental units were used to monitor the precipitation, runoff, sediment yield and pollutant loading related to various land uses in the meantime. The results show that the total nutrient loss amount of TN and TP is 898.07 t/a, and 40.70 t/a, respectively, in which nutrient N and P carried by runoff is 91.3% and 77.3%, respectively. There is relatively heavier soil erosion at the northern mountain area whereas the main nutrient loss occurs near the northeast rim of the reservoir. Different land uses influence the loss of non-point source pollutants. The amount of nutrient loss from agricultural land per unit is the highest, nutrient loss from forestry is the second highest and that from grassland is the lowest. However, due to the variability of land use areas, agricultural land contributes the greatest amount of TP and forestry lands the greatest amount of TN.