Gut microbiota dynamics and fecal SCFAs after colonoscopy: accelerating microbiome stabilization by Clostridium butyricum.

BACKGROUND: Colonoscopy is a classic diagnostic method with possible complications including abdominal pain and diarrhoea. In this study, gut microbiota dynamics and related metabolic products during and after colonoscopy were explored to accelerate gut microbiome balance through probiotics. METHODS: The gut microbiota and fecal short-chain fatty acids (SCFAs) were analyzed in four healthy subjects before and after colonoscopy, along with seven individuals supplemented with Clostridium butyricum. We employed 16S rRNA sequencing and GC-MS to investigate these changes. We also conducted bioinformatic analysis to explore the buk gene, encoding butyrate kinase, across C. butyricum strains from the human gut. RESULTS: The gut microbiota and fecal short-chain fatty acids (SCFAs) of four healthy subjects were recovered on the 7th day after colonoscopy. We found that Clostridium and other bacteria might have efficient butyric acid production through bioinformatic analysis of the buk and assessment of the transcriptional level of the buk. Supplementation of seven healthy subjects with Clostridium butyricum after colonoscopy resulted in a quicker recovery and stabilization of gut microbiota and fecal SCFAs on the third day. CONCLUSION: We suggest that supplementation of Clostridium butyricum after colonoscopy should be considered in future routine clinical practice.

Protective effects of functional Nano-Selenium supplementation on spleen injury through regulation of p38 MAPK and NF-κB protein expression.

Selenium (Se) is a trace element necessary for humans to maintain normal physiological activities, and Se deficiency may lead to splenic injury, while Se supplementation can alleviate splenic injury. However, the mechanism is unclear. In this study, we constructed a Se deficiency animal model by feeding Sprague-Dawley (SD) rats with low Se feed. Meanwhile, we observed the repairing effect of Se supplementation on splenic injury with two doses of novel nano-selenium (Nano-Se) supplement by gavage. We measured the Se content in the spleens of the rats by atomic fluorescence spectroscopy (AFS) method and combined the results of hematoxylin-eosin (HE) and Masson staining to observe the splenic injury, comprehensively evaluating the construction of the animal model of low selenium-induced splenic injury. We measured the mRNA and protein expression levels of p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor kappa-B (NF-κB), and interleukin-6 (IL-6) in the spleen by Real-time quantitative polymerase chain reaction (qPCR), western blot (WB), and immunohistochemistry (IHC). We found that the Se deficiency group exhibited lower Se content, splenic fibrosis, and high expression of p38 MAPK, NF-κB, and IL-6 compared to the normal group. The Se supplement groups exhibited higher Se content, attenuated splenic injury, and down-regulated expression of p38 MAPK, NF-κB, and IL-6 relative to the Se deficiency group. This study suggests that Se deficiency leads to splenic injury in rats, and Se supplementation may attenuate splenic injury by inhibiting the expression of p38 MAPK, NF-κB and IL-6.

Mechanisms by which sheep milk consumption ameliorates insulin resistance in high-fat diet-fed mice.

Sheep milk is rich in fat, protein, vitamins and minerals and is also one of the most important sources of natural bioactives. Several biopeptides in sheep milk have been reported to possess antibacterial, antiviral and anti-inflammatory properties, and they may prevent type 2 diabetes (T2D), disease and cancer. However, the precise mechanism(s) underlying the protective role of sheep milk against T2D development remains unclear. Therefore, in the current study, we investigated the effect of sheep milk on insulin resistance and glucose intolerance in high-fat diet (HFD)-fed mice, by conducting intraperitoneal glucose tolerance tests, metabolic cage studies, genomic sequencing, polymerase chain reaction, and biochemical assays. Hyperinsulinemic-euglycemic clamp-based experiments revealed that mice consuming sheep milk exhibited lower hepatic glucose production than mice in the control group. These findings further elucidate the mechanism by which dietary supplementation with sheep milk alleviates HFD-induced systemic glucose intolerance.

Time points of outcome are often neglected in acupuncture meta-analyses: a methodological survey.

OBJECTIVES: To systematically understand the transparency of outcome measurement time point reporting in meta-analyses of acupuncture. STUDY DESIGN AND SETTING: We searched for meta-analyses of acupuncture published between 2013 and 2022 in PubMed, Embase, and Cochrane Library. A team of method-trained investigators screened studies for eligibility and collected data using pilot-tested standardized questionnaires. We documented in detail the reporting of outcome measurement time points in acupuncture meta-analyses. RESULTS: A total of 224 acupuncture meta-analyses were included. Of these, 98 (43.8%) studies did not specify the time points of primary outcome. Among 126 (56.3%) meta-analyses which reported the time points of primary outcome, only 22 (17.5%) meta-analyses specified time points in corresponding protocol. Among 48 (38.1%) meta-analyses that estimated treatment effects of multiple time points, 11 (22.9%) meta-analyses used inappropriate meta-analysis method (subgroup analysis) to pool effect size, and none of the meta-analyses used advanced methods for pooling effect sizes at different time points. CONCLUSION: Transparency in reporting outcome time points for acupuncture meta-analyses and appropriate methods to pool the effect size of multiple time points were lacking. For future systematic reviews, the transparency of outcome measurement time points should be emphasized in the protocols and final reports. Furthermore, advanced methods should be considered for pooling effect sizes at multiple time points.

The dynamic landscape of chromatin accessibility and active regulatory elements in the mediobasal hypothalamus influences the seasonal activation of the reproductive axis in the male quail under long light exposure.

BACKGROUND: In cold and temperate zones, seasonal reproduction plays a crucial role in the survival and reproductive success of species. The photoperiod influences reproductive processes in seasonal breeders through the hypothalamic-pituitary-gonadal (HPG) axis, in which the mediobasal hypothalamus (MBH) serves as the central region responsible for transmitting light information to the endocrine system. However, the cis-regulatory elements and the transcriptional activation mechanisms related to seasonal activation of the reproductive axis in MBH remain largely unclear. In this study, an artificial photoperiod program was used to induce the HPG axis activation in male quails, and we compared changes in chromatin accessibility changes during the seasonal activation of the HPG axis. RESULTS: Alterations in chromatin accessibility occurred in the mediobasal hypothalamus (MBH) and stabilized at LD7 during the activation of the HPG axis. Most open chromatin regions (OCRs) are enriched mainly in introns and distal intergenic regions. The differentially accessible regions (DARs) showed enrichment of binding motifs of the RFX, NKX, and MEF family of transcription factors that gained-loss accessibility under long-day conditions, while the binding motifs of the nuclear receptor (NR) superfamily and BZIP family gained-open accessibility. Retinoic acid signaling and GTPase-mediated signal transduction are involved in adaptation to long days and maintenance of the HPG axis activation. According to our footprint analysis, three clock-output genes (TEF, DBP, and HLF) and the THRA were the first responders to long days in LD3. THRB, NR3C2, AR, and NR3C1 are the key players associated with the initiation and maintenance of the activation of the HPG axis, which appeared at LD7 and tended to be stable under long-day conditions. By integrating chromatin and the transcriptome, three genes (DIO2, SLC16A2, and PDE6H) involved in thyroid hormone signaling showed differential chromatin accessibility and expression levels during the seasonal activation of the HPG axis. TRPA1, a target of THRB identified by DAP-seq, was sensitive to photoactivation and exhibited differential expression levels between short- and long-day conditions. CONCLUSION: Our data suggest that trans effects were the main factors affecting gene expression during the seasonal activation of the HPG axis. This study could lead to further research on the seasonal reproductive behavior of birds, particularly the role of MBH in controlling seasonal reproductive behavior.

The Impact of Various Organic Phosphorus Carriers on the Uptake and Use Efficiency in Barley.

Organic phosphorus (OP) is an essential component of the soil P cycle, which contributes to barley nutrition after its mineralization into inorganic phosphorus (Pi). However, the dynamics of OP utilization in the barley rhizosphere remain unclear. In this study, phytin was screened out from six OP carriers, which could reflect the difference in OP utilization between a P-inefficient genotype Baudin and a P-efficient genotype CN4027. The phosphorus utilization efficiency (PUE), root morphological traits, and expression of genes associated with P utilization were assessed under P deficiency or phytin treatments. P deficiency resulted in a greater root surface area and thicker roots. In barley fed with phytin as a P carrier, the APase activities of CN4027 were 2-3-fold lower than those of Baudin, while the phytase activities of CN4027 were 2-3-fold higher than those of Baudin. The PUE in CN4027 was mainly enhanced by activating phytase to improve the root absorption and utilization of Pi resulting from OP mineralization, while the PUE in Baudin was mainly enhanced by activating APase to improve the shoot reuse capacity. A phosphate transporter gene HvPHT1;8 regulated P transport from the roots to the shoots, while a purple acid phosphatase (PAP) family gene HvPAPhy_b contributed to the reuse of P in barley.

Secoiridoid glycosides from the fruits of Ligustrum lucidum and their in vitro anti-inflammatory activity.

Seven new secoiridoid glycosides (1-7), together with a known analogue (8), were isolated from the fruits of Ligustrum lucidum. Their structures with absolute configurations were determined by HR-ESI-MS, 1D and 2D NMR, and electronic circular dichroism (ECD) spectroscopic analysis, as well as biogenetic consideration. Compounds 1 and 2 are the first examples of secoiridoid glycoside dimers featuring a rare rearranged oleoside-type secoiridoid moiety, and compounds 3-7 represent a new class of oleoside-type secoiridoid glycosides with unusual stereochemistry at C-1 position. A plausible biosynthetic pathway for this group of unusual secoiridoid glycosides was also proposed herein. In addition, the isolates were evaluated for their in vitro anti-inflammatory activity, and all tested compounds exhibited modest inhibitory effects against nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 macrophages.

Single and Combined Effects of Short-Term Selenium Deficiency and T-2 Toxin-Induced Kidney Pathological Injury Through the MMPs/TIMPs System.

The single and combined effects of short-term selenium (Se) deficiency and T-2 toxin-induced kidney pathological injury through the MMPs/TIMPs system were investigated. Forty-eight rats were randomly divided into control, 10 ng/g T-2 toxin, 100 ng/g T-2 toxin, Se-deficient, 10 ng/g T-2 toxin and Se deficiency combined, and 100 ng/g T-2 toxin and Se deficiency combined groups for a 4-week intervention. The kidney Se concentration was measured to evaluate the construction of animal models of Se deficiency. Kidney tissues were analyzed by hematoxylin-eosin staining, Masson staining, and transmission electron microscope to observe the pathological changes, the severity of kidney fibrosis, and ultrastructural changes, respectively. Meanwhile, quantitative polymerase chain reaction and immunohistochemical staining were used to analyze the gene and protein expression levels of matrix metallopeptidase 2/3 (MMP2/3) and tissue inhibitor of metalloproteinase 1 (TIMP1). The results showed that short-term Se deficiency and T-2 toxin exposure can cause kidney injury through tubular degeneration and even lead to kidney fibrosis. And the combination of T-2 toxin and Se deficiency had a synergistic effect on the kidney. A dose-response effect of the T-2 toxin was also observed. At the gene and protein levels, the expression of MMP2/3 in the intervention group increased, while the expression of TIMP1 decreased compared with the control group. In conclusion, short-term Se deficiency and T-2 toxin exposure might lead to injury and even the development of fibrosis in the kidneys, and combined intervention can increase the severity with a dose-dependent trend. MMP2/3 and TIMP1 likely play a significant role in the development of kidney fibrosis.

Short-term Dietary Selenium Deficiency Induced Liver Fibrosis by Inhibiting the Akt/mTOR Signaling Pathway in Rats.

The effects of short-term dietary selenium deficiency on the liver and protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway were evaluated. Fourteen growing rats were randomly divided into control and selenium deficiency groups and fed standard and selenium-deficient diets for 4 weeks, respectively. The serum and liver selenium concentrations were measured to evaluate the construction of animal models with selenium deficiency. Liver tissues were analyzed by transmission electron microscope, hematoxylin-eosin staining, and Masson staining to observe the ultrastructural changes, pathological changes, and severity of liver fibrosis, respectively. Besides, immunohistochemical staining (IHC) was used to analyze the effects of selenium deficiency on the expression of key proteins in the Akt/mTOR signaling pathway. The results showed that selenium concentrations in the serum and liver tissue were significantly lower in the selenium deficiency group than in the control group, and the selenium deficiency intervention could affect the morphology and structure of hepatocytes and mitochondria. Meanwhile, the liver tissue showed structural damage and fibrotic changes in the selenium deficiency group. The IHC results showed the positive staining rates of Akt, phosphorylation-modified protein kinase B (p-Akt), mTOR, and phosphorylation-modified mammalian target of the rapamycin (p-mTOR) in the liver of the selenium deficiency group which were significantly lower than that of the control group. In conclusion, short-term selenium deficiency dietary intervention could lead to liver fibrosis by inhibiting the Akt/mTOR signaling pathway.

A novel method for quality consistency evaluation of Glycyrrhiza formula granules based on a spectrum-effect study.

Quality consistency of Glycyrrhiza formula granules is essential for guaranteeing clinical efficacy. However, a suitable method to accurately and conveniently evaluate the consistency of the clinical efficacy of Glycyrrhiza formula granules is currently not available. This study established a method for the simultaneous determination of 12 active components in Glycyrrhiza formula granules using ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry. The rate of inhibition of cyclooxygenase-2 by different batches of Glycyrrhiza formula granules was determined. Near-infrared spectra were collected for different batches of Glycyrrhiza formula granules to detect their biological activity in the inhibition of cyclooxygenase-2. The quality consistency of the 11 batches of Glycyrrhiza formula granules was evaluated using principal component and correlation analyses. The results showed significant differences in the formula granules of Glycyrrhiza uralensis produced by the different manufacturers. Some differences were also observed among batches of formula granules produced by the same manufacturer. Correlation analysis of the chemical components and cyclooxygenase-2 activity showed that glycyrrhizic acid, liquiritin, and isoliquiritin were the main active components of Glycyrrhiza. Correlation analysis of the near-infrared spectra and cyclooxygenase-2 inhibition activity showed a high correlation between the active components and three characteristic bands: 3383-3995, 4227-4651, and 5315-5878 cm-1 . In this study, the main active anti-inflammatory components of Glycyrrhiza granules were screened. Thus, the near-infrared spectrum and characteristic active band of multi-index active components can be used to quickly detect the quality consistency of Glycyrrhiza formula granules, thereby improving the ability to control the quality and consistency of these granules.

Efficacy of psychotherapy in subthreshold depression patients: A protocol for an overview of systematic reviews and meta-analyses.

Background: Subthreshold depression is a risk factor for major depression. Psychotherapy is a kind of intervention for subthreshold depression. There have been many systematic reviews synthesized the evidence for its effectiveness toward subthreshold depression. However, there is currently no overview of these systematic reviews. Objective: To undertake an overview of meta-analyses and systematic reviews to identify the efficacy of psychotherapy in subthreshold depression patients. Methods: We will search several databases such as PubMed, Embase, the Cochrane Library, Web of Science, PsycINFO, CNKI, WanFang and VIP database, for systematic reviews and meta-analyses on psychotherapy in subthreshold depression patients. The search timeline will be from inception up to August 2022. Two researchers will screen related studies back-to-back. We will include studies that evaluate the efficacy of psychotherapy in subthreshold depression patients. We will evaluate the methodological quality, the reporting quality and the quality of evidence for outcomes by AMSTAR-2, the PRISMA 2020 checklist and the GRADE grading system. We will present the results of the overview in alignment with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The anticipated start and completion dates for this overview are 1 August 2022 and 30 December 2022, respectively. Results: From this study, we will evaluate the methodological quality and the level of evidence of the included systematic reviews and meta-analyses, and evaluate the efficacy of psychotherapy in patients with subthreshold depression. Implications: We will ascertain the efficacy of psychotherapy in subthreshold depression patients, to provide evidence to guide the treatment of subthreshold depression in the future. Registration number: Our research protocol has been registered with PROSPERO. The registration number of the protocol is CRD42021278871.

Vitamin D Promotes Remyelination by Suppressing c-Myc and Inducing Oligodendrocyte Precursor Cell Differentiation after Traumatic Spinal Cord Injury.

Demyelination due to oligodendrocytes loss occurs after traumatic spinal cord injury (TSCI). Several studies have suggested the therapeutic potential of vitamin D (VitD) in demyelinating diseases. However, experimental evidence in the context of TSCI is limited, particularly in the presence of prior VitD-deficiency. In the present study, a contusion and a transection TSCI rat model were used, representing mild and severe injury, respectively. Motor recovery was assessed in rats with normal VitD level or with VitD-deficiency after 8 weeks' treatment post-TSCI (Cholecalciferol, 500 IU/kg/day). The impact on myelin integrity was examined by transmission electron microscopy and studied in vitro using primary culture of oligodendrocytes. We found that VitD treatment post-TSCI effectively improved hindlimb movement in rats with normal VitD level irrespective of injury severity. However, cord-transected rats with prior deficiency did not seem to benefit from VitD supplementation. Our data further suggested that having sufficient VitD was essential for persevering myelin integrity after injury. VitD rescued oligodendrocytes from apoptotic cell death in vitro and enhanced their myelinating ability towards dorsal root axons. Enhanced myelination was mediated by increased oligodendrocyte precursor cells (OPCs) differentiation into oligodendrocytes in concert with c-Myc downregulation and suppressed OPCs proliferation. Our study provides novel insights into the functioning of VitD as a regulator of OPCs differentiation as well as strong preclinical evidence supporting future clinical testing of VitD for TSCI.

Protective Effect of Mitophagy Regulated by mTOR Signaling Pathway in Liver Fibrosis Associated with Selenium.

BACKGROUND: As a central organ of energy metabolism, the liver is closely related to selenium for its normal function and disease development. However, the underlying roles of mitochondrial energy metabolism and mitophagy in liver fibrosis associated with selenium remain unclear. METHODS: 28 rats were randomly divided into normal, low-selenium, nano-selenium supplement-1, and supplement-2 groups for a 12-week intervention. We observed pathological and ultrastructural changes in the liver and analyzed the effects of selenium deficiency and nano-selenium supplementation on liver metabolic activities and crucial proteins expression of mammalian target of the rapamycin (mTOR) signaling pathway. RESULTS: Selenium deficiency caused liver pathological damage and fibrosis with the occurrence of mitophagy by disrupting normal metabolic activities; meanwhile, the mTOR signaling pathway was up-regulated to enhance mitophagy to clear damaged mitochondria. Furthermore, nano-selenium supplements could reduce the severity of pathological damage and fibrosis in livers and maintain normal energy metabolic activity. With the increased concentrations of nano-selenium supplement, swelling mitochondria and mitophagy gradually decreased, accompanied by the higher expression of mTOR and phosphorylation-modified mTOR proteins and lower expression of unc-51 like autophagy activating kinase 1 (ULK1) and phosphorylation-modified ULK1 proteins. CONCLUSIONS: Mitophagy regulated by the mTOR signaling pathway plays a dual protective role on low-selenium inducing liver fibrosis and nano-selenium supplements preventing liver fibrosis. Mitochondrial energy metabolism plays an important role in these processes as well.

Vitamin D Enhances Hematoma Clearance and Neurologic Recovery in Intracerebral Hemorrhage.

BACKGROUND: Erythrophagocytosis by reparative monocyte-derived macrophage contributes to hematoma clearance and neurological recovery after intracerebral hemorrhage (ICH). Vitamin D (VitD) is a neuroprotective hormone and regulates the differentiation of monocyte-derived macrophage from monocytes. In this study, we examined the effects of VitD supplementation on monocyte-derived macrophage and hematoma clearance in rodent with ICH. METHODS: Neurobehavioral functions and hematoma volume were assessed using a collagenase injection model in both young- and middle-aged mice with or without VitD treatment given 2 hours post-ICH induction. We used flow cytometry to analyze CD36 expression and macrophage and undifferentiated monocyte cell numbers during in vivo erythrophagocytosis in collagenase and autologous blood injection models. Western blot analysis and immunofluorescence were used to assess the expression levels of the PPAR-γ (peroxisome proliferator-activated receptor γ)-CD36 axis and CD206. A macrophage differentiation study was conducted on murine bone marrow-derived monocytes. RESULTS: VitD promoted neurological recovery and facilitated hematoma clearance in both young- and middle-aged mice after ICH. Within the perihematomal region, mature macrophages, rather than undifferentiated monocytes, expressed higher levels of CD36 in driving erythrocyte clearance. VitD increased the macrophage number but decreased the monocyte number and elevated the levels of CD36 and PPAR-γ in the brain. In vitro, VitD accelerated the differentiation of reparative macrophages from bone marrow-derived monocytes. CONCLUSIONS: VitD promotes reparative macrophage differentiation, facilitates hematoma clearance, and improves neurobehavioral performance in mice with ICH, suggesting that VitD should be further examined as a potentially promising treatment for ICH.

Differential responses of polysaccharides and antioxidant enzymes in alleviating cadmium toxicity of tuber traditional Chinese medicinal materials.

Polygonatum cyrtonema Hua (PC) and Bletilla striata (BS) are widely used and planted as tuber traditional Chinese medicinal materials (TCMMs). Cadmium (Cd) is one of the major causes of soil pollution and challenge to the quality and safety of TCMMs. Understanding the absorption and distribution of Cd is important for addressing the risks posed by its residues. As a result, the higher Cd translocation factor (TF) results in the lower Cd bioconcentration factor (BCF) in the PC tuber than that of BS attributed to a lower Cd concentration in the PC tuber, which guaranteed its safe utilization and edible safety under 1 mg·kg-1 Cd soil. Cd stress overall activated peroxidase (POD), catalase (CAT), and water-extractable polysaccharides in PC (PCP1) to exhibit better antioxidation, while the superoxide dismutase (SOD) in BS increased by approximately 206-277% to alleviate more severe oxidative damage. Particularly, Cd induced an increase in PCP1 higher than that of water-extractable polysaccharides of BS (BSP1) by approximately 335% to 1351%. PC exhibited effective strategies for alleviating Cd toxicity, including transferring Cd to nonmedicinal parts, increasing polysaccharides, and synergistically activating the enzymatic antioxidant system. This study expands the application for the safe utilization of low-Cd contaminated soil and provides novel insights for tuber TCMMs to alleviate Cd toxicity.

Selenium alleviates toxicity in Amaranthus hypochondriacus by modulating the synthesis of thiol compounds and the subcellular distribution of cadmium.

As a beneficial element, Selenium (Se) reduces toxic cadmium (Cd) absorption in many crops, but the effects of Se on Cd hyperaccumulator plants are unclear. This study examined the effects of Se on Amaranthus hypochondriacus (K472). The results showed that Se increased antioxidant enzyme activities, reduced Cd concentrations and toxicity, restored cell viability, and enhanced photosynthesis; these effects increased the biomass of roots, stems, and leaves by 59.87%, 53.85%, 44.19%, respectively, and these values exceeded the biomass of roots and stems in untreated control plants by 56.69% and 15.37%, respectively. Moreover, Se promoted PC synthesis, stably chelated Cd in the form of PC3 and PC4 and transported PC-Cd to vacuoles. Furthermore, Se protected organelles and reduced Cd migration by increasing Cd levels in cell walls and vacuoles. Interestingly, although the Cd content in K472 was decreased, Se maintained the total extracted Cd concentrations and its remediation efficiency by improving biomass and increased tolerance to Cd by approximately 5 times. The experimental results provide novel insights and methods for mitigating toxicity, promoting growth, and broadening the engineering application scope of K472; these results also provide a theoretical basis for further application of Se in soil with high Cd concentrations.

Hydrogen-Rich Water Ameliorates Murine Chronic Graft-versus-Host Disease through Antioxidation.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment option for various hematopoietic diseases and certain hereditary diseases. Chronic graft-versus-host disease (cGVHD) has become the main life-threatening complication and cause of death in later stage postallo-HSCT. Current treatment options for cGVHD are limited. Hydrogen gas (H2) has been demonstrated that has antioxidative, anti-inflammatory, and antifibrosis effects. The aim of this study was to confirm whether oral administration hydrogen-rich water exerted therapeutic effects on a scleroderma cGVHD mouse model and tried to explain the mechanism underly it. METHODS: A mouse cGVHD model was established by haploidentical bone marrow transplantation. To evaluate therapeutic effects of H2 on cGVHD, survival rate, changes in clinical scores, and skin pathologic characteristics of cGVHD mice were observed. To evaluate its therapeutic mechanism, we detected the expression levels of antioxidative enzymes heme oxygenase-1(HO-1) and NAD (P)H: quinone acceptor oxidoreductase 1(NQO1) in skin homogenates. We also detected the expression level of the apoptotic protein caspase-3 in skin homogenates. RESULTS: 1-month survival rate of cGVHD mice in the hydrogen group reached 93.3%, significantly higher than 66.7% in the nonhydrogen group (p < 0.05). Clinical score of cGVHD mice was improved by hydrogen-rich water at 96 days posttransplantation (2.2 versus 4.5, p < 0.05). The skin pathological condition of cGVHD mice was significantly improved by hydrogen-rich water. At 96 days posttransplantation, average skin pathological hematoxylin and eosin (HE) staining score in the hydrogen group was 1.05, which was significantly lower than 3.2 in the nonhydrogen group (p < 0.01). Average Masson staining score was 0.6 point in the hydrogen group, lower than 0.9 point in the nonhydrogen group (p < 0.05). Both the relative expression levels of HO-1 and NQO1 proteins in skin specimens of cGVHD mice in the hydrogen group were lower than that in the nonhydrogen group (2.47 versus 6.21 and 1.83 versus 3.59, p < 0.05). The relative expression level of caspase-3 protein in skin specimens of cGVHD mice increased to 7.17 on the 96th day after transplantation, significantly higher than 4.36 in the hydrogen group. CONCLUSION: In this study, we found that oral hydrogen-rich water improved the survival rate and clinical symptoms of cGVHD mice by antioxidant and antiapoptosis. This study would pave the way for further clinical study, which may provide a new treatment option for cGVHD.

The Effects of Nonnutritive Sweeteners on the Cariogenic Potential of Oral Microbiome.

Nonnutritive sweeteners (NNSs) are sugar substitutes widely used to reduce the negative health effects of excessive sugar consumption. Dental caries, one of the most prevalent chronic diseases globally, results from a pathogenic biofilm with microecological imbalance and frequent exposure to sugars. Some research has shown that certain NNSs possess less cariogenic potential than sucrose, indicating their putative effect on oral microbiome. To uncover the alterations of acidogenic pathogens and alkali-generating commensals, as well as the biofilm cariogenic potential under the influence of NNSs, we selected four common NNSs (acesulfame-K, aspartame, saccharin, and sucralose) and established single-, dual-, and multispecies in vitro culture model to assess their effects on Streptococcus mutans (S. mutans) and/or Streptococcus sanguinis (S. sanguinis) compared to sucrose with the same sweetness. The results showed that NNSs significantly suppressed the planktonic growth, acid production, and biofilm formation of S. mutans or S. sanguinis compared with sucrose in single-species cultures. Additionally, decreased S. mutans/S. sanguinis ratio, less EPS generation, and higher pH value were observed in dual-species and saliva-derived multispecies biofilms with supplementary NNSs. Collectively, this study demonstrates that NNSs inhibit the cariogenic potential of biofilms by maintaining microbial equilibrium, thus having a promising prospect as anticaries agents.

Xuefu Zhuyu decoction for nonalcoholic fatty liver disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) includes nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), which ranks only second to viral hepatitis and poses an increasingly serious challenge to global public health and economy. NAFLD has attracted more and more attention, but there is no drugs with exact curative effects are available. The commonly used drugs for the treatment of NAFLD in clinical practice are statins, such drugs, inevitably increase the burden on the live. Compared to statins, traditional Chinese medicines are believed to be "all natural" with fewer side effects, are associated with strong patient compliance. Accordingly, a great deal of clinical studies have shown that Xuefu Zhuyu decoction (XFZYD) can significantly improve the clinical symptoms and enhance the therapeutic effect. Meanwhile, a system review and meta-analysis are conducted by us to further clarify the effectiveness and safety of XFZYD for NAFLD. METHODS: We will apply to database mainly range from the English literature searches Cochrane Library, PubMed, excerpt medica database, and Web of Science to the Chinese literature China national knowledge infrastructure, Chinese biomedical literature database, VIP, and Wanfang database, randomized controlled trials (RCTs) are enrolled to evaluate the effectiveness and safety of XFZYD in the treatment of NAFLD, the enrollment of RCTs is from the establishment of the database to February 01, 2021. Simultaneously we will retrieval clinical registration tests and grey literatures. The 2 researchers worked independently on literature selection, data extraction, and quality assessment. The dichotomous data is expressed in terms of relative risk, the continuous is represented by mean difference or standard mean difference, whether there is heterogeneity is the factor that determines the synthesis of data in fixed effect model or random effect model. Alanine aminotransferase (ALT) or Aspartic acid aminotransferase (AST) coupled with Glutamyltransferase (GGT) is considered as one of the main indicators of the NAFLD, while the pathology, imaging and diagnosis of metabolic syndrome are also auxiliary results. The last, meta-analysis was conducted by RevMan software version 5.3. RESULTS: This study will provide evidence for treatment of NAFLD with XFZYD in terms of effectiveness and safety. CONCLUSION: This systematic review aims to confirm the efficacy and safety of XFZYD in the treatment of NAFLD. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/7CWRK.

Which of the acupuncture treatment regimen for lumbar disc herniation is more effective and safer: A protocol for systematic review and network meta-analysis.

INTRODUCTION: Lumbar disc herniation (LDH) is the most common cause of low back pain and severely affects people's quality of life and ability to work. Although many clinical trials and medical reports conducted over the years have shown that acupuncture treatments are effective for LDH, the comparative effectiveness of these different acupuncture therapies is still unclear. This protocol of a network meta-analysis was designed to compare the effects and safety of acupuncture treatment regimens on LDH using both direct and indirect evidence. METHODS AND ANALYSIS: This protocol is reported according to the 2015 PRISMA-P and PRISMA guidelines for acupuncture. Eight databases and two platforms will be searched for articles published from their establishment to 1 December 2020 with medical subject heading terms and keywords. Three reviewers will verify the eligible randomized controlled trials independently. NoteExpress (3.2.0) software will be utilized to manage the literature. The overall quality of evidence will be evaluated by Confidence In Network Meta-Analysis (CINeMA). Additionally, we will conduct a meta-analysis of the effectiveness, recurrence rate, and symptom score of acupuncture in treating LDH using Review Manager (RevManV.5.4.1) and R4.0.2 software (The R Foundation for Statistical Computing). RESULTS: The results of the study will be published in journals or relevant conferences. CONCLUSION: This proposed systematic review will evaluate the comparative efficacy and safety of various acupuncture methods and combination protocols for LDH.