Oral probiotics increased the proportion of Treg, Tfr, and Breg cells to inhibit the inflammatory response and impede gestational diabetes mellitus.

BACKGROUND: Children of mothers with gestational diabetes mellitus (GDM) are more prone to acquire type 2 diabetes and obesity as adults. Due to this link, early intervention strategies that alter the gut microbiome may benefit the mother and kid long-term. This work uses metagenomic and transcriptome sequencing to investigate how probiotics affect gut microbiota dysbiosis and inflammation in GDM. METHODS: GDM and control metagenomic sequencing data were obtained from the SRA database. This metagenomic data helped us understand gut microbiota abundance and function. KEGG detected and extracted functional pathway genes. Transcriptome sequencing data evaluated GDM-related gene expression. Finally, GDM animal models were given probiotics orally to evaluate inflammatory response, regulatory immune cell fractions, and leptin protein levels. RESULTS: GDM patients had more Fusobacteria and Firmicutes, while healthy people had more Bacteroidetes. Gut microbiota composition may affect GDM by altering the L-aspartate and L-asparagine super pathways. Mannan degradation and the super pathway of L-aspartate and L-asparagine synthesis enhanced in GDM mice with leptin protein overexpression. Oral probiotics prevent GDM by lowering leptin. Oral probiotics increased Treg, Tfr, and Breg cells, which decreased TNF-α and IL-6 and increased TGF-ß and IL-10, preventing inflammation and preserving mouse pregnancy. CONCLUSION: Dysbiosis of the gut microbiota may increase leptin expression and cause GDM. Oral probiotics enhance Treg, Tfr, and Breg cells, which limit the inflammatory response and assist mice in sustaining normal pregnancy. Thus, oral probiotics may prevent GDM, enabling targeted gut microbiota modulation and maternal and fetal health.

Exogenous Hydrogen Sulfide Mitigates Oxidative Stress and Mitochondrial Damages Induced by Polystyrene Microplastics in Osteoblastic Cells of Mice.

Polystyrene microplastics (mic-PS) have become harmful pollutants that attracted substantial attention about their potential toxicity. Hydrogen sulfide (H2S) is the third reported endogenous gas transmitter with protective functions on numerous physiologic responses. Nevertheless, the roles for mic-PS on skeletal systems in mammals and the protective effects of exogenous H2S are still indistinct. Here, the proliferation of MC3T3-E1 cell was analyzed by CCK8. Gene changes between the control and mic-PS treatment groups were analyzed by RNA-seq. The mRNA expression of bone morphogenetic protein 4 (Bmp4), alpha cardiac muscle 1 (Actc1), and myosin heavy polypeptide 6 (Myh6) was analyzed by QPCR. ROS level was analyzed by 2',7'-dichlorofluorescein (DCFH-DA). The mitochondrial membrane potential (MMP) was analyzed by Rh123. Our results indicated after exposure for 24 h, 100 mg/L mic-PS induced considerable cytotoxicity in the osteoblastic cells of mice. There were 147 differentially expressed genes (DEGs) including 103 downregulated genes and 44 upregulated genes in the mic-PS-treated group versus the control. The related signaling pathways were oxidative stress, energy metabolism, bone formation, and osteoblast differentiation. The results indicate that exogenous H2S may relieve mic-PS toxicity by altering Bmp4, Actc1, and Myh6 mRNA expressions associated with mitochondrial oxidative stress. Taken together, this study demonstrated that the bone toxicity effects of mic-PS along with exogenous H2S have protective function in mic-PS-mediated oxidative damage and mitochondrial dysfunction in osteoblastic cells of mice.

Factors associated with the high susceptibility to depression of women during the perimenopause.

OBJECTIVE: This study investigated the factors associated with the high susceptibility of perimenopausal women to depression. METHODS: A total of 66 perimenopausal women participated in this study. The Zung self-rating depression scale (SDS) was used to evaluate the intensity of depressive symptoms. The modified Kupperman index (KI) was used to assess common perimenopausal symptoms. Psychosocial factors were assessed via the Eysenck Personality Questionnaire, attitudes toward menopause checklist, and metacognition questionnaire (MCQ). Levels of serum estradiol, testosterone, and progesterone were determined. RESULTS: There were statistically significant associations between SDS standard score and the KI scale score (ß = .361, p = .001), years of education (ß = -.309, p = .005), and F3 cognitive self-consciousness score of MCQ (ß = -.234, p = .032; adjusted R2  = .264, F = 8.759, p < .001). CONCLUSIONS: High susceptibility to depression of perimenopausal women may be related to lower educational level, more severe perimenopausal symptoms, and altered metacognition.

Exogenous hydrogen sulfide protects human umbilical vein endothelial cells against high glucose­induced injury by inhibiting the necroptosis pathway.

Hyperglycemia is a key factor in the development of diabetic complications, including the processes of atherosclerosis. Receptor­interacting protein 3 (RIP3), a mediator of necroptosis, is implicated in atherosclerosis development. Additionally, hydrogen sulfide (H2S) protects the vascular endothelium against hyperglycemia­induced injury and attenuates atherosclerosis. On the basis of these findings, the present study aimed to confirm the hypothesis that necroptosis mediates high glucose (HG)­induced injury in human umbilical vein endothelial cells (HUVECs), and that the inhibition of necroptosis contributes to the protective effect of exogenous H2S against this injury. The results revealed that exposure of HUVECs to 40 mM HG markedly enhanced the expression level of RIP3, along with multiple injuries, including a decrease in cell viability, an increase in the number of apoptotic cells, an increase in the expression level of cleaved caspase­3, generation of reactive oxygen species (ROS), as well as dissipation of the mitochondrial membrane potential (MMP). Treatment of the cells with sodium hydrogen sulfide (NaHS; a donor of H2S) prior to exposure to HG significantly attenuated the increased RIP3 expression and the aforementioned injuries by HG. Notably, treatment of cells with necrostatin­1 (Nec­1), an inhibitor of necroptosis, prior to exposure to HG ameliorated the HG­induced injuries, leading to a decrease in ROS generation and a loss of MMP. However, pre­treatment of the cells with Nec­1 enhanced the HG­induced increase in the expression levels of cleaved caspases­3 and ­9. By contrast, pre­treatment with Z­VAD­FMK, a pan ­caspase inhibitor, promoted the increased expression of RIP3 by HG. Taken together, the findings of the present study have demonstrated, to the best of our knowledge for the first time, that exogenous H2S protects HUVECs against HG­induced injury through inhibiting necroptosis. The present study has also provided novel evidence that there is a negative interaction between necroptosis and apoptosis in the HG­treated HUVECs.

[Angiotensin-(1-7) protects cardiac myocytes against high glucose-induced injury by inhibiting ClC-3 chloride channels].

OBJECTIVE: To explore whether angiotensin-(1-7) [Ang-(1-7)] protects cardiac myocytes against high glucose (HG)-induced injury by inhibiting ClC-3 chloride channels. METHOD: H9c2 cardiac cells were exposed to 35 mmol/L glucose for 24 h to establish a cell injury model. The cells were treated with Ang-(1-7) or the inhibitor of chloride channel (NPPB) in the presence of HG for 24 h to observe the changes in HG-induced cell injury. Cell counter kit 8 (CCK-8) assay was used to test the cell viability, and the morphological changes of the apoptotic cells were detected using Hoechst 33258 staining and fluorescent microscopy. The intracellular level of reactive oxygen species (ROS) was examined by DCFH-DA staining, SOD activity in the culture medium was measured using commercial kits, and the mitochondrial membrane potential (MMP) of the cells was tested with rodamine 123 staining. The expression level of cardiac ClC-3 chloride channels was detected with Western blotting. RESULTS: Exposure of H9c2 cardiac cells to 35 mmol/L glucose for 24 h markedly enhanced the expressions of cardiac ClC-3 channel protein (P<0.01). Co-treatment of the cells with 1 µmol/L Ang-(1-7) and HG for 24 h significantly attenuated HG- induced upregulation of ClC-3 channel protein expression (P<0.01). Co-treatment of the cells exposed to HG with 1 µmol/L Ang-(1-7) or 100 µmol/L NPPB for 24 h obviously ameliorated HG-induced injuries as shown by increased cell viability, enhanced SOD activity, decreased number of apoptotic cells, and reduced intracellular ROS generation and loss of MMP (P<0.01). CONCLUSION: ClC-3 channels are involved in HG-induced injury in cardiac cells. Ang-(1-7) protects cardiac cells against HG-induced injury by inhibiting ClC-3 channels.

[Therapeutic effect of vildagliptin and insulin aspart injection in elderly patients with type 2 diabetes].

OBJECTIVE: To observe the therapeutic effect and safety of vildagliptin combined with insulin aspart injection in elderly patients with type 2 diabetes. METHODS: Sixty-six elderly patients with type 2 diabetes who had poor blood glucose control with insulin aspart injection were divided into two groups to have additional Vildagliptin (50 mg, twice daily, n=36, observation group) or Acarbose (50 mg, three times a day, n=30, control group). Blood glucose (including FBG and 2hPG), HbA1C, fasting c-peptide, postprandial c-peptide, BMI and GFR were observed after 12 weeks. RESULTS: In the observation group, FBG, 2hPG and HbA1C decreased significantly (P<0.05), fasting and postprandial c-peptide increased (P<0.05), and BMI and GFR showed no obvious changes (P>0.05). In the control group, 2hPG and HbA1C were significant lowered (P<0.05) but FBG, fasting and postprandial c-peptide, BMI or GFR showed no changes (P>0.05). Compared with those in the control group, FBG in the observation group showed a significant reduction (P<0.05), but no significant differences were found in 2hPG, HbA1C, BMI or GFR (P>0.05). No hypoglycemia occurred in the two groups during the treatment. CONCLUSION: Vildagliptin with insulin aapart injection has equivalent effect with Acarbose combined with insulin aspart injection in decreasing 2hPG and HbA1C without increasing the body weight or the risk to hypoglycemia or causing lowered GFR. Vildagliptin has better effect in decreasing FBG and improving the function of the islet cells.

[Therapeutic effect of zoledronic acid on primary osteoporosis in elderly patients].

OBJECTIVE: To observe the effect of zoledronic acid on bone mineral density (BMD) and bone metabolic markers in elderly patients with primary osteoporosis. METHODS: Forty-eight elderly patients with osteoporosis were randomly assigned to zoledronic acid group (n=23) to receive treatment with 5 mg zoledronic acid once a year and the control group (n=25). In both groups, the patients were given Vitamin D3 and caltrate on a daily basis for a year. The bone mineral density (BMD) and bone metabolic markers were observed after the treatment. RESULTS: Compared with the control group, zoledronic acid group had significantly higher L1-4, neck, Inter and Ward's BMD (P<0.05) with reduced B-NTX (P<0.05). The N-MID and CT showed no significant differences between the two groups (P<0.05). CONCLUSION: Zoledronic acid administration once a year can increase BMD and lower the serum bone turnover metabolism, and can be used in the treatment of primary osteoporosis in elderly patients.

[Factors associated with acute febrile reaction in elderly patients receiving intravenous zoledronic acid for osteoporosis].

OBJECTIVE: To survey the incidence of acute febrile reaction in elderly patients receiving intravenous zoledronic acid for osteoporosis and identify the related factors. METHODS: Thirty-eight elderly patients with osteoporosis were hospitalized and treated with intravenous infusion of 5 mg zoledronic acid in 2010. The incidence of acute fever reaction was observed in these patients , and the time of fever onset, duration, average maximum temperature, and antipyretic drug used were recorded. The patients with and without acute febrile reaction were compared for age, duration of osteoporosis, sex ratio, use of parathyroid hormone before zoledronic acid treatment, ß-fragment of collagen breakdown, calcitonin, osteocalcin, serum calcium, and use of anti-osteoporosis drugs before the treatment. RESULTS: Acute fever reaction occurred in 12 (31.6%) of the patients. Two of the patients had fever on the day of zoledronic acid treatment, and the other patients developed fever after the first day of treatment, with a mean duration of 1 day and a maximum temperature of (38.5∓0.84) degrees celsius;. The fever was treated with a mean of 3.55∓1.21 pseudoephedrine tablets. The patients with fever showed significantly higher parathyroid hormone levels before treatment than those without fever (P<0.05); osteocalcin, calcitonin, ß-fragment of collagen breakdown, or serum calcium showed no significant difference between the two groups. CONCLUSION: Acute febrile reaction, often moderate and transient, is common in elderly patients receiving intravenous zoledronic acid for osteoporosis, and its occurrence is possibly associated with parathyroid hormone levels before the treatment.

[Vitamin D receptor gene polymorphism is not associated with bone mineral density of pre-menopausal women in Guangzhou].

OBJECTIVE: To investigate the prevalence of vitamin D receptor (VDR) gene polymorphism in pre-menopausal women in Guangzhou and study its relationship with bone mineral density(BMD). METHODS: The genotypes of VDR gene in 193 per-menopausal women in Guangzhou were analyzed by polymerase chain reaction-restriction fragment length polymorphism. BMD of the lumbar spine, femoral neck, greater trochanter and Ward's triangle were measured by dual-energy X-ray absorptiometry. RESULTS: In the 193 subjects, 120 (66.2%) were identified as VDR bb genotype, 64 (33.2%) as Bb, and 9 (4.6%) as BB. The b allele frequencies reached 78.76%, and B allele frequencies was 21.24%. The distribution followed the Hardy-Weinberg equilibrium. No significant difference was found in BMD among the subjects with different genotypes. CONCLUSION: VDR genotype is not related to BMD, and VDR polymorphism can not be used as a genetic marker for predicting the risk of osteoporosis in pre-menopausal women in Guangzhou.

[Relationship of collagen type I alpha 1 and alpha 2 gene polymorphisms with bone mineral density].

OBJECTIVE: To investigate collagen type I alpha 1 (COL1A1) and alpha 2 (COL1A2) gene polymorphisms in Chinese and their relationship with bone mineral density. METHODS: Totalling 628 residents of Han nationality in Guangzhou aged 53.4-15.9 (range 20-79) years were surveyed for COL1A1 and COL1A2 gene genotypes by polymerase chain reaction-restriction fragment length polymorphism. Bone mineral density of the lumbar vertebrae, greater trochanter, femur neck and Ward's triangle was measured by dual-energy X-ray absorptiometry. RESULTS: COL1A1 Sp1 polymorphism was not found in these subjects, and the genotype of all samples were type SS. COL1A2 genotyping revealed the distribution of EE genotype in 49.7%, Ee in 40.9% and ee in 9.4% of the subjects. The frequency distribution of EcoR1 alleles followed the Hardy-Weinberg equilibrium. The mean bone mineral density did no significantly differ among these genotype groups (P>0.05 by analysis of variance). CONCLUSION: COL1A1 Sp1 binding site polymorphism is absent and COL1A2 EcoR1 site polymorphism is not associated with bone mineral density in Chinese of Han nationality.