Comparison of Bisphosphonates Versus Teriparatide in Therapy of the Glucocorticoid-Induced Osteoporosis (GIOP): A Meta-Analysis of Randomized Controlled Trials.

Osteoporosis (OP) is characterized as decreased bone mineral density (BMD) and increased risk of bone fracture. Secondary OP resulting from excess endogenous or exogenous glucocorticoid is defined as glucocorticoid-induced osteoporosis (GIOP). Current therapeutic strategies for GIOP are similar to menopausal osteoporosis, including calcium and vitamin D supplementation, bisphosphonates, and parathyroid hormone (PTH) analogues (teriparatide). Previously, several published meta-analyses compared anti-osteoporotic agents for the menopausal or aging-dependent OP. However, the physiopathologic bone metabolism of GIOP is different. In this study, we investigated the efficacy of BMD enhancement, bone fracture rate and safety of bisphosphonates versus teriparatide in the therapy of GIOP. We searched databases including PubMed, Embase, and the Cochrane Library until Jan 2023, and selected ten random clinical trials (RCT)s that compared the efficacy and/or safety of bisphosphonate versus teriparatide for GIOP patients. Teriparatide therapy increased lumber spinal BMD by 3.96% (95% CI 3.01-4.9%, p<0.00001), 1.23% (95% CI 0.36-2.1%, p=0.006) at total hip, and 1.45% (95% CI 0.31-2.58%, p=0.01) at femoral neck, respectively, compared to bisphosphonates at 18-month therapy for GIOP. Teriparatide also reduced bone fracture especially in vertebral bone (p=0.0001, RR 6.27, 95% CI 2.44-16.07), and increased bone formation and resorption marker levels. There was no difference in the incidence of adverse effects in bisphosphonate and teriparatide groups. Teriparatide showed better performance over bisphosphonate in BMD enhancement, bone fracture reduction, and bone remodeling improvement, without increasing the incidence of adverse effects.

Identification of Two Novel Mutations of ABCD1 Gene in Pedigrees with X-Linked Adrenoleukodystrophy and Review of the Literature.

Background: X-linked adrenoleukodystrophy (ALD) is an inherited peroxisomal metabolism disorder, resulting from the loss-of-function mutation of ATP-binding cassette protein subfamily D1 (ABCD1) gene. The dysfunction of ALD protein, a peroxisomal ATP-binding cassette transporter, results in the excessive saturated very long-chain fatty acids (VLCFAs) accumulation in organs including the brain, spine, and adrenal cortex. X-ALD is characterized as the childhood, adolescent, adult cerebral ALD, adrenomyeloneuropathy (AMN), adrenal insufficiency, and asymptomatic phenotypes, exhibiting a high variety of clinical neurological manifestations with or without adrenocortical insufficiency. Results: In this study, we reported two cases of X-ALD, which were first diagnosed as adrenal insufficiency (Addison's disease) and treated with adrenocortical supplement. However, both of the cases progressed as neurological symptoms and signs after decades. Elevated VLCFAs level, brain MRI scan, and genetic analysis confirmed final diagnosis. In addition, we identified two novel mutations of ABCD1 gene, NM_000033.3 (ABCD1): c.874_876delGAG (p.Glu292del) and NM_000033.3 (ABCD1): c.96_97delCT (p.Tyr33Profs∗161), in exon 1 of ABCD1 gene. Sanger sequencing confirmed that the proband's mother of the first case was heterozygous carrying the same variant. Adrenal insufficiency-only type is very rare; however, it may be the starting performance of X-ALD. In addition, we summarized reported mutation sites and clinical manifestations to investigate the correlationship of phenotype-genotype of X-ALD. Conclusions: The early warning manifestations should be noticed, and the probability of X-ALD should be considered. This report could be beneficial for the early diagnosis and genetic counseling for patients with X-ALD.

Resveratrol Enhances Wound Healing in Type 1 Diabetes Mellitus by Promoting the Expression of Extracellular Vesicle-Carried MicroRNA-129 Derived from Mesenchymal Stem Cells.

Recent studies have shown the promotive effect of resveratrol on wound healing. This study aims to explore the underlying molecular mechanism of resveratrol in type 1 diabetes mellitus (T1DM) through microRNA (miR)-129-containing extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) based on in silico analysis. The rat model of T1DM was established by intraperitoneal injection of sodium citrate containing streptozotocin, and the wound was made around the deep fascia. Rat MSCs were isolated and treated with resveratrol (SRT501), and the corresponding EVs (SRT501-EVs) were isolated, where the expression of miR-129 was determined. By performing function experiments, the effect of SRT501-EVs and miR-129 on the biological functions of human umbilical vein endothelial cells (HUVECs) was determined. Finally, the binding relationship between miR-129 and tumor necrosis factor receptor-associated factor 6 (TRAF6) was also determined by the dual-luciferase reporter gene assay. miR-129 was shown as a candidate related to both resveratrol and wound healing in T1DM. SRT501-EVs promoted the skin wound healing of T1DM rats and also further improved the proliferative, migratory, and tube formation potentials of HUVECs. Resveratrol inhibited the expression of TRAF6 in HUVECs stimulated by MSC-conditioned medium and promoted the transfer of miR-129 via EVs, while TRAF6 was confirmed as a target gene of miR-129. Furthermore, inhibition of miR-129 attenuated the proangiogenic effect of resveratrol on HUVECs. Resveratrol exerts promotive role in wound healing in T1DM through downregulation of TRAF6 via MSC-EV-carried miR-129, suggesting a regulatory network involved in the wound healing process in T1DM.

The effects of adipose-derived mesenchymal stem cells combined with sodium selenite on Hashimoto's thyroiditis.

Recent research found that sodium selenite (Na2SeO3) could ameliorate oxidative damage in patients with Hashimoto's thyroiditis (HT). Additionally, the effects of adipose-derived mesenchymal stem cells (AMSCs) in an animal model of HT were also reported. However, the effects of AMSCs combined with Na2SeO3 on HT are unknown. We investigated the combined effects of AMSCs and Na2SeO3 in a rat model of HT and the in vitro effect of Na2SeO3 on AMSCs using gene microarray analyses. In the HT rat model, the combination of AMSCs and Na2SeO3 restored thyroid tissue structure to that of normal controls and increased the levels of most antioxidant and inflammatory cytokines examined, but decreased the levels of interleukin 10 (IL-10) in HT thyroid tissues. At 0.5-20 µM, Na2SeO3 promoted AMSC growth and increased the levels of reduced glutathione and total antioxidant capacity in AMSCs (P<0.05). Na2SeO3 increased the levels of hepatocyte growth factor (HGF), transforming growth factor beta (TGF-ß), and stem cell factor (SCF) in AMSC culture supernatants. The results of the gene microarray analyses showed that the expression levels of certain genes involved in mitosis, DNA replication and repair, ubiquitination, synthesis and metabolism, and mitochondrial transport changed in response to Na2SeO3 treatment. In conclusion, the combination of AMSCs and Na2SeO3 restored the function and structure of the thyroid in an HT model, and Na2SeO3 promoted the growth, improved the secretion, and the antioxidant capacity of AMSCs in vitro. This combination treatment may provide a new therapy for patients with HT.

Expressions of miRNAs in papillary thyroid carcinoma and their associations with the clinical characteristics of PTC.

BACKGROUND: The sensitivity and specificity of biomarkers which have been used in clinical practice for diagnosis of papillary thyroid carcinoma (PTC) are low, it is essential to develop novel diagnostic and prognostic biomarkers for PTC. OBJECTIVE: To explore the expressions of miR-940, miR-15a, miR-16 and IL-23 in PTC tissues and plasma and their associations with the clinical characteristics of PTC. METHODS: We investigated the expressions of miR-940, miR-15a, miR-16 and IL-23 in plasma and thyroid tissues of PTC, nodular goiter and healthy people with qRT-PCR, and further analyzed the associations between their levels and the clinical characteristics of PTC. RESULTS: Level of IL-23 expression was higher while levels of miR-940, miR-15a and miR-16 expression in the PTC tissues were lower compared with the nodular goiter tissues and perineoplastic thyroid tissues. And the levels of miR-940, miR-15a, miR-16 and IL-23 expression in the PTC tissues were associated with some clinical characteristics of PTC, including bilateral tumor, multicentricity, extrallyroidal invasion, cervical lymph node metastasis, distant metastasis and clinical advanced stages (III/IV). CONCLUSIONS: Expressions of miR-940, miR-15a, miR-16 and IL-23 in PTC tissues might be useful biomarkers and promising targets in the diagnosis of papillary thyroid carcinoma.

Increased risk of vertebral fracture in patients with diabetes: a meta-analysis of cohort studies.

PURPOSE: The relationship between diabetes and risk of fracture has been reported differently in study design and risk estimates, and the relationship between diabetes and risk of vertebral fracture remained unclear. Therefore, we performed a meta-analysis of prospective or retrospective cohort studies to assess the potential relationship between diabetes and vertebral fracture. METHODS: We searched medical databases for prospective or retrospective cohort studies on the association between diabetes and vertebral fracture risk. Pooled relative risks (RR) and corresponding 95 % confidence intervals (95 % CI) were calculated with a random-effects model of meta-analysis. RESULTS: Meta-analysis of eight studies showed that the pooled RR of vertebral fracture for diabetic individuals was 2.03 (95 % CI 1.60-2.59; p < 0.0001). Subgroup analysis by gender showed that the corresponding RRs for male and female were 2.70 (95 % CI 1.34-5.43; p = 0.005) and 1.93 (95 % CI 1.18-3.13; p = 0.008), respectively. Subgroup analysis by study design showed that the corresponding RRs for prospective design and retrospective design were 1.81 (95  % CI 1.19-2.75; p = 0.006) and 2.23 (95  % CI 1.60-3.10; p < 0.0001), respectively. Subgroup analysis by time of follow-up showed that the RR of vertebral fracture for patients with >20 and <20 years of follow-up were 2.23 (95 % CI 1.98-3.62; p < 0.0001) and 1.67 (95  % CI 1.29-2.16; p < 0.0001), respectively. CONCLUSIONS: Diabetes is an independent risk factor for vertebral fracture, primarily being due to diabetic osteoporosis.

Effects of autologous adipose-derived stem cell infusion on type 2 diabetic rats.

The effects and possible mechanisms of adipose-derived stem cells (ASC) infusion on type 2 diabetic rats were investigated in this study. Twenty normal male Sprague-Dawley rats were included in normal control group, and 40 male diabetic rats were randomly divided into diabetic control group and ASC group (which received ASC infusion). After therapy, levels of fasting plasma glucose (FPG), HbA1c, serum insulin and C-peptide, recovery of islet cells, inflammatory cytokines, and insulin sensitivity were analyzed. After ASC infusion, compared with diabetic control group, hyperglycemia in ASC group was ameliorated in 2 weeks and maintained for about 6 weeks, and plasma concentrations of insulin and C-peptide were significantly improved (P<0.01). Number of islet ß cells and concentration of vWF in islets in ASC group increased, while activity of caspase-3 in islets was reduced. Moreover, concentrations of TNF-α, IL-6 and IL-1ß in ASC group obviously decreased (P<0.05). The expression of GLUT4, INSR, and phosphorylation of insulin signaling molecules in insulin target tissues were effectively improved. ASC infusion could aid in T2DM through recovery of islet ß cells and improvement of insulin sensitivity. Autologous ASC infusion might be an effective method for T2DM.

CARD8 rs2043211 polymorphism is associated with gout in a Chinese male population.

BACKGROUND &AIM: Previous studies have suggested genetic factors are involved in the development of gout. We performed a case-control study to investigate the genetic association between CARD8 rs2043211 polymorphism and gout. METHODS: A total of 396 male patients with gout and 403 age- and sex- matched healthy controls were included in this study. Genotyping was performed using TaqMan SNP Genotyping Assays. An association analysis was carried out using the χ² test. The genotype-phenotype analysis was also conducted. RESULTS: The genotype distribution of CARD8 rs2043211 polymorphism confirmed to HWE in the controls (P = 0.27). There was an obvious difference in the genotype distribution of CARD8 rs2043211 polymorphism between cases and controls (P = 0.017). In addition, there was an obvious association between CARD8 rs2043211 polymorphism and gout under the recessive comparison model (AA vs. TT/TA: OR = 0.65, 95%CI 0.47-0.88, P = 0.006). Patients carrying genotype TT of CARD8 rs2043211 polymorphism had higher triglycerides levels compared to those carrying the AA genotype (2.77±2.08 mmol/L vs. 2.07±1.15 mmol/L, P = 0.01). Patients with the TT genotype also had significantly higher systolic blood pressure compared with those with the AA genotype (142.11±21.10 mmHg vs. 135.38±14.66 mmHg, P = 0.03). Patients carrying TT genotype also had an increased risk of renal calculus compared with those carrying the AA genotype. CONCLUSION: CARD8 rs2043211 polymorphism is significantly associated with susceptibility to gout in Chinese Han males.

Effect and mechanisms of human Wharton's jelly-derived mesenchymal stem cells on type 1 diabetes in NOD model.

Type 1 diabetes is an autoimmune disease that results from an inflammatory destruction of ß-cells in islets. Mesenchymal stem cells derived from Wharton's jelly (WJ-MSCs) own a peculiar immunomodulatory feature and might reverse the inflammatory destruction and repair the function of ß-cells. Sixty NOD mice were divided into four groups, including normal control group, WJ-MSCs prevention group (before onset), WJ-MSCs treatment group (after onset), and diabetic control group. After homologous therapy, onset time of diabetes, levels of fasting plasma glucose (FPG), fed blood glucose and C-peptide, regulation of cytokines, and islet cells were examined and evaluated. After WJ-MSCs infusion, FPG and fed blood glucose in WJ-MSCs treatment group decreased to normal level in 6-8 days and maintained for 6 weeks. Level of fasting C-peptide of these mice was higher compared to diabetic control mice (P=0.027). In WJ-MSCs prevention group, WJ-MSCs played a protective role for 8-week delayed onset of diabetes, and fasting C-peptide in this group was higher compared to the other two diabetic groups (P=0.013, 0.035). Compared with diabetic control group, frequencies of CD4+CD25+Foxp3+ Tregs in WJ-MSCs prevention group and treatment group were higher, while levels of IL-2, IFN-γ, and TNF-α were lower (P<0.001); the degree of insulitis was also depressed, especially for WJ-MSCs prevention group (P<0.05). Infusion of WJ-MSCs could aid in T1DM through regulation of the autoimmunity and recovery of islet ß-cells no matter before or after onset of T1DM. WJ-MSCs might be an effective method for T1DM.

Diabetes mellitus and poorer prognosis in hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: Previous studies suggested that diabetes mellitus was associated with cancer risk and prognosis, but studies investigating the relationship between diabetes mellitus and survival in patients with hepatocellular carcinoma (HCC) reported inconsistent findings. To derive a more precise estimate of the prognostic role of diabetes mellitus in HCC, we systematically reviewed published studies and carried out a meta-analysis. METHODS: Eligible articles were identified in electronic databases from their inception through September 16, 2013. To evaluate the correlation between diabetes mellitus and prognosis in HCC, the pooled hazard ratios (HR) and their 95% confidence intervals (95% CI) for poorer overall and disease-free survivals were calculated by standard meta-analysis techniques with fixed-effects or random-effects models. RESULTS: 21 studies with a total of 9,767 HCC patients stratifying overall survival and/or disease-free survival in HCC patients by diabetes mellitus status were eligible for meta-analysis. 20 studies with a total of 9,727 HCC cases investigated the overall survival, and 10 studies with a total of 2,412 HCC patients investigated the disease-free survival. The pooled HRs for overall survival and disease-free survival were 1.46 (95% CI, 1.29 to 1.66; P<0.001) and 1.57 (95% CI, 1.21 to 2.05; P = 0.001), respectively. The adjusted HRs for overall survival and disease-free survival were 1.55 (95% CI, 1.27 to 1.91; P<0.001) and 2.15 (95% CI, 1.75 to 2.63; P<0.001), respectively. In addition, for patients receiving hepatic resection, diabetes mellitus was associated with both poorer overall survival and poorer disease-free survival, and for patients receiving non-surgical treatment or patients receiving radiofrequency ablation, diabetes mellitus was associated with poorer overall survival. There was no evidence for publication bias. CONCLUSION: Diabetes mellitus is independently associated with both poorer overall survival and poorer disease-free survival in HCC patients.

Significant associations between X-ray repair cross-complementing group 3 genetic polymorphisms and thyroid cancer risk.

Polymorphisms in X-ray cross-complementing group 3 (XRCC3) are proposed to be associated with cancer susceptibility, but previous studies on the associations between XRCC3 polymorphisms and thyroid cancer are controversial. We performed a systemic review and meta-analysis to investigate the associations of XRCC3 polymorphisms with thyroid cancer risk. We used odds ratio (OR) with 95 % confidence interval (95%CI) to assess the associations. For XRCC3 C241T polymorphism, meta-analysis of total eligible studies showed that there was no association between XRCC3 C241T polymorphism and thyroid cancer risk, but subgroup analysis in Caucasians showed that there was a significant association between XRCC3 C241T polymorphism and thyroid cancer risk (T versus C: OR = 1.30, 95%CI 1.05-1.62, P = 0.01; TT versus CC: OR = 1.74, 95%CI 1.13-2.70, P = 0.01; TT versus CC/CT: OR = 1.74, 95%CI 1.16-2.60, P = 0.007). For XRCC3 A17893G polymorphism, meta-analysis of total eligible studies showed that there was an obvious association between XRCC3 A17893G polymorphism and thyroid cancer risk (GG versus AA/AG: OR = 0.57, 95%CI 0.35-0.93, P = 0.02), but subgroup analysis by ethnicity only identify the significant association in Asians. In summary, the meta-analysis suggests that there are significant associations of XRCC3 polymorphisms with thyroid cancer risk. Besides, more studies with large sample sizes are needed to further assess the associations above.

Association between TP53 Arg72Pro polymorphism and thyroid carcinoma risk.

TP53 Arg72Pro polymorphism has been proposed to have some effects on host's susceptibility to cancer. Several studies were published to assess the association between TP53 Arg72Pro polymorphism and thyroid carcinoma, but they reported controversial results. We performed a systemic review and meta-analysis to assess the association between TP53 Arg72Pro polymorphism and thyroid carcinoma. Odds ratio (OR) with 95% confidence interval (95% CI) was used to assess the association. Fourteen individual studies with 3,483 subjects were finally included into the meta-analysis. Overall, there was an obvious association between TP53 Arg72Pro polymorphism and thyroid carcinoma under the recessive model (ProPro vs. ArgArg/ArgPro, OR = 2.02, 95% CI 1.13 to 3.62, P = 0.02). Subgroup analysis by race showed that TP53 Arg72Pro polymorphism was associated with thyroid carcinoma in Caucasians (ProPro vs. ArgArg/ArgPro, OR = 2.31, 95% CI 1.08 to 4.93, P = 0.03). Subgroup analysis by histological type showed that TP53 Arg72Pro polymorphism was not associated with a risk of different types of thyroid carcinoma. In summary, the meta-analysis suggests that TP53 Arg72Pro polymorphism is associated with thyroid carcinoma risk in Caucasians. Besides, more studies with large sample size are needed to further assess the associations above.