Association between neck circumference and bone mineral loss: A cross-sectional study in Sichuan province in China.

BACKGROUND: The associations of fat distribution with bone health are debatable. We aimed to investigate the associations between neck circumference (NC) and bone mineral loss among the adult Chinese population in Sichuan province. METHODS: We examined overall NC size and NC stratums (≤35 cm, 3538 cm) with bone mineral density (BMD) at the femoral neck, lumbar spine, total hip skeletal sites in 135 men and 479 women respectively, and assessed whether adiposity, lipids, and calcium and phosphorus levels, might have a biased role in the relationship of NC and bone mineral loss with linear regression, logistic regression, and restricted cubic spline models. RESULTS: The overall NC size is not independently associated with BMD at all sites. However, stratification for NC revealed that the positive correlation between NC and BMD at all sites were significant in the NC stratum 1 (≤35 cm) in women (all p < 0.05) and NC stratum 2 (3538 cm) compared with NC stratum 1 using logistic regression. However, in women, no statistically significant association was observed between NC stratum 1 and BMD values after adjustment for the same confounders. CONCLUSIONS: Our findings suggest a NC stratum-specific association between NC size and bone mineral loss in men in Sichuan province in China, but not in women.

Effect of Bifidobacterium on osteoclasts: TNF-α/NF-κB inflammatory signal pathway-mediated mechanism.

Osteoporosis is a systemic multifactorial bone disease characterized by low bone quality and density and bone microstructure damage, increasing bone fragility and fracture vulnerability. Increased osteoclast differentiation and activity are important factors contributing to bone loss, which is a common pathological manifestation of bone diseases such as osteoporosis. TNF-a/NF-κB is an inflammatory signaling pathway with a key regulatory role in regulating osteoclast formation, and the classical pathway RANKL/RANK/OPG assists osteoclast formation. Activation of this inflammatory pathway promotes the formation of osteoclasts and accelerates the process of osteoporosis. Recent studies and emerging evidence have consistently demonstrated the potential of probiotics to modulate bone health. Secretions of Bifidobacterium, a genus of probiotic bacteria in the phylum Actinobacteria, such as short-chain fatty acids, equol, and exopolysaccharides, have indicated beneficial effects on bone health. This review discusses the molecular mechanisms of the TNF-a/NF-κB inflammatory pathway in regulating osteoclast formation and describes the secretions produced by Bifidobacterium and their potential effects on bone health through this pathway, opening up new directions for future research.

Efficacy of intranasal insulin in improving cognition in mild cognitive impairment or dementia: a systematic review and meta-analysis.

Background: Insulin regulates many aspects of brain function related to mild cognitive impairment (MCI) or dementia, which can be delivered to the brain center via intranasal (IN) devices. Some small, single-site studies indicated that intranasal insulin can enhance memory in patients with MCI or dementia. The pathophysiology of Alzheimer's disease (AD) and diabetes mellitus (DM) overlap, making insulin an attractive therapy for people suffering from MCI or dementia. Objective: The goal of the study is to evaluate the effectiveness of IN insulin on cognition in patients with MCI or dementia. Methods: We searched the electronic database for randomized controlled trials (RCTs) that verified the effects of insulin on patients with MCI or dementia.16 studies (899 patients) were identified. Results: The pooled standard mean difference (SMD) showed no significant difference between IN insulin and placebo groups; however, statistical results suggested a difference between study groups in the effects of ADCS-ADL; AD patients with APOE4 (-) also showed improved performance in verbal memory; other cognitions did not improve significantly. Conclusion: In view of IN insulin's promising potential, more researches should be conducted at a larger dose after proper selection of insulin types and patients. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022353546.

Corrigendum: Efficacy of resveratrol supplementation on glucose and lipid metabolism: A meta-analysis and systematic review.

[This corrects the article DOI: 10.3389/fphys.2022.795980.].

Multiple roles of ghrelin in breast cancer.

Breast cancer is one of the most threatening malignant tumors in women worldwide; hence, investigators are continually performing novel research in this field. However, an accurate prediction of its prognosis and postoperative recovery remains difficult. The severity of breast cancer is patient-specific and affected by several health factors; thus, unknown mechanisms may affect its progression. This article analyzes existing literature on breast cancer, ranging from the discovery of ghrelin to its present use, and aims to provide a reference for future research into breast cancer mechanisms and treatment-plan improvement. Various parts of ghrelin have been associated with breast cancer by direct or indirect evidence. The ghrelin system may encompass the direction of expanding breast cancer treatment methods and prognostic indicators. Therefore, we compiled almost all studies on the relationship between the ghrelin system and breast cancer, including unacylated ghrelin, its GHRL gene, ghrelin O-acyltransferase, the receptor growth hormone secretagogue receptor, and several splice variants of ghrelin to lay the foundation for future research.

Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review.

Background: Lipids are ubiquitous metabolites with diverse functions. Excessive lipid accumulation can trigger lipid redistribution among metabolic organs such as adipose, liver and muscle, thus altering the lipid metabolism. It has been revealed that disturbed lipid metabolism would cause multiple disease complications and is highly correlated with human morbidity. Resveratrol (RSV), a phytoestrogen with antioxidant, can modulate insulin resistance and lipid profile. Recently, research on RSV supplementation to improve glucose and lipid metabolism has been controversial. A meta-analysis may provide a scientific reference for the relationship between lipid metabolism and RSV supplementation. Methods and Analysis: We searched the PubMed, Cochrane Library, Web of Science, and Embase databases from inception to October 2021 using relevant keywords. A comprehensive search for randomized controlled trials (RCTs) was performed. For calculating pooled effects, continuous data were pooled by mean difference (MD) and 95% confidence interval (CI). Adopting the method of inverse-variance with a random-effect, all related statistical analyses were performed using the Rev Man V.5.3 and STATA V.15 software. Results: A total of 25 articles were incorporated into the final meta-analysis after removal of duplicates by checking titles and abstracts and excluding non-relevant articles. The selected articles had a total of 1,171 participants, including 578 in the placebo group and 593 in the intervention group. According to the current meta-analysis, which demonstrated that there was a significant decrease in waist circumference (SMD = -0.36; 95% CI: -0.59, -0.14; P = 0.002; I 2 = 88%), hemoglobin A1c (-0.48; -0.69, -0.27; P ≤ 0.001; I 2 = 94%), total cholesterol (-0.15; -0.3, -0.01; P = 0.003; I 2 = 94%), low density lipoprotein cholesterol (-0.42; -0.57, -0.27; P ≤ 0.001; I 2 = 92%), high density lipoprotein cholesterol (0.16; -0.31, -0.02; P = 0.03; I 2 = 81%) following resveratrol administration. Conclusion: These results suggest that RSV has a dramatic impact on regulating lipid and glucose metabolism, and the major clinical value of resveratrol intake is for obese and diabetic patients. We hope that this study could provide more options for clinicians using RSV. Furthermore, in the future, large-scale and well-designed trials will be warranted to confirm these results. Systematic Review Registration: Website [https://www.crd.york.ac.uk/prospero/#recordDetails], identifier [CRD42021244904].

Effects of electroacupuncture on bladder dysfunction and the expression of PACAP38 in a diabetic rat model.

Objective: To explore the effects and the possible mechanism of electroacupuncture (EA) on diabetic bladder dysfunction (DBD) in streptozotocin-high fat diet (STZ-HFD) induced type 2 diabetes mellitus (T2DM) rats. Methods: The experiment was divided into Control, diabetic bladder dysfunction, electroacupuncture, and Sham electroacupuncture group. After 8 weeks of electroacupuncture intervention, the body mass, 24 h urine volume, intraperitoneal glucose tolerance test (IPGTT), and urodynamics were detected. After the wet weight of the bladder was detected, the hematoxylin-eosin (HE), Masson's trichrome, and TUNEL were used to analyze histological changes. The PACAP38 expressions in the bladder were detected by Real-time PCR and Western blot. Results: Compared to the Control group, the bladder wet weight, 24 h urine volume, blood glucose, maximum bladder capacity, bladder compliance, bladder wall thickness, the smooth muscle/collagen ratio, and apoptosis rate of the diabetic bladder dysfunction group were significantly increased. Moreover, the body mass and leak point pressure were significantly reduced. Compared with the Sham electroacupuncture group, the bladder wet weight, maximum bladder capacity, bladder compliance, bladder wall thickness, and apoptosis rate of the electroacupuncture group were significantly reduced. In contrast, the leak point pressure was increased. The PACAP38 mRNA and PACAP38 protein expression of the diabetic bladder dysfunction group were significantly lower than the Control group, while electroacupuncture treatment could upregulate PACAP38 mRNA levels and PACAP38 protein expression of diabetic bladder dysfunction model rats. Conclusion: electroacupuncture could ameliorate bladder dysfunction in the diabetic bladder dysfunction model rats by reversing bladder remodeling, which might be mainly mediated by regulating the PACAP38 level.

Protective Effect of Keluoxin against Diabetic Nephropathy in Type 2 Diabetic Mellitus Models.

Diabetic nephropathy (DN) is a chronic kidney disease that develops in patients with diabetes mellitus (DM). Renal dysfunction and persistent proteinuria are the main clinical features of DN. Podocyte injury is an important cause of persistent proteinuria and diabetic kidney disease (DKD) progression. Traditional Chinese patent medicines can improve renal function by enhancing autophagy and promoting apoptosis. Keluoxin is a Chinese patent medicine that has the effect of invigorating qi and nourishing yin, activating blood, and eliminating blood stasis. Therefore, we hypothesized that Keluoxin may have a protective effect against diabetic nephropathy in rats with type 2 DM. Rats induced with diabetes through streptozocin (STZ) injection and a high-fat and high-sugar diet were treated with Keluoxin (0.63 g/kg/day) for 8 weeks, and renal function, biochemical indicators, and histopathological changes in renal tissues were observed. Immunofluorescence staining and western blot analysis were used to detect the expression of autophagy-related proteins. The results showed that Keluoxin reduced blood glucose and lipid levels, improved renal function, and alleviated renal histopathological changes in rats with DN. The therapeutic effect was similar to that of Irbesartan (15.6 mg/kg/day). It is inferred that the mechanism works through reducing the obstruction of downstream pathways of autophagy by improving the lysosomal degradation function and alleviating podocyte injury. This study demonstrates that Keluoxin could regulate autophagy in podocytes, alleviate kidney injury in rats with DN, and have a protective effect on renal function; its mechanism can thus be a potential therapy for DN.

Effect of Electroacupuncture on Bladder Dysfunction via Regulation of MLC and MLCK Phosphorylation in a Rat Model of Type 2 Diabetes Mellitus.

Previous studies observed have reported that electroacupuncture (EA) is effective in relieving diabetic bladder dysfunction (DBD); however, little is known about the mechanism. Therefore, we explored the effects and mechanisms of EA on DBD in streptozotocin-high-fat diet- (STZ-HFD-) induced diabetic rats. The Sprague-Dawley male rats were divided randomly into four groups: normal group, diabetes mellitus group (DM group), DM with EA treatment group (EA group), and DM with sham EA treatment group (sham EA group). After 8 weeks of EA treatment, the body weight, serum glucose, bladder weight, and cystometrogram were evaluated. The bladder wall thickness was examined by abdominal ultrasound imaging. After the transabdominal ultrasound measurements, hematoxylin-eosin (HE) staining was used to observe the bladder mucosa layer. The bladder detrusor smooth muscle cells (SMCs) and fibroblasts were observed under transmission electron microscopy (TEM). The phospho-myosin light chain (p-MLC), phospho-myosin light chain kinase (p-MLCK), and phospho-myosin phosphatase target subunit 1 (p-MYPT1) levels in the bladder were examined using Western blot. The bladder weight, serum glucose, bladder wall thickness, volume threshold for micturition, and postvoid residual (PVR) volume in the diabetic rats were significantly higher than those in the control animals. EA treatment significantly reduced the bladder weight, bladder wall thickness, volume threshold for micturition, and PVR volume in diabetic rats. EA caused a significant increase in the MLC dephosphorylation and MLCK phosphorylation levels in the group compared to the sham EA and model groups. EA reduced the infiltration of inflammatory cells in the bladder mucosa layer of diabetic rats. In addition, EA repaired the damaged bladder detrusor muscle of diabetic rats by reducing mitochondrial damage of the SMCs and fibroblasts. Therefore, EA could reduce the bladder hypertrophy to ameliorate DBD by reversing the impairment in the mucosa layer and detrusor SMCs, which might be mainly mediated by the regulation of p-MLC and p-MLCK levels.

The mechanism of electroacupuncture for depression on basic research: a systematic review.

BACKGROUND: Electroacupuncture (EA) is generally accepted as a safe and harmless treatment option for alleviating depression. However, there are several challenges related to the use of EA. Although EA has been shown to be effective in treating depression, the molecular mechanism is unclear. OBJECTIVE: To reveal the therapeutic effect of EA and its possible mechanism in the treatment of depression. SEARCH STRATEGY: We performed a systematic search according to PRISMA guidelines. We electronically searched PubMed, Web of Science (WOS), the China National Knowledge Infrastructure (CNKI), Wanfang Data Information Site and the VIP information database for animal studies in English published from the inception of these databases to December 31, 2019. INCLUSION CRITERIA: Electronic searches of PubMed, WOS, the CNKI, Wanfang and the VIP database were conducted using the following search terms: (depression OR depressive disorder OR antidepressive), (rat OR mouse) AND (acupuncture OR EA). DATA EXTRACTION AND ANALYSIS: The data were extracted primarily by one author, and a follow-up review was conducted by the other authors. RESULTS: Twenty-eight articles met the inclusion criteria. The most commonly used method for inducing depression in animal models was 21 days of chronic unpredictable mild stress. For the depression model, the most commonly selected EA frequency was 2 Hz. Among the 28 selected studies, 11 studies observed depression-related behaviors and used them as indicators of EA efficacy. The other 17 studies focused on mechanisms and assessed the indexes that exhibited abnormalities that were known to result from depression and then returned to a normal range after EA treatment. Treatment of depression by EA involves multiple therapeutic mechanisms, including inhibition of HPA axis hyperactivity and inflammation, regulation of neuropeptides and neurotransmitters, modulation of the expression of particular genes, restoration of hippocampal synaptic plasticity, increased expression of BDNF, and regulation of several signaling pathways. CONCLUSIONS: This review reveals that the mechanisms underlying the effect of acupuncture involve multiple pathways and targets, suggesting that acupuncture is a wholistic treatment for people rather than for diseases. Our findings also explain why acupuncture can treat various disorders in addition to depression.

The effect of Sancai powder on glycemic variability of type 2 diabetes in the elderly: A randomized controlled trial.

BACKGROUND: Type 2 diabetes is a kind of metabolic disease. Its clinical characteristic is hyperglycemia. Recently, more and more elderly people suffer from type 2 diabetes, and the glycemic variability of the elderly is greater. In addition, blood sugar variation is more likely to cause diabetes complications than simple hyperglycemia. Sancai podwer (SC) is based on the theory of traditional Chinese medicine and gradually formed in the summary of clinical experience. It has the effect of lowering blood sugar and alleviating clinical symptoms of diabetes. But the existing evidence of its efficacy on glycemic variability is insufficient. So, in our study, the randomized controlled trials will be used as a research method to explore the effects of SC on glycemic variability of type 2 diabetes. METHOD: We will use randomized controlled experiments based on the recommended diagnostic criteria, inclusion and exclusion criteria. A total of 60 elderly patients with type 2 diabetes will be randomly divided into treatment group and control group, 30 cases in each group. The control group will receive conventional western medicine and the intervention group will receive SC combined with western medicine. The standard deviation and coefficient of variation of blood glucose level will be used as evaluation indexes. DISCUSSION: This study can provide evidence for the clinical efficacy and safety of SC in elderly patients with type 2 diabetes mellitus. TRIAL REGISTRATION: This study is registered on the Chinese Clinical Trial Registry: ChiCTR2000032611.

Vitamin D supplementation for nonalcoholic fatty liver disease in type 2 diabetes mellitus: A protocol for a systematic review and meta-analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM), and low vitamin D levels are positively associated with NAFLD and T2DM. But there is absence of convincing evidence-based medicine to confirm the efficacy of vitamin D supplementation for T2DM with NAFLD. Thus, we aimed to conduct this meta-analysis to summarize the efficacy of vitamin D supplementation for T2DM combined with NAFLD, and help to further clarify its beneficial action on diabetic patients with NAFLD. METHODS: The study only selects clinical randomized controlled trials of vitamin D supplementation for T2DM combined with NAFLD. We will search each database from the built-in until July 2020. The English literature mainly searches Cochrane Library, Pubmed, EMBASE, and Web of Science. While the Chinese literature comes from CNKI, CBM, VIP, and Wangfang database. Meanwhile, we will retrieve clinical trial registries and grey literature. Two researchers worked independently on literature selection, data extraction, and quality assessment. The dichotomous data is represented by relative risk (RR), and the continuous is expressed by mean difference (MD) or standard mean difference (SMD), eventually the data is synthesized using a fixed effect model (FEM) or a random effect model (REM) depending on the heterogeneity. The imaging markers of liver, biomarkers of hepatic steatosis, serological indexes of hepatic fibrosis, serum NAFLD liver fat score were evaluated as the main outcomes. While several secondary outcomes were also evaluated in this study. The statistical analysis of this meta-analysis was conducted by RevMan software version 5.3. RESULTS: This meta-analysis will further determine the beneficial efficacy of vitamin D supplementation for T2DM combined with NAFLD. CONCLUSION: This study determines the positive efficacy of vitamin D supplementation for diabetic patients with NAFLD.

Effect of electroacupuncture on diabetic neurogenic bladder: A randomized controlled trial protocol.

BACKGROUND: The most common and bothersome lower urinary tract complication of diabetes mellitus is diabetic neurogenic bladder (DNB). Acupuncture has certain advantages in treating bladder dysfunction including urinary retention and incontinence. Therefore, we think that electroacupuncture (EA) may be beneficial to DNB patients. However, it is not clear whether EA combined with basic western medicine could optimize the therapeutic effect for DNB. METHOD/DESIGN: This is a sham-controlled, patient-blinded, pioneer randomized controlled trial (RCT). One hundred fifty eligible patients will be randomly divided into 3 groups: A. basic western medicine (BWC), B. EA with BWC, C. sham EA with BWC. EA treatment will be given twice a week for 12 weeks at bilateral BL23, BL32, BL33, and BL35. The BWC group will received Alpha-lipoic acid (ALA) and methylcobalamin (MC) treatment for 12 weeks, 2 treatment sessions per week. The primary outcome is scored by the 72-hour bladder diary (72h-BD). The secondary outcomes will be scored by the American Urological Association symptom index (AUA-SI), Post-void residual urine volume (PVR) and urodynamic tests. All the assessments will be conducted at baseline and the 12th weeks after the intervention starts. The follow-up assessments will be performed with 72h-BD and AUA-SI in the 4th, 12th, and 24th weeks after intervention ends. DISCUSSION: This trial protocol provides an example of the clinical application acupuncture treatment in the management of DNB. This RCT will provide us information on the effect of treating DNB patients with only acupuncture, western medicine therapy (ALA + MC) as well as the combination of both. The additive effect or synergistic effect of acupuncture and basic western medicine will then be analyzed. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000030421.

Electroacupuncture restores hippocampal synaptic plasticity via modulation of 5-HT receptors in a rat model of depression.

OBJECTIVE: The study aimed to determine the effect of electroacupuncture (EA) on Wistar Kyoto (WKY) depressive model rats and explore the possible mechanism of EA on hippocampal CA1 region neuronal synaptic plasticity. METHODS: The male WKY rats were randomized to three experimental groups (EA, Sham EA, and Model group, n = 8/group), and Wistar rats as the normal control group (n = 8). EA treatment was administered once daily for 3 weeks at acupuncture points Baihui (GV20) and Yintang (EX-HN3). In the Sham EA group, acupuncture needles were inserted superficially into the acupoints without electrical stimulation. On day 21, the forced swimming test (FST), open field test (OFT) and sucrose preference test (SPT) were conducted. After the behavioral tests, long-term potentiation (LTP) was evoked at Schaffer collateral-CA1 synapses in hippocampal slices in vitro by electrophysiological recording, 5-HTT, 5-HT1A and 5-HT1 B protein levels in the hippocampus CA1 region were examined by using Western blot. RESULT: EA significantly decreased immobility in FST and improved sucrose intake compared with the Sham EA and Model groups. The center time and total move time in OFT were significantly increased in the EA group compared to the Model group. Compared with those of the Sham EA and Model groups, the fEPSP slope of the EA group increased significantly, and the LTP induction was successful. EA significantly decreased 5-HTT protein expression in the hippocampus CA1 region in comparison to the Sham EA and Model groups. Additionally, EA down regulated the 5-HT1A protein expression in the hippocampus CA1 region in comparison to the Sham EA group. CONCLUSION: EA could ameliorate depressive-like behaviors by restoring hippocampus CA1 synaptic plasticity, which might be mainly mediated by regulating 5-HT receptor levels.