Diabetes and osteoporosis: a two-sample mendelian randomization study.

BACKGROUND: The effects on bone mineral density (BMD)/fracture between type 1 (T1D) and type 2 (T2D) diabetes are unknown. Therefore, we aimed to investigate the causal relationship between the two types of diabetes and BMD/fracture using a Mendelian randomization (MR) design. METHODS: A two-sample MR study was conducted to examine the causal relationship between diabetes and BMD/fracture, with three phenotypes (T1D, T2D, and glycosylated hemoglobin [HbA1c]) of diabetes as exposures and five phenotypes (femoral neck BMD [FN-BMD], lumbar spine BMD [LS-BMD], heel-BMD, total body BMD [TB-BMD], and fracture) as outcomes, combining MR-Egger, weighted median, simple mode, and inverse variance weighted (IVW) sensitivity assessments. Additionally, horizontal pleiotropy was evaluated and corrected using the residual sum and outlier approaches. RESULTS: The IVW method showed that genetically predicted T1D was negatively associated with TB-BMD (ß = -0.018, 95% CI: -0.030, -0.006), while T2D was positively associated with FN-BMD (ß = 0.033, 95% CI: 0.003, 0.062), heel-BMD (ß = 0.018, 95% CI: 0.006, 0.031), and TB-BMD (ß = 0.050, 95% CI: 0.022, 0.079). Further, HbA1c was not associated with the five outcomes (ß ranged from - 0.012 to 0.075). CONCLUSIONS: Our results showed that T1D and T2D have different effects on BMD at the genetic level. BMD decreased in patients with T1D and increased in those with T2D. These findings highlight the complex interplay between diabetes and bone health, suggesting potential age-specific effects and genetic influences. To better understand the mechanisms of bone metabolism in patients with diabetes, further longitudinal studies are required to explain BMD changes in different types of diabetes.

Effects of mitochondrial dysfunction on bone metabolism and related diseases: a scientometric study from 2003 to 2022.

BACKGROUND: In recent years, mitochondrial dysfunction has been extensively studied and published, but research on the effects of mitochondrial dysfunction on bone metabolism and related diseases is only just beginning. Furthermore, no studies have been carried out to systematically illustrate this area from a scientometric point of view. The goal of this research is to review existing knowledge and identify new trends and possible hotspots in this area. METHODS: All publications related to the relationship between mitochondrial dysfunction and bone metabolism and related diseases from 2003 to 2022 were searched at the Web of Science Core Collection (WoSCC) on May 7, 2022. Four different analytical tools: VOSviewer 1.6.18, CiteSpace V 6.1, HistorCite (12.03.07), and Excel 2021 were used for the scientometric research. RESULTS: The final analysis included 555 valid records in total. Journal of Biological Chemistry (Co-citations = 916) is the most famous journal in this field. China (Percentage = 37%), the United States (Percentage = 24%), and Korea (Percentage = 12%) are the most productive countries. Blanco FJ and Choi EM are the main researchers with significant academic influence. Current research hotspots are basic research on mitochondrial dysfunction and the prevention or treatment of bone metabolism-related diseases. CONCLUSION: The study of the consequences of mitochondrial dysfunction on bone metabolism and associated diseases is advancing rapidly. Several prominent researchers have published extensive literature and are widely cited. Future research in this area will focus on oxidative stress, aging, gene expression, and the pathogenesis of bone metabolism-related diseases.

[Rehmanniae Radix and Rehmanniae Radix Praeparata improve diabetes induced by high-fat diet coupled with streptozotocin in mice through AMPK-mediated NF-κB/NLRP3 signaling pathway].

This study investigated the differential mechanisms of Rehmanniae Radix and Rehmanniae Radix Praeparata in improving diabetes in mice through AMPK-mediated NF-κB/NLRP3 signaling pathway. The diabetic mouse model was established with high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days), after which the mice were randomly divided into model group, low-dose(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-dose(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, catalpol group(250 mg·kg~(-1)), 5-hydroxymethylfurfural(5-HMF) group(250 mg·kg~(-1)), metformin group(250 mg·kg~(-1)), with the normal group also set. The organ indexes of heart,liver, spleen, lung, kidney and pancreas were calculated after four weeks of administration. The pathological changes and fibrosis of pancreas, kidney and liver in mice were observed by hematoxylin-eosin(HE) staining and Masson staining. Western blot was used to determine the expression levels of Toll-like receptor-4(TLR4), nuclear factor-κB(NF-κB), Nod-like receptor protein 3(NLRP3),interleukin-1ß(IL-1ß), adenosine monophosphate-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK) in the pancreas, kidney and liver of mice. Compared with the model group, the administration groups witnessed significant decrease in the liver,spleen, kidney, pancreas and fat indexes of diabetic mice, and there was no significant difference in heart and lung indexes. The pathological states and fibrosis of pancreatic, kidney and liver tissues were significantly improved after administration. Additionally, the expression levels of TLR4, NF-κB and NLRP3 in pancreas, kidney and liver of diabetic mice were significantly lowered. The expression levels of p-AMPK/AMPK were enhanced significantly in kidney and liver of mice in Rehmanniae Radix group while in pancreas, kidney and liver in Rehmanniae Radix Praeparata group. This suggests that Rehmanniae Radix and Rehmanniae Radix Praeparata differ in the mechanism of regulating energy metabolism of multiple organs and thereby exerting anti-inflammatory effects to alleviate symptoms of diabetic mice.

Anti-inflammatory and antioxidant effects of MOK, a polyherbal extract, on lipopolysaccharide­stimulated RAW 264.7 macrophages.

MOK, a pharmacopuncture medicine consisting of 10 herbs, has a long history as treatment for various inflammatory conditions. To investigate the mechanisms of action of MOK, its anti­inflammatory and antioxidative effects were assessed in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). RAW 264.7 cells were treated with different concentrations of MOK extract for 30 min prior to stimulation with or without LPS for the indicated times. Nitric oxide (NO) production was measured using Griess reagent, while the mRNA levels of inflammatory cytokines, tumor necrosis factor (TNF)­α, interleukin (IL)­1ß, IL­6 and the antioxidant enzymes Mn superoxide dismutase and heme oxygenase­1, were determined using reverse transcription­polymerase chain reaction analysis. Western blotting was used to determine the protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)­2, superoxide dismutase (SOD)2, catalase (CAT) and heme oxygenase­1 (HO­1), and the phosphorylation of mitogen­activated protein kinases (MAPKs), including ERK1/2, JNK and p38. Western blotting and immunocytochemistry were used to observe the nuclear expression of nuclear factor (NF)­κB p65. Additionally, reactive oxygen species (ROS) and prostaglandin (PG)E2 production were determined using the ROS assay and an enzyme immunoassay. With MOK treatment, there was a notable decrease in NO and PGE2 production induced by LPS in RAW 264.7 cells by downregulation of iNOS and COX­2 mRNA and protein expression. Furthermore, with MOK treatment, there was a decrease in the mRNA expression levels of TNF­α, IL­1ß and IL­6, as well as in the phosphorylation of ERK, JNK and p38 MAPK, by blocking the nuclear translocation of NF­κB p65 in LPS­stimulated cells. In addition, MOK treatment led to an increase in the antioxidant enzymes SOD, CAT and HO­1 in LPS­stimulated cells, with a concomitant decrease in ROS generation. These results indicate that the inflammatory responses in activated macrophages are inhibited by MOK through downregulation of the transcription levels of inflammatory mediators and inhibition of the MAPK/NF­κB pathway. Moreover, MOK protects against oxidative damage by upregulating the expression of antioxidant enzymes and generating ROS scavengers.

Therapeutic effects of acupuncture with MOK, a polyherbal medicine, on PTU-induced hypothyroidism in rats.

Acupuncture with MOK, a polyherbal medicine (MOK pharmacopuncture), has been used for the treatment of thyroid syndromes including hypothyroidism and hyperthyroidism in traditional Korean medicine. The present study investigated the effect of MOK pharmacopuncture on hypothyroidism and the mechanism underlying its antioxidation and immune regulation effects. Hypothyroidism was induced in Sprague-Dawley rats by subcutaneous injection of Propylthiouracil (PTU; 10 mg/kg) once daily for 4 weeks. MOK was administered by acupuncture on the acupoints around the thyroid gland of PTU-induced hypothyroidism rats once daily for 2 weeks following hypothyroidism induction. Administration of MOK pharmacopuncture significantly increased the PTU-induced decrease in body temperature of hypothyroidism rats. The weights of the spleen were also significantly decreased in hyperthyroidism rats following MOK pharmacopuncture. MOK pharmacopuncture significantly decreased the thyroid stimulating hormone level and increased the T3 and T4 levels in hypothyroidism rats. Administration of MOK pharmacopuncture significantly increased the glucose levels and decreased the levels of triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and alanine transaminase in the sera of hypothyroidism rats. The expression of transient receptor potential cation channel subfamily V member 1 was increased in dorsal root ganglion and brain tissues by administration of MOK pharmacopuncture, and glutathione levels and the expression of superoxide dismutase 1 and catalase were increased in the liver and brain tissues. Administration of MOK pharmacopuncture significantly inhibited interferon-γ expression and increased the expression of interleukin (IL)-4, IL-10, and Forkhead Box P3 in the spleen tissues of hypothyroidism rats. In histological analysis, the administration of MOK pharmacopuncture improved the pathological features in the thyroid glands of hypothyroidism rats. The results suggested that the administration of pharmacopuncture may ameliorate the pathological progression of hypothyroidism by multiple actions, including normalization of the hypothyroidism-induced thyroid hormone imbalance, stimulation of the antioxidant defense system, and regulation of the T helper (Th)1/Th2 imbalance. Therefore, MOK extract may be used for the treatment of hypothyroidism in Korean clinics as a useful pharmacopuncture medicine.

Processing of calamine with modern analytical techniques: Processed with Huanglian Decoction () and Sanhuang Decoction ().

OBJECTIVE: To determine the pyrolysis characteristics of calcined and processed calamine, qualitatively and quantitatively compare the contents of related elements, morphology and functional groups of the pyrolysis products dried at different heating temperatures and explore the critical temperature and the optimal drying temperature for the process of calamine with Huanglian Decoction (HLD, ) and San Huang Decoction (SHD, ). METHODS: Pyrolysis products were prepared by programmable and constantly heating the calcined and processed calamine to or at different heating temperatures. Thermogravimetry (TG) was used to test their pyrolysis characteristics. Fourier transform infrared spectroscopy and scanning electron microscopeenergy dispersive spectrometer were used to determine their morphology, functional groups and element contents. Page model was used to investigate the constant drying kinetics of processed calamine. RESULTS: The adding of HLD or SHD to calcined calamine (CC) can slow its weight loss in drying pyrolysis process. The temperature ranges where HLD and SHD can affect its weight loss were 65-150 °C and 74-180 °C, respectively. The drying temperature was optimized as 90 °C. The drying kinetic for the processed calamine fits Page model shows good linearity. CONCLUSIONS: Conclusions: The critical temperature and the optimal drying temperature where HLD and SHD can affect the weight loss rate in the process of calamine were explored using the theories and methods of both biophysical chemistry and processing of Chinese materia medica. This work provides a good example for the study of the process of other Chinese medicines using modern analytical techniques.

[Effect of Esculentoside A on Expression of AQP2 and AQP4 Protein of Kidney in Water-Loaded Rats].

OBJECTIVE: To observe the regulatory effect of Esculentoside A (EsA) on urination and the expression of AQP2 and AQP4 protein of kidney in water-loaded rats, and to discuss its mechanism of diuresis. METHODS: 50 male SD rats were randomly divided into five groups, including blank control group, hydrochlorothiazide group (0.4 mg/kg) and EsA high, middle and low dose groups (5.2, 2.6 and 1.3 mg/kg, respectively). After intraperitoneally injecting of different concentrations of EsA, urinary amount of model rats in continuous six hours was measured. Then the expression of AQP2 and AQP4 protein and mRNA of kidney were detected by immunohistochemistry method and Real-Time quantitative PCR. RESULTS: Compared with blank control group, the expression of AQP2 and AQP4 protein and mRNA of kidney were significantly reduced as well as the urinary amount was significantly increased in EsA high dose group (P < 0.05), while the expression of AQP2, AQP4 protein and mRNA of kidney as well as urinary amount had no obvious difference in EsA middle and low dose groups. CONCLUSION: 5.2 mg/kg of EsA can reduce the expression of AQP2 and AQP4 protein and mRNA of kidney and the reabsorption of water, which results in diuresis.

[Study on thermoanalysis-based calamina processing].

Thermogravimetry (TG), TG-MS, Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM)-energy dispersive spectrometer(EDS) were adopted to investigate the pyrolysis characteristics of calamina. According to the findings of the qualitative and quantitative studies on the changes in the content of relevant elements, the whole shape, the functional groups, and the volatile components of calamina before and after being pyrolyzed, the 200-360, 580-750 degrees C were two sensitive temperature ranges related to the changes in effective component during calamina processing. Thermal weight loss was observed for ZnCO3, Zn(OH)2 and ZnCO3-2Zn(OH)2-H2O under 200-360 degrees C and for CaCO3 under 580-750 degrees C. The results of studies on chemical reaction kinetics showed good linear relations. This experiment integrated relevant methods and theories of physical chemistry and science of traditional Chinese medicine processing, and interpretes calamina processing techniques and mechanism, in order to provide a good example for modem studies on other traditional Chinese medicine processing.