The Role of PPARγ Gene Polymorphisms, Gut Microbiota in Type 2 Diabetes: Current Progress and Future Prospects.

Over the past decade, there has been a significant increase in studies investigating the relationship between the polymorphisms of the Peroxisome Proliferator-Activated Receptor gamma (PPARγ) gene and Type 2 Diabetes (T2D). PPARγ, a critical transcription factor, plays a central role in lipid metabolism, insulin resistance, and inflammatory response. Concurrently, the influence of gut microbiota on the development of T2D has gained increasing attention, especially their role in affecting host metabolism, such as lipid metabolism and the PPARγ signaling pathway. This review provides a comprehensive analysis of recent studies on PPARγ gene polymorphisms and their association with T2D, with a specific emphasis on the implications of gut microbiota and their interaction with PPARγ pathways. We also discuss the potential of manipulating gut microbiota and targeting PPARγ gene polymorphisms in T2D management. By deepening our understanding of these relationships, we aim to pave the way for novel preventative and therapeutic strategies for T2D.

[Effect of different suspension moxibustion methods on syndrome characteristics of rats with rheumatoid arthritis of heat bi syndrome based on "moxibustion can be used for heat syndrome"].

OBJECTIVE: To observe the effects of different suspension moxibustion methods on the syndrome characteristics and inflammatory factors of rats with rheumatoid arthritis (RA) of heat bi syndrome and to prove the concept of "moxibustion can be used for heat syndrome". METHODS: Among seventy Wistar rats, 12 rats were randomly selected as a normal group, and the remaining rats were induced by collagen combined with wind, dampness, and heat environmental stimulation to establish the RA model of heat bi syndrome. Forty-eight rats with successful model establishment were further randomly divided into a model group and three moxibustion groups (mild moxibustion group, rotating moxibustion group and sparrow-pecking moxibustion group), with 12 rats in each group. The acupoints "Quchi" (LI 11), "Dazhui" (GV 14) and ashi point were used in all moxibustion groups, with mild moxibustion, rotating moxibustion, and sparrow-pecking moxibustion intervention given respectively, each acupoint was treated with moxibustion for 10 min a day, and 6 days were considered one course of treatment, with a total of three courses. After the intervention, the arthritis index (AI), the Evans blue (EB) extravasated volume in the soft tissue of the right hind paw, and the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-10 in the serum were measured by ELISA in each group. The volume of the bilateral hind paw was measured; the infrared thermal imaging was collected to analyze the temperature of the plantar area of the bilateral foot pads, and the reaction time of plantar heat pain was calculated before and after modeling, as well as after the 1st, 2nd and 3rd courses of interrention. The ankle dorsiflexion angle of the right hind foot was also measured before and after modeling, as well as after the intervention. RESULTS: After modeling, compared with the normal group, the rats in the model group had more high-temperature areas in the bilateral hind limbs, abnormal AI score, abnormal bilateral hind paw volume, abnormal temperature of the plantar area of the bilateral foot pads, abnormal foot pain response time, abnormal right hind ankle dorsiflexion angle, abnormal right hind paw soft tissue EB extravasation, and abnormal serum TNF-α and IL-10 levels (P<0.01, P<0.05). After the intervention, compared with the model group, the rats in each moxibustion group had decreased or disappeared high-temperature areas in the bilateral hind limbs, EB extravasated volume in the soft tissue of the right hind paw was reduced (P<0.05), and the right ankle dorsiflexion angle was increased (P<0.05), serum level of TNF-α was reduced, and level of IL-10 increased (P<0.05); the AI scores in the mild moxibustion group and the sparrow-pecking moxibustion group was decreased (P<0.01, P<0.05). After the 1st, 2nd and 3rd courses of intervention, compared with the model group, the bilateral hind paw volume of rats in each moxibustion group was decreased (P<0.05, P<0.01), and plantar heat pain reaction time was increased (P<0.05). After the 2nd course and the 3rd course of intervention, the temperature of the right hind paw pad area was decreased in each moribustion group (P<0.05); after the 3rd courses of intervention, the temperature of the left hind paw pad area was decreased in the mild moxibustion group (P<0.05). CONCLUSION: Suspension moxibustion could adjust the serum levels of TNF-α and IL-10 to improve the syndrome characteristics of RA rats of heat bi syndrome, such as joint redness, swelling, heat, pain and activity restriction. The effect of mild moxibustion is the most prominent. The findings could provide scientific basis for "moxibustion can be used for heat syndrome".

Correlation of HMGB1, PON-1, MCP-1, and Periodontal P. gingivalis with Amniotic Fluid Fecal Dye.

BACKGROUND: This paper aims to investigate the correlation between high mobility group protein-1 (HMG-b1), antioxidant enzyme-1 (paraoxon-1, PON-1), monocyte chemoattractant protein-1 (monocyte chemoattractant protein-1, MCP-1), P. gingivalis, and MSAF. MATERIALS AND METHODS: The total sample size comprised of 73 cases in both groups. These patients were further subdivided into 2 groups: the MSAF group and the control group. 38 women were in the MSAF group and 35 women with term amniotic fluid serum were in the control group. The MSAF group was selected as a full-term singleton amniotic fluid fecal infection group. Clinical data were collected, and specimens were collected. Fecal staining of amniotic fluid and full-term amniotic fluid removes the placenta and umbilical cord blood. The expression of HMGB1 in the placenta was observed by immune-histochemical staining of MSAF and control groups. The content of PON-1 in cord blood was determined by ELISA. RESULTS: Correlation between maternal and neonatal clinical data and MSAF was done; MSAF group mean gestational age was 41.38 ± 1.40 weeks; control group mean gestational age was 39.20 ± 1.24 weeks. This study found no correlation between the birth weight, maternal age, sex, first/transmaternal, hyperthyroidism, hypothyroidism, and anemia between the MSAF and control group with nonsignificant P value (P > 0.05). However, the fatal age, gestational diabetes, gestational hypertension, umbilical cord abnormalities, placental abnormalities, and neonatal asphyxia factors were statistically different with a significant P value of <0.05 between both groups. HMGB1 and Periodontal P. gingivalis are mostly expressed in placental trophoblast, vascular endothelial cells, and amniotic epithelial and interstitial cells. After HE staining of 72 placentas by HE in MSAF and control, 6 had acute chorioamnionitis (5.1 control), 32 had chronic (23.9), 35 had abnormal placentas, and three in MSAF had chorionic columnar metaplasia. In immune-histochemistry experiments, the HMGB1 expression intensity of placental tissue was higher in the MSAF group (P < 0.05); however, the level of PON-1 was lower in the MSAF group as compared to the controls (P < 0.05). CONCLUSIONS: Gestational age and placental abnormalities are clinical high-risk factors for MSAF. HMGB1, PON-1, MCP-1, and Periodontal P. gingivalis may be involved in the development of MSAF, suggesting an oxidative/antioxidant imbalance with inflammation, and may be one of the mechanisms for MSAF development.

Effect of Gegen Qinlian Decoction on Hepatic Gluconeogenesis in ZDF Rats with Type 2 Diabetes Mellitus Based on the Farnesol X Receptor/Ceramide Signaling Pathway Regulating Mitochondrial Metabolism and Endoplasmic Reticulum Stress.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a kind of disorder of glucose and lipid metabolism with the main clinical manifestation of long-term higher blood glucose level than the normal value. Farnesol X receptor (FXR)/ceramide signaling pathway plays an important role in regulating cholesterol metabolism, lipid homeostasis, and the absorption of fat and vitamins in diet. Gegen Qinlian Decoction (GQD) is a classical herbal formula, which has a good clinical therapeutic effect on diabetes-related metabolic syndrome. OBJECTIVE: To investigate the effect of Gegen Qinlian Decoction (GQD) on hepatic gluconeogenesis in obese T2DM rats based on the FXR/ceramide signaling pathway regulating mitochondrial metabolism and endoplasmic reticulum stress (ERS). METHODS: ZDF (fa/fa) rats were fed with high-fat diet to establish the T2DM model; GQD was given to T2DM model rats by gavage; changes of the general state and body weight of rats were recorded; fasting blood glucose was detected; blood insulin, blood ceramide, glycosylated hemoglobin in blood, acetyl CoA in liver mitochondria, and bile salt lyase in intestinal tissue were detected by ELISA. The content of T-ß-MCA in blood was detected by LC-MS; the content of glycogen in liver tissue was detected by PAS staining; the expression of FXR, Sptlc2, and Smpd3 in ileum tissue, P-PERK, ATF6α, GRP78 BIP, and P-IRE1 in the liver, and CS and PC protein in liver mitochondria was detected by immunohistochemistry and western blot assay. The mRNA expression levels of FXR, Sptlc2, and Smpd3 in the ileum, PERK, ATF6α, GRP78 BIP, and IRE1 in the liver, and CS and PC in liver mitochondria were detected by qRT-PCR. RESULTS: GQD can improve the general state of T2DM rats, slow down their weight gain, reduce the levels of fasting blood glucose, fasting insulin, glycosylated hemoglobin, blood ceramide, bile salt hydrolase in intestinal tissue, and acetyl CoA in liver mitochondria of T2DM rats, and increase the contents of liver glycogen and T-ß-MCA in blood of T2DM rats. At the molecular level, GQD can inhibit the expression levels of FXR, Sptlc2, and Smpd3 in the ileum of T2DM rats and the protein and mRNA expression levels of oxidative stress-related factors in the liver. At the same time, GQD can increase the expression of CS and reduce the expression of PC in liver mitochondria of T2DM rats. CONCLUSION: GQD can inhibit the FXR/ceramide signaling pathway, regulate endoplasmic reticulum stress, enhance the CS activity of liver mitochondria, reduce the acetyl CoA level and PC activity of liver mitochondria, inhibit hepatic gluconeogenesis, protect islet ß-cells, and control blood glucose.

C/EBPα-mediated transcriptional activation of miR-134-5p entails KPNA3 inhibition and modulates focal hypoxic-ischemic brain damage in neonatal rats.

Hypoxic-ischemic brain damage (HIBD) is a frequent cause of mortality and neurological handicaps in infants and children worldwide. To understand better the pathogenesis and management of HIBD, we established a HIBD model by common carotid artery ligation followed by systemic hypoxia in neonatal rats, and in other studies induced neuronal death in rat pheochromocytoma (PC12) cells by 12 h of oxygen-glucose deprivation (OGD). The level of KPNA3 declined in rats following experimental HIBD and in PC12 cells following OGD. KPNA3 overexpression protected neonatal rats against HIBD and PC12 cells against OGD-induced cell death. KPNA3 demonstrated to be the target of miR-134-5p could be activated by the transcriptional factor CCAAT/enhancer binding protein alpha (C/EBPα). The expression of miR-134-5p and C/EBPα was elevated in rats following experimental HIBD and in PC12 cells following OGD. In the parallel experiments, C/EBPα knockdown and miR-134 inhibition protected against HIBD pathology in neonatal rats and against OGD-induced neuronal death in PC12 cells. These findings reveal that the C/EBPα/miR-134-5p/KPNA3 axis mediates hypoxic-ischemic brain damage and neuronal death, thus presenting a potential therapeutic target for the treatment of human newborns at risk for HIBD.

[Acupuncture Intervention Improves Behavior Reactions and Learning-memory Ability in Post-traumatic Stress Disorder Rats].

OBJECTIVE: To observe the therapeutic effect of acupuncture in the treatment of post-traumatic stress disorder (PTSD)-induced abnormal behavior reactions and learning-memory ability in rats with traumatic injury. METHODS: Sixty male SD rats were randomly divided into control, model, model＋animal capturing (capturing), medication and acupuncture groups (n＝12 rats in each). The PTSD model was established by "electric shock plus incarceration" method. Acupuncture was applied to "Baihui" (GV 20), and unilateral "Neiguan" (PC 6), "Shenmen" (HT 7) and "Taichong" (LR 3) once daily for 12 days. The rats in the medication group were treated by gavage of Paroxetine Hydrochloride solution (0.42 mg/mL), once daily for 12 days. The open field test containing horizontal (crossing grid lines) and rearing tests was performed for examining the rats' locomotor activity and anxiety-like behavior; and location navigation (escape latency) and special probe tests (platform quadrant crossing times) of Morris water maze tasks were detected for assessing the rats' learning-memory ability. On day 12 of the experiments, the rats were submitted to 3 consecutive sessions of open field tests for observing the time of familiar objects (TF) and the time of novelty object (TN) of exploration in 5 min (an object-location and an object-recognition tasks), followed by calculating the discrimination index [DI＝(TN－TF)/(TN＋TF)x100%]. RESULTS: After modeling, compared with the control group, the numbers of crossed grids and rearing, and DI were significantly decreased (P<0.05), while the number of fecal pellets and escape latency were significantly increased in both the model and capturing groups (P<0.05). After the intervention, the number of both crossed grids and rearing, platform quadrant crossing times, and DI were considerably increased (P<0.05), and the rats' escape latency and fecal pellet number were obviously decreased in both medication and acupuncture groups relevant to the model and capturing groups (P<0.05). No significant differences were found between the acupuncture and medication groups in the above mentioned 5 indexes (P>0.05)．. CONCLUSION: Acupuncture can effectively reduce anxiety-like behavior and improve the impaired learning-memory ability in PTSD rats.

[Progress of the Mechanism of Acupuncture to Promote Repair of Facial Nerve Injury].

Facial nerve injury results in facial muscle movement disorders that interferes with patient's life. Acupuncture is an effective therapy for facial nerve injury, but its mechanism has not been clarified. The evidence supports that acupuncture can accelerate the repair of facial nerve injury by adjusting the electric wave of patient's facial muscle, improving facial blood circulation, and promoting the expression of cell and protein molecule.

[Review on Modern Repair Mechanism of Moxibustion for Treating Inflammatory Damage of Rheumatoid Arthritis].

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Persistent inflammation of the synovial membrane is the main characteristic pathological symptom. Moxibustion for treating RA has achieved significant clinical effect in recent years. A large number of experimental studies have also shown that moxibustion promoted the repair of inflammatory damage induced by RA. Based on summarizing 10 years related literatures, the authors analyzed the repair mechanisms of moxibustion for inflammatory damage in RA from central mechanisms including glucocorticoid receptor, melatonine, hypothalamic-pituitary-adrenal axis, and cholinergic nerve to peripheral mechanisms including local inflammatory mediators, cytokine, and inflammatory cell signaling pathway, so as to provide evidences and reference for further research.

[Effect of insulin-like growth factor-1 on hyperoxia-induced apoptosis in A549 cells].

OBJECTIVE: To investigate the effect of insulin-like growth factor-1 (IGF-1), which can promote cell differentiation and inhibit cell apoptosis, on hyperoxia-induced apoptosis in A549 cells and its anti-apoptotic mechanism. METHODS: A549 cells were sub-cultured, exposed to hyperoxic conditions and were then treated with different concentrations of IGF-1 (1, 10, and 100 ng/mL) for 48 hours. Cell viability was measured by MTT assay. Cell apoptosis was evaluated by Annexin V-FITC/PI double-staining flow cytometry. Expression levels of Bax and Bcl-2 were measured by flow cytometry. RESULTS: The middle-dose and high-dose IGF-1 intervention groups had higher cell viabilities than the hyperoxic exposure group [(64±3)% and (88±4)% vs (51±3)%; P<0.05]. Compared with the air control group, the hyperoxic exposure group had a significantly higher apoptotic rate [(38.3±5.4)% vs (2.4±0.9)%; P<0.05], a significantly lower expression level of Bcl-2 [(72±5)% vs (91±4)%; P<0.05], and a significantly higher expression level of Bax [(54±6)% vs (3±2)%; P<0.05]. Compared with the hyperoxic exposure group, the low-dose, middle-dose, and high-dose IGF-1 intervention groups had significantly lower apoptotic rates [(16.1±4.7)%, (9.2±2.8)%, and (6.9±2.5)% vs (38.3±5.4)%; P<0.05], significantly higher expression level of Bcl-2 [(79±4)%, (94±4)%, and (100±5)% vs (72±5)%; P<0.05], and significantly lower expression level of Bax [(26±4)%, （5±2)%, and (4±2)% vs (54±6)%; P<0.05]. CONCLUSIONS: Hyperoxia significantly inhibits proliferation and promotes apoptosis in A549 cells. IGF-1 may promote cell proliferation and inhibit hyperoxia-induced apoptosis in A549 cells by regulating the expression of Bcl-2 and Bax.

[Experimental evaluation of cross section for Rb(5Dj)+H2-->rbH+H reaction].

The Rb(5Dj )+H2-->RbH[X 1sigma+(v"==0)]+H photochemical reaction was studied in a cell experiment applying a laser pump-absorption technique. Using two-photon excitation of the Rb5 (2)D atomic level in a Rb-H2 vapor mixture, the resulting fluorescence includes a direct component arising from the optically excited state and a sensitized component due to the collisionally populated fine-structure state. The RbH molecules are formed in three-body reactive collisions between excited Rb5 (2)D atoms and ground state H2 molecules. Near-infrared absorption band RbH X (1)sigma+ (v"==0-->v'==17) near 852 nm by using a diode laser was measured. The absorbed intensity of laser beam through a length L of the RbH vapor is defined as deltaI' and deltaI" where deltaI' and deltaI" are the absorbed intensity of pumping 5D(3/2) and 5D(5/2) levels, respectively. The ratio of deltaI' to deltaI" contains information on reactivity. w5D(3/2) and W5D(3/2) are the production rates of Rb in the 5D(5/2) and 5D(3/2) levels by direct laser excitation from the 5S(1/2) level. Using a second experiment in which pump laser is used to pump the 5D(3/2) and 5D(5/2) states in a pure Rb vapor (T = 290 K), and the i'/i" where i' and i" are measured intensities of the 5D(3/2)-->5P(1/2) and 5D(5/2)-->5P(3/2) transition, respectively, is determined. At low density of Rb atoms, the 5D mixing rate is neglect. The rate of 5D(3/2) and 5D(5/2) fluorescence yields the ratio of 5D(3/2) to 5D(5/2) pump production rate. The rate equations were solved, and the authors estimate the value of the cross section at T=385 K and P(H2) =400 Pa for collisional energy transfer from Rb5D(3/2) to 5D(5/2), from Rb(5D)to Rb states other than Rb(5D)to be 9.8 x 10(-16) cm2 and 2.0 x 10(-16) cm2, respectively. The reaction cross sections [i.e., Rb(5Dj)+H2-->RbH+H] for j being 3/2 and 5/2 are 5.4 x 10(-7) and 2.3 x 10(-17) cm2, respectively. The relative reactivity with H2 for two studied atoms is in an order of Rb(5D(3/2)>Rb(5D(5/2)), and this is consistent with the result obtained from a laser pump-probe technique.