Impact of Combined Nifedipine and Aspirin Therapy on Hemodynamics in Patients with Early Eclampsia.

Background: Preeclampsia poses substantial risks during pregnancy. Exploring innovative treatment approaches like the combination of Nifedipine and aspirin is crucial for improving maternal and fetal outcomes. Objective: This study aims to assess the efficacy of nifedipine and aspirin tablets in treating preeclampsia and their impact on blood rheology and coagulation. Methods: We selected 96 pregnant patients with preeclampsia treated at our hospital between January 2020 and January 2022. The patients were randomly assigned to either the research group (n=48) or the control group (n=48). Nifedipine was administered to the control group, while the research group received a combination of Nifedipine and aspirin. We compared the overall treatment effectiveness and the incidence of unfavorable pregnancy outcomes between the two groups. Results: The research group exhibited a significantly higher overall treatment effectiveness rate (93.75%) compared to the control group (P < .05). After treatment, levels of fibrinogen (FIB), whole high-cut blood viscosity (HBV), whole low-cut blood viscosity (LBV), plasma viscosity (PV), and erythrocyte rigidity index (HGX) were significantly lower in the study group than in the control group (P < .05). Additionally, plasminogen time (PT) and activated partial thromboplastin time (APTT) were higher in the research group compared to the control group (P < .05). The research group also experienced a lower frequency of negative pregnancy outcomes (4.17%) in contrast to the control group (18.75%) (P < .05). Conclusions: The nifedipine and aspirin combination effectively treats pregnancy hypertension, enhancing both coagulation and hemorheology for improved maternal and fetal health outcomes.

Severe inflammation in new-borns induces long-term cognitive impairment by activation of IL-1ß/KCC2 signaling during early development.

BACKGROUND: Neonatal sepsis can induce long-term cognitive impairment in adolescence or adulthood, but the underlying molecular mechanism is not fully understood. The expression of K+-Cl- co-transporter 2 (KCC2) plays a pivotal role in the GABAergic shift from depolarizing to hyperpolarizing during early postnatal development. In this study, we aimed to determine whether neonatal severe inflammation-induced cognitive impairment was associated with the expression of KCC2 during early development. METHODS: Neonatal severe inflammation was established by intraperitoneal injection of high dose lipopolysaccharide (LPS, 1 mg kg-1) in postnatal day 3 (P3) rats. The Morris water maze task and fear conditioning test were used to investigate long-term cognitive functions. ELISA, RT-PCR and Western blotting were used to examine the expression levels of proinflammatory cytokines and KCC2. Perforated patch-clamping recordings were used to determine the GABAergic shift. RESULTS: Neonatal severe inflammation led to long-term cognitive impairment in rats. Meanwhile, sustained elevation of interleukin-1 beta (IL-1ß) levels was found in the hippocampus until P30 after LPS injection. Elevated expression of KCC2 and hyperpolarized GABA reversal potential (EGABA) were observed in CA1 hippocampal pyramidal neurons from the P7-P10 and P14-P16 rats after LPS injection. Specific knockdown of IL-1ß mRNA expression rescued the elevated expression of KCC2 and the hyperpolarized EGABA at P7-P10 and P14-P16. Accordingly, specific knockdown of IL-1ß or KCC2 expression improved the cognitive impairment induced by neonatal severe inflammation. CONCLUSIONS: Sustained elevation of IL-1ß in the hippocampus may induce cognitive impairment by upregulation of KCC2 during early development.

Effect of thyrotropin suppressive therapy on lumbar bone mineral density in patients with differentiated thyroid cancer: a retrospective cohort study.

Background: To investigate the effect of thyrotropin (TSH) suppressive therapy on lumbar bone mineral density (BMD) in patients with differentiated thyroid cancer (DTC) after operation. Methods: We retrospectively analyzed 70 DTC patients at intermediate or high risk of recurrence, including 17 males, 30 premenopausal females, and 23 postmenopausal females. All patients were treated with oral 131I to clear any residual thyroid and L-thyroxine tablets to suppress TSH after surgery. The baseline and follow-up lumbar BMD were measured. The anthropometric and biochemical parameters, the doses of calcium supplement, and levothyroxine were collected. Results: Lumbar BMD in the postmenopausal female group was markedly decreased (regression coefficient: -0.201; P<0.001) compared to the male group and premenopausal female group (both: P>0.05). Further comparisons between groups found that premenopausal women had a monthly lumbar BMD reduction of 0.001 g/cm2 more than men, but the difference was not statistically significant (P=0.515). In contrast, postmenopausal women had a monthly lumbar BMD reduction of 0.004 g/cm2 more than men and 0.003 g/cm2 more than postmenopausal controls (P=0.017 and P<0.001, respectively). Lumbar BMD decreased significantly with the increasing duration of TSH suppression in both the calcium supplement group and the non-calcium supplement group (both: P<0.05), but there was no statistical difference between the two groups (P=0.534). Conclusions: The longer the duration of TSH suppression in DTC patients after operation, the more significant the decrease of BMD, especially in postmenopausal women. Furthermore, calcium supplementation did not significantly improve lumbar BMD.

Salvianolic acid A relieves cognitive disorder after chronic cerebral ischemia: Involvement of Drd2/Cryab/NF-κB pathway.

Chronic cerebral ischemia (CCI) refers to long-term hypoperfusion of cerebral blood flow with the main clinical manifestations of progressive cognitive impairment. The pathological mechanism of CCI is complex, and there is a lack of effective treatments. Salvianolic acid A (SalA) is a neuroprotective extract of Salvia miltiorrhiza with the effects of anti-inflammation and anti-apoptosis. In this study, the effect of SalA on cognitive function and Drd2/Cryab/NF-κB signaling pathway in rats with CCI was investigated. Morris water maze and open field test were used to observe the effects of SalA on the cognitive function of CCI rats. The pathological changes in the brain were observed by HE, Nissl, and LFB staining. TUNEL staining, enzyme-linked immunosorbent assay, and western blot analysis were used to detect the inflammatory and apoptosis in the cortex and hippocampus. The expression of Drd2/Cryab/NF-κB pathway-related molecules and Drd2 localization were detected by western blotting and dual immunofluorescence, respectively. SH-SY5Y cells were exposed to chronic hypoglycemic and hypoxic injury in vitro, and Drd2 inhibitor haloperidol was used to verify the involved pathway. The results showed that SalA could improve the cognitive function of CCI rats, reduce pathological damage of cortex and hippocampus, inhibit neuroinflammation and apoptosis, and suppress the activation of NF-κB by regulating Drd2/Cryab pathway. And SalA inhibited NF-κB activation and nuclear translocation in SH-SY5Y cells by upregulating Drd2/Cryab pathway, which was reversed by haloperidol interference. In conclusion, SalA could relieve CCI-induced cognitive impairment in rats, at least partly through the Drd2/Cryab/NF-κB pathway.

Xiao-Xu-Ming decoction prevented hemorrhagic transformation induced by acute hyperglycemia through inhibiting AGE-RAGE-mediated neuroinflammation.

Stroke is one of the leading causes of death worldwide. Hemorrhagic transformation (HT) is a common serious complication of ischemic stroke (IS) and is related to poor prognosis. Hyperglycemia after stroke is associated with the occurrence of HT and seriously affects the clinical treatment of stroke. Our previous experiments demonstrated that the Xiao-Xu-Ming decoction effective components group (XXMD), which is a Chinese medicine formula reconstituted by active ingredients, has multiple pharmacological effects in the treatment of IS. However, the effects of XXMD on HT after IS remain unclear. Thus, we investigated the preventive effects of XXMD on hyperglycemia-induced HT and further explored the underlying mechanism. Acute hyperglycemia combined with the electrocoagulation cerebral ischemia model was used to establish the HT model. XXMD (37.5, 75, 150 mg/kg/d) was given by gavage for 5 days. Network pharmacology was used to predict potential targets and pathways of XXMD in HT occurrence, and further studies confirmed the related targets. The results showed that hyperglycemia aggravated neurological deficits and blood-brain barrier (BBB) disruption, leading to intracerebral hemorrhage. Pretreatment with XXMD improved neurological function and BBB integrity and inhibited HT occurrence. Network pharmacology revealed that AGE-RAGE-mediated neuroinflammation may be associated with hyperglycemia-induced HT. Further studies confirmed that hyperglycemia activated the AGE-RAGE signaling pathway, increased the expression of HMGB1, TLR4 and p-p65, and induced the release of inflammatory factors and neutrophil infiltration, leading to HT. XXMD could inhibit AGE-RAGE-mediated neuroinflammation. These findings indicated that pretreatment with XXMD alleviated hyperglycemia-induced HT, which may be associated with the inhibition of AGE-RAGE-mediated neuroinflammation. Therefore, XXMD may be a potential therapeutic drug for HT.

Finger Citron Extract Ameliorates Glycolipid Metabolism and Inflammation by Regulating GLP-1 Secretion via TGR5 Receptors in Obese Rats.

Finger citron (FC) is one of many traditional Chinese herbs that have been used to treat obesity. The aim of this study was to elucidate the pharmacological effects and mechanisms of FC on obese rats. Rats were fed with a high-fat diet as a model of obesity and treated with FC at three different dosages for 6 weeks. Pathology in liver tissue was observed. Glucose levels, lipids levels, and inflammatory indicators in serum were evaluated by enzyme-linked immunosorbent assay. Furthermore, the expression of G protein-coupled receptor 5 (TGR5) pathway genes in rat colon tissue was detected by reverse transcription-polymerase chain reaction analysis (RT-PCR). Our result revealed that FC alleviates obesity by reducing body weight (BW) and waist circumference, managing inflammation and improving glycolipid metabolism, liver function, and liver lipid peroxidation in vivo. In addition, the mechanism of FC on obesity is possibly the stimulation of glucagon-like peptide-1 (GLP-1) secretion by activating the TGR5 pathway in intestinal endocrine cells. Our studies highlight the obesity reduction effects of FC and one of the mechanisms may be the activation of the TGR5 pathway in intestinal endocrine cells.

Astragaloside IV reverses simvastatin-induced skeletal muscle injury by activating the AMPK-PGC-1α signalling pathway.

In this study, we investigated the effect of astragaloside IV on skeletal muscle energy metabolism disorder caused by statins and explored the possible mechanisms. High-fat diet-fed apolipoprotein E knockout (ApoE-/- ) mice performed aerobic exercise and were administered simvastatin, simvastatin + trimetazidine, or simvastatin + astragaloside IV by gavage. At the end of treatment, exercise performance was assessed by the hanging grid test, forelimb grip test, and running tolerance test. Moreover, plasma lipid and creatine kinase concentrations were measured. After sacrifice, the gastrocnemius muscle was used to assess muscle morphology, and energy metabolism was evaluated by determining the concentration of lactic acid and the storage capacity of adenosine triphosphate and glycogen. Mitochondrial function was assessed by measuring mitochondrial complex III and citrate synthase activity and membrane potential. In addition, oxidative stress was assessed by determining the level of hydrogen peroxide. Finally, using western blotting and reverse transcription polymerase chain reaction, we explored the mechanism of astragaloside IV in alleviating simvastatin-induced muscle injury. Our results demonstrated that astragaloside IV reversed simvastatin-induced muscle injury without affecting the lipid-lowering effect of simvastatin. Moreover, astragaloside IV promoted the phosphorylation of AMPK and activated PGC-1α, which upregulated the expression of NRF1 to enhance energy metabolism and inhibit skeletal muscle cell apoptosis.

Sulfated Cyclocarya paliurus polysaccharides markedly attenuates inflammation and oxidative damage in lipopolysaccharide-treated macrophage cells and mice.

Natural polysaccharides and their modified derivatives are crucial supplements to the prevention of inflammation. This study aimed to evaluate the effect of sulfated modification on the anti-inflammatory and anti-oxidative activities of Cyclocarya paliurus polysaccharides (CP). A sulfated CP, S-CP1-4 was obtained using chlorosulfonic acid-pyridine method. The chemical components and FT-IR spectrum confirmed that sulfated group was synthesized to the polysaccharide chains successfully. S-CP1-4 was found to inhibit nitric oxide production, phagocytic activity and the release of interleukin (IL)-6 and IL-1ß in lipopolysaccharide-treated macrophage cells, RAW 264.7. S-CP1-4 significantly decreased the secretion of IL-6 and TNF-α and the thymus and spleen indexes, and increased the production of IL-10 in lipopolysaccharide-treated mice. S-CP1-4 could better protect the liver by inhibiting the activities of alanine aminotransferase and aspartate aminotransferase, and malondialdehyde level while increasing the superoxide dismutase activity and total anti-oxidative capacity. These results suggested that S-CP1-4 may be an effective anti-inflammatory agent, and sulfated modification may be a reliable method for the development of food supplements.

Zika Virus Replicons for Drug Discovery.

The current epidemic of Zika virus (ZIKV) has underscored the urgency to establish experimental systems for studying viral replication and pathogenesis, and countermeasure development. Here we report two ZIKV replicon systems: a luciferase replicon that can differentiate between viral translation and RNA synthesis; and a stable luciferase replicon carrying cell line that can be used to screen and characterize inhibitors of viral replication. The transient replicon was used to evaluate the effect of an NS5 polymerase mutation on viral RNA synthesis and to analyze a known ZIKV inhibitor. The replicon cell line was developed into a 96-well format for antiviral testing. Compare with virus infection-based assay, the replicon cell line allows antiviral screening without using infectious virus. Collectively, the replicon systems have provided critical tools for both basic and translational research.

An Infectious cDNA Clone of Zika Virus to Study Viral Virulence, Mosquito Transmission, and Antiviral Inhibitors.

The Asian lineage of Zika virus (ZIKV) has recently caused epidemics and severe disease. Unraveling the mechanisms causing increased viral transmissibility and disease severity requires experimental systems. We report an infectious cDNA clone of ZIKV that was generated using a clinical isolate of the Asian lineage. The cDNA clone-derived RNA is infectious in cells, generating recombinant ZIKV. The recombinant virus is virulent in established ZIKV mouse models, leading to neurological signs relevant to human disease. Additionally, recombinant ZIKV is infectious for Aedes aegypti and thus provides a means to examine virus transmission. The infectious cDNA clone was further used to generate a luciferase ZIKV that exhibited sensitivity to a panflavivirus inhibitor, highlighting its potential utility for antiviral screening. This ZIKV reverse genetic system, together with mouse and mosquito infection models, may help identify viral determinants of human virulence and mosquito transmission as well as inform vaccine and therapeutic strategies.