Pattern of prefrontal cortical activation and network revealed by task-based and resting-state fNIRS in Parkinson’s disease’s patients with overactive bladder symptoms

BackgroundOveractive bladder (OAB) symptoms are common in Parkinson’s disease (PD), and negatively contribute to the quality of life (QoL) of patients. To explore the underlying pathophysiological mechanism, we investigated the correlation between the prefrontal cortex (PFC) function and OAB symptoms in PD patients.MethodsOne hundred fifty-five idiopathic PD patients were recruited and classified either as PD-OAB or PD-NOAB candidates based on their corresponding OAB symptom scores (OABSS). A linear regression analysis identified a correlative connection of cognitive domains. Then cortical activation during the performance of the verbal fluency test (VFT) and brain connectivity during resting state were conducted by functional near-infrared spectroscopy (fNIRS) for 10 patients in each group to investigate their frontal cortical activation and network pattern.ResultsIn cognitive function analysis, a higher OABS score was significantly correlated with a lower FAB score, MoCA total score, and sub-scores of visuospatial/executive, attention, and orientation as well. In the fNIRS study, the PD-OAB group exhibited significant activations in 5 channels over the left hemisphere, 4 over the right hemisphere, and 1 in the median during the VFT process. In contrast, only 1 channel over the right hemisphere showed significant activation in the PD-NOAB group. The PD-OAB group revealed hyperactivation, particularly in certain channel in the left dorsolateral prefrontal cortex (DLPFC), compared with PD-NOAB (FDR P < 0.05). In the resting state, there was a significant increase of the resting state functional connectivity (RSFC) strength between the bilateral Broca area, left frontopolar area (FPA-L) and right Broca’s area (Broca-R), between the FPA and Broca’s area if merging the bilateral regions of interest (ROI), and also between the two hemispheres in the PD-OAB group. The Spearman’s correlation confirmed that the OABS scores were positively correlated with RSFC strength between the bilateral Broca area, FPA-L and Broca-R, between the FPA and Broca area if merging the bilateral ROI.ConclusionIn this PD cohort, OAB was related to decreased PFC functions, with particularly hyperactivated left DLPFC during VTF and an enhanced neural connectivity between the two hemispheres in the resting state as observed by fNIRS imaging

Jia-Wei-Kai-Xin-San treatment alleviated mild cognitive impairment through anti-inflammatory and antiapoptotic mechanisms in SAMP8 mice

Background. Alleviating mild cognitive impairment (MCI) is crucial to delay the progression of Alzheimer’s disease (AD). Jia-Wei-Kai-Xin-San (JWKXS) is applied for treating AD with MCI. However, the mechanism of JWKXS in the treatment of MCI is unclear. Thus, this study aimed to investigate the effect and mechanism of JWKXS in SAMP8 mice models of MCI. Methods. MCI models were established to examine learning and memory ability and explore the pathomechanisms in brain of SAMP8 mice at 4, 6, and 8 months. The mice were treated for 8 weeks and the effects of JWKXS on MCI were characterized through Morris water maze and HE/Nissl’s/immunohistochemical staining. Its mechanism was predicted by the combination of UPLC-Q-TOF/MS and system pharmacology analysis, further verified with SAMP8 mice, BV2 microglial cells, and PC12 cells. Results. It was found that 4-month-old SAMP8 mice exhibited MCI. Two months of JWKXS treatment improved the learning and memory ability, alleviated the hippocampal tissue and neuron damage. Through network pharmacology, four key signaling pathways were found to be involved in treatment of MCI by JWKXS, including TLR4/NF-κB pathway, NLRP3 inflammasome activation, and intrinsic and extrinsic apoptosis. In vitro and in vivo experiments demonstrated that JWKXS attenuated neuroinflammation by inhibiting microglia activation, suppressing TLR4/NF-κB and NLRP3 inflammasome pathways, and blocking the extrinsic and intrinsic apoptotic pathways leading to neuronal apoptosis suppression in the hippocampus. Conclusion. JWKXS treatment improved the learning and memory ability and conferred neuroprotective effects against MCI by inducing anti-inflammation and antiapoptosis. Limitations. The small sample size and short duration of the intervention limit in-depth investigation of the mechanisms. Future Prospects. This provides a direction for further clarification of the anti-AD mechanism, and provides certain data support for the formulation to move toward clinical practice

Fluid inclusion study of the Gaofeng tin-polymetallic deposit in the Dachang ore field, Guangxi, China

The Dachang tin-polymetallic district, Guangxi, China, is one of the largest tin ore district in the world and contains the Lamo Zn-Cu proximal skarn deposit, the Tongkeng-Changpo and Gaofeng tin-base metal deposits, and the Huile and Dafulou black shale-hosted cassiterite-sulfide deposits. They are hosted by Devonian carbonate-rich sediments near the underlying Cretaceous (91 similar to 96Ma) Longxianggai granite. The Gaofeng deposit in the district occurs in the Middle Devonian reef limestone with higher grade ore and giant resource of Sn. The mineralization includes the early ore stage of cassiterite-arsenopyrite-pyrrhotite and the late ore stage of carbonate-sulfide-sulfosalt. Petrography, microthermometry, and Laser Raman spectroscopy, combined with scanning electron microscope-cathodoluminescence (SEM-CL) analyses of fluid inclusions are used to characterize the chemical evolution of ore fluids at the Gaofeng deposit. Two types of fluid inclusions are recognized in quartz and cassiterite : CO2-CH4 vapor-rich fluid inclusions are mainly observed in quartz and cassiterite associated with cassiterite-arsenopyrite-pyrrhotite stage and have high homogenization temperatures of 360 similar to 410 degrees C and salinities of 3% similar to 6% NaCleqv, whereas two-phase, liquid-rich aqueous fluid inclusions only occur in quartz related to sulfide-sulfosalt-carbonate stage and have relatively low homogenization temperatures ranging from 270 to 310 degrees C and salinities of 3% similar to 6% NaCleqv. The range of salinity for all fluid inclusions is similar to those of CO2 vapor-rich fluid inclusions (7% similar to 9% NaCleqv) in diopside and garnet in the Lamo skarn Zn-Cu deposit nearby the Gaofeng deposit. Oxygen and hydrogen isotopes of ore fluids from quartz and cassiterite indicate magmatic water in origin. Base on the physical and chemical evolution of ore fluids, it is concluded that the mineralizing fluids for the Gaofeng deposit were probably derived from intermediate density, supercritical single-phase fluid that exsolved from the deep crystallizing granite. This magmatic fluid reacted with carbonate-rich host rocks in the depth that led to phase segregation to form brine and vapor-like fluid. Vapor contraction and cooling of vapor-like fluids may deposit cassiterite and arsenopyrite, and followed by sulfides and sulfosalts at the Gaofeng deposit

Melatonin as a therapeutic agent for alleviating endothelial dysfunction in cardiovascular diseases: Emphasis on oxidative stress

The vascular endothelium is vital in maintaining cardiovascular health by regulating vascular permeability and tone, preventing thrombosis, and controlling vascular inflammation. However, when oxidative stress triggers endothelial dysfunction, it can lead to chronic cardiovascular diseases (CVDs). This happens due to oxidative stress-induced mitochondrial dysfunction, inflammatory responses, and reduced levels of nitric oxide. These factors cause damage to endothelial cells, leading to the acceleration of CVD progression. Melatonin, a natural antioxidant, has been shown to inhibit oxidative stress and stabilize endothelial function, providing cardiovascular protection. The clinical application of melatonin in the prevention and treatment of CVDs has received widespread attention. In this review, based on bibliometric studies, we first discussed the relationship between oxidative stress-induced endothelial dysfunction and CVDs, then summarized the role of melatonin in the treatment of atherosclerosis, hypertension, myocardial ischemia-reperfusion injury, and other CVDs. Finally, the potential clinical use of melatonin in the treatment of these diseases is discussed

Identification of Candidate Genes and Biosynthesis Pathways Related to Fertility Conversion by Wheat KTM3315A Transcriptome Profiling

The Aegilops kotschyi thermo-sensitive cytoplasmic male sterility (K-TCMS) system may facilitate hybrid wheat (Triticum aestivum L.) seed multiplication and production. The K-TCMS line is completely male sterile during the normal wheat-growing season, whereas its fertility can be restored in a high-temperature environment. To elucidate the molecular mechanisms responsible for male sterility/fertility conversion and candidate genes involved with pollen development in K-TCMS, we employed RNA-seq to sequence the transcriptomes of anthers from K-TCMS line KTM3315A during development under sterile and fertile conditions. We identified 16840 differentially expressed genes (DEGs) in different stages including15157 known genes (15135 nuclear genes and 22 plasmagenes) and 1683 novel genes. Bioinformatics analysis identified possible metabolic pathways involved with fertility based on KEGG pathway enrichment of the DEGs expressed in fertile and sterile plants. We found that most of the genes encoding key enzyme in the phenylpropanoid biosynthesis and jasmonate biosynthesis pathways were significant upregulated in uninucleate, binuclate or trinucleate stage, which both interact with MYB transcription factors, and that link between all play essential roles in fertility conversion. The relevant DEGs were verified by quantitative RT-PCR. Thus, we suggested that phenylpropanoid biosynthesis and jasmonate biosynthesis pathways were involved in fertility conversion of K-TCMS wheat. This will provide a new perspective and an effective foundation for the research of molecular mechanisms of fertility conversion of CMS wheat. Fertility conversion mechanism in thermo-sensitive cytoplasmic male sterile/fertile wheat involves the phenylpropanoid biosynthesis pathway, jasmonate biosynthesis pathway, and MYB transcription factors

Does an apple a day keep away diseases? Evidence and mechanism of action

Abstract Apples and their products exemplify the recently reemphasized link between dietary fruit intake and the alleviation of human disease. Their consumption does indeed improve human health due to their high phytochemical content. To identify potentially relevant articles from clinical trials, some epidemiological studies and meta‐analyses, and in vitro and in vivo studies (cell cultures and animal models), PubMed was searched from January 1, 2012, to May 15, 2022. This review summarized the potential effects of apple and apple products (juices, puree, pomace, dried apples, extracts rich in apple bioactives and single apple bioactives) on health. Apples and apple products have protective effects against cardiovascular diseases, cancer, as well as mild cognitive impairment and promote hair growth, healing of burn wounds, improve the oral environment, prevent niacin‐induced skin flushing, promote the relief of UV‐induced skin pigmentation, and improve the symptoms of atopic dermatitis as well as cedar hay fever among others. These effects are associated with various mechanisms, such as vascular endothelial protection, blood lipids lowering, anti‐inflammatory, antioxidant, antiapoptotic, anti‐invasion, and antimetastatic effects. Meanwhile, it has provided an important reference for the application and development of medicine, nutrition, and other fields

Sodium Danshensu stabilizes atherosclerotic vulnerable plaques by targeting IKKβ mediated inflammation in macrophages

Background: The primary cause of acute cardiovascular events with high mortality is the rupture of atherosclerotic plaque followed by thrombosis. Sodium Danshensu (SDSS) has shown potential in inhibiting the inflammatory response in macrophages and preventing early plaque formation in atherosclerotic mice. However, the specific targets and detailed mechanism of action of SDSS are still unclear. Objective: This study aims to investigate the efficacy and mechanism of SDSS in inhibiting inflammation in macrophages and stabilizing vulnerable plaques in atherosclerosis (AS). Materials and Methods: The efficacy of SDSS in stabilizing vulnerable plaques was demonstrated using various techniques such as ultrasound, Oil Red O staining, HE staining, Masson staining, immunohistochemistry, and lipid analysis in ApoE-/- mice. Subsequently, IKKβ was identified as a potential target of SDSS through protein microarray, network pharmacology analysis, and molecular docking. Additionally, ELISA, RT-qPCR, Western blotting, and immunofluorescence were employed to measure the levels of inflammatory cytokines, IKKβ, and NF-κB pathway-related targets, thereby confirming the mechanism of SDSS in treating AS both in vivo and in vitro. Finally, the impact of SDSS was observed in the presence of an IKKβ-specific inhibitor. Results: Initially, the administration of SDSS led to a decrease in the formation and area of aortic plaque, while also stabilizing vulnerable plaques in ApoE-/- mice. Furthermore, it was identified that IKKβ serves as the primary binding target of SDSS. Additionally, both in vivo and in vitro experiments demonstrated that SDSS effectively inhibits the NF-κB pathway by targeting IKKβ. Lastly, the combined use of the IKKβ-specific inhibitor IMD-0354 further enhanced the beneficial effects of SDSS. Conclusions: SDSS stabilized vulnerable plaques and suppressed inflammatory responses by inhibiting the NF-κB pathway through its targeting of IKKβ

Dysregulation of PAK1 Is Associated with DNA Damage and Is of Prognostic Importance in Primary Esophageal Small Cell Carcinoma

Primary esophageal small cell carcinoma (PESCC) is a rare, but fatal subtype of esophageal carcinoma. No effective therapeutic regimen for it. P21-activated kinase 1 (PAK1) is known to function as an integrator and an indispensable node of major growth factor signaling and the molecular therapy targeting PAK1 has been clinical in pipeline. We thus set to examine the expression and clinical impact of PAK1 in PESCC. The expression of PAK1 was detected in a semi-quantitative manner by performing immunohistochemistry. PAK1 was overexpressed in 22 of 34 PESCC tumors, but in only 2 of 18 adjacent non-cancerous tissues. Overexpression of PAK1 was significantly associated with tumor location (p = 0.011), lymph node metastasis (p = 0.026) and patient survival (p = 0.032). We also investigated the association of PAK1 with DNA damage, a driven cause for malignancy progression. γH2AX, a DNA damage marker, was detectable in 18 of 24 (75.0%) cases, and PAK1 expression was associated with γH2AX (p = 0.027). Together, PAK1 is important in metastasis and progression of PESCC. The contribution of PAK1 to clinical outcomes may be involved in its regulating DNA damage pathway. Further studies are worth determining the potentials of PAK1 as prognostic indicator and therapeutic target for PESCC

Anti-Hyperglycemic Effects of Refined Fractions from <i>Cyclocarya paliurus</i> Leaves on Streptozotocin-Induced Diabetic Mice

To identify the chemical components responsible for the anti-hyperglycemic effect of Cyclocarya paliurus (Batal.) Iljinsk (Juglandaceae) leaves, an ethanol extract (CPE) and a water extract (CPW) of C. paliurus leaves, as well as their total flavonoids (CPF), triterpenoids (CPT) and crude polysaccharides (CPP), were prepared and assessed on streptozotocin (STZ)-induced diabetic mice. After being orally administrated once a day for 24 days, CPF (300 mg/kg), CPP (180 mg/kg), or CPF+CPP (300 mg/kg CPF + 180 mg/kg CPP) treatment reversed STZ-induced body weight and muscle mass losses. The glucose tolerance tests and insulin tolerance tests suggested that CPF, CPP, and CPF+CPP showed anti-hyperglycemic effect in STZ-induced diabetic mice. Furthermore, CPF enhances glucose-stimulated insulin secretion in MIN6 cells and insulin-stimulated glucose uptake in C2C12 myotubes. CPF and CPP suppressed inflammatory cytokine levels in STZ-induced diabetic mice. Additionally, CPF and CPP improved STZ-induced diabetic nephropathy assessed by H&E staining, blood urea nitrogen content, and urine creatinine level. The molecular networking and Emperor analysis results indicated that CPF showed potential anti-hyperglycemic effects, and HPLC–MS/MS analysis indicated that CPF contains 3 phenolic acids and 9 flavonoids. In contrast, CPT (650 mg/kg) and CPC (300 mg/kg CPF + 180 mg/kg CPP + 650 mg/kg CPT) did not show anti-hyperglycemic effect. Taken together, polysaccharides and flavonoids are responsible for the anti-hyperglycemic effect of C. paliurus leaves, and the clinical application of C. paliurus need to be refined