Transgenic female mice producing trans 10, cis 12-conjugated linoleic acid present excessive prostaglandin E2, adrenaline, corticosterone, glucagon, and FGF21.

Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully established to determine the anti-obesity properties of t10c12-CLA in male mice that could produce endogenous t10c12-CLA. To test whether there is a different impact of t10c12-CLA on lipid metabolism in both sexes, this study investigated the adiposity and metabolic profiles of female Pai mice that exhibited a dose-dependent expression of foreign Pai gene and a shift of t10c12-CLA content in tested tissues. Compared to their gender-match wild-type littermates, Pai mice had no fat reduction but exhibited enhanced lipolysis and thermogenesis by phosphorylated hormone-sensitive lipase and up-regulating uncoupling proteins in brown adipose tissue. Simultaneously, Pai mice showed hepatic steatosis and hypertriglyceridemia by decreasing gene expression involved in lipid and glucose metabolism. Further investigations revealed that t10c10-CLA induced excessive prostaglandin E2, adrenaline, corticosterone, glucagon and inflammatory factors in a dose-dependent manner, resulting in less heat release and oxygen consumption in Pai mice. Moreover, fibroblast growth factor 21 overproduction only in monoallelic Pai/wt mice indicates that it was sensitive to low doses of t10c12-CLA. These results suggest that chronic t10c12-CLA has system-wide effects on female health via synergistic actions of various hormones.

Rising Incidence of Acute Epiglottitis in Eastern China: An Eight-Year Retrospective Study and Its Association with the 24 Solar Terms.

Purpose: This study aimed to investigate the clinical characteristics of acute epiglottitis (AE) patients in East China and examine the correlation between the incidence of AE and the 24 solar terms (24 STs). Methods: A retrospective, observational study was conducted on patients diagnosed with AE between January 2014 and December 2021 at a single-center medical institution in East China. The clinical characteristics of patients with AE and their correlation with the 24 STs were investigated. Results: A total of 287 patients with AE were included in this study, among which there were 179 males (62.37%) and 108 females (37.63%), with a mean age of 47.79 ± 13.83 years (range 16-87 years). Of these patients, 100 (34.84%) had at least one comorbidity and the most common comorbidities were hypertension, smoking and type 2 diabetes. The duration of hospitalization was 3 days (IQR, 1-16 days). All patients, except for one who required tracheal intubation, were cured with intravenous antibiotic administration and the combined use of corticosteroids. The incidence of AE showed significant fluctuations between the 24 STs and the highest number of cases occurred during the Summer solstice (24 cases, 8.36%). Conclusion: The incidence of AE was seen to increase annually in this study. The main features of AE are sore throat, dysphagia, odynophagia and fever, which may be accompanied by inflammation in surrounding areas. A clear correlation exists between the incidence of AE and the fluctuations within the 24 STs, notably with the peak incidence observed during the Summer solstice, which approximately corresponds to June 21 to July 7 in the Gregorian calendar.

Study on Characteristics of Ultrasound-Assisted Fracture Splitting for AISI 1045 Quenched and Tempered Steel.

Ultrasonic vibration-assisted con-rod fracture splitting (UV-CFS) was used to carry out the fracture experiment of 1045 quenched and tempered steel. The effect of ultrasonic vibration on the fracture properties was studied, the fracture microstructure and the evolution of dislocations near the fracture were analyzed and the microscopic mechanism was analyzed. The results show that in the case of conventional fracture splitting without amplitude, the dimple and the fracture belong to ductile fracture. With the increase in ultrasonic amplitude, the plasticity and pore deformation of the con-rod samples decrease at first and then increase; when the amplitude reaches a certain point, the load required for cracking is reduced to a minimum and the ultrasonic hardening effect is dominant, resulting in a decrease in the plasticity of the sample, a cleavage fracture, a brittle fracture, the minimum pore deformation and high cracking quality. The research results also show that with the increase in ultrasonic amplitude, the fracture dislocation density decreases at first, then increases, and dislocation entanglement and grain breakage appear, then decrease, and multiple dislocation slip trajectories appear. The changes in the dislocation density and microstructure are consistent with the above results.

Material basis and molecular mechanisms of Chaihuang Qingyi Huoxue Granule in the treatment of acute pancreatitis based on network pharmacology and molecular docking-based strategy.

Objectives: This study aimed to analyze active compounds and signaling pathways of CH applying network pharmacology methods, and to additionally verify the molecular mechanism of CH in treating AP. Materials and methods: Network pharmacology and molecular docking were firstly used to identify the active components of CH and its potential targets in the treatment of AP. The pancreaticobiliary duct was retrogradely injected with sodium taurocholate (3.5%) to create an acute pancreatitis (AP) model in rats. Histological examination, enzyme-linked immunosorbent assay, Western blot and TUNEL staining were used to determine the pathway and mechanism of action of CH in AP. Results: Network pharmacological analysis identified 168 active compounds and 276 target proteins. In addition, there were 2060 targets associated with AP, and CH had 177 targets in common with AP. These shared targets, including STAT3, IL6, MYC, CDKN1A, AKT1, MAPK1, MAPK3, MAPK14, HSP90AA1, HIF1A, ESR1, TP53, FOS, and RELA, were recognized as core targets. Furthermore, we filtered out 5252 entries from the Gene Ontology(GO) and 186 signaling pathways from the Kyoto Encyclopedia of Genes and Genomes(KEGG). Enrichment and network analyses of protein-protein interactions predicted that CH significantly affected the PI3K/AKT signaling pathway, which played a critical role in programmed cell death. The core components and key targets showed strong binding activity based on molecular docking results. Subsequently, experimental validation demonstrated that CH inhibited the phosphorylation of PI3K and AKT in pancreatic tissues, promoted the apoptosis of pancreatic acinar cells, and further alleviated inflammation and histopathological damage to the pancreas in AP rats. Conclusion: Apoptosis of pancreatic acinar cells can be enhanced and the inflammatory response can be reduced through the modulation of the PI3K/AKT signaling pathway, resulting in the amelioration of pancreatic disease.

Trailblazing in Adjuvant Research: Succinate's Uncharted Territory with Neutrophils.

The purpose of this study is to investigate the previously unknown connection that succinate has with neutrophils in the setting of adjuvant-mediated immunological enhancement. It has been discovered that succinates stimulate the recruitment of neutrophils in immunization sites, which in turn induces the expression of what is known as neutrophil-derived B cell-activating factor (BAFF). Further amplification of vaccine-induced antibody responses is provided via the SUCNR1-IRF5-BAFF signaling pathway, which provides insights into a unique mechanism for immunological enhancement.

Mfn2 regulates mitochondria and mitochondria-associated endoplasmic reticulum membrane function in neurodegeneration induced by repeated sevoflurane exposure.

Repeated sevoflurane exposure in neonatal mice can leads to neuronal apoptosis and mitochondrial dysfunction. The mitochondria are responsible for energy production to maintain homeostasis in the central nervous system. The mitochondria-associated endoplasmic reticulum membrane (MAM) is located between the mitochondria and endoplasmic reticulum (ER), and it is critical for mitochondrial function and cell survival. MAM malfunction contributes to neurodegeneration, however, whether it is involved in sevoflurane-induced neurotoxicity remains unknown. Our study demonstrated that repeated sevoflurane exposure induced mitochondrial dysfunction and dampened the MAM structure. The upregulated ER-mitochondria tethering enhanced Ca2+ transition from the cytosol to the mitochondria. Overload of mitochondrial Ca2+ contributed to opening of the mitochondrial permeability transition pore (mPTP), which caused neuronal apoptosis. Mitofusin 2(Mfn2), a key regulator of ER-mitochondria contacts, was found to be suppressed after repeated sevoflurane exposure, while restoration of Mfn2 expression alleviated cognitive dysfunction due to repeated sevoflurane exposure in the adult mice. These evidences suggest that sevoflurane-induced MAM malfunction is vulnerable to Mfn2 suppression, and the enhanced ER-mitochondria contacts promotes mitochondrial Ca2+ overload, contributing to mPTP opening and neuronal apoptosis. This paper sheds light on a novel mechanism of sevoflurane-induced neurotoxicity. Furthermore, targeting Mfn2-mediated regulation of the MAM structure and mitochondrial function may provide a therapeutic advantage in sevoflurane-induced neurodegeneration.

The impact of serum uric acid on psoriasis: NHANES 2005-2014 and Mendelian randomization.

Background: Psoriasis is a chronic systemic inflammatory disease, and hyperuricemia is a common comorbidity in patients with psoriasis. However, the exact relationship between uric acid levels and psoriasis remains unclear. This study aimed to explore the association between uric acid levels and psoriasis. Methods: Observational study participant data (≥16 years, n = 23,489) from NHANES 2003-2014. We conducted analyses using a weighted multiple logistic regression model. Genetic data sets for uric acid levels and psoriasis were obtained from the IEU database. We selected genetically independent loci closely associated with serum uric acid levels as instrumental variables and performed Mendelian randomization analyses using five complementary methods: inverse variance weighting (IVW), MR-Egger, weighted median, simple mode, and weighted mode. Results: After adjusting for other covariates, the results revealed no significant association between serum uric acid levels and psoriasis (b = 0.999, 95% CI: 0.998, 1.001, p = 0.275). Subgroup analyses stratified by gender and ethnicity showed no significant association between sUA and psoriasis in any of the subgroups. Furthermore, the MR analysis involved the selection of 227 SNPs that were associated with both sUA and psoriasis. IVW results demonstrated no causal relationship between sUA and psoriasis (OR = 0.282, 95% CI: -0.094-0.657, p = 0.142). Conclusion: Our study suggests that uric acid levels are not significantly causally related to psoriasis. This finding provides valuable insights for the treatment and prevention of psoriasis, indicating that merely reducing uric acid levels may not be an effective strategy to reduce the risk of psoriasis onset.

Proteomic Insights into Osteoporosis: Unraveling Diagnostic Markers of and Therapeutic Targets for the Metabolic Bone Disease.

Osteoporosis (OP), a prevalent skeletal disorder characterized by compromised bone strength and increased susceptibility to fractures, poses a significant public health concern. This review aims to provide a comprehensive analysis of the current state of research in the field, focusing on the application of proteomic techniques to elucidate diagnostic markers and therapeutic targets for OP. The integration of cutting-edge proteomic technologies has enabled the identification and quantification of proteins associated with bone metabolism, leading to a deeper understanding of the molecular mechanisms underlying OP. In this review, we systematically examine recent advancements in proteomic studies related to OP, emphasizing the identification of potential biomarkers for OP diagnosis and the discovery of novel therapeutic targets. Additionally, we discuss the challenges and future directions in the field, highlighting the potential impact of proteomic research in transforming the landscape of OP diagnosis and treatment.

Efficacy and safety of simple analgesics for acute treatment of episodic tension-type headache in adults: a network meta-analysis.

OBJECTIVE: Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the efficacy and safety of simple analgesics for the treatment of episodic tension-type headache (ETTH) in adults. METHODS: We searched the Cochrane Library, PubMed, Web of Science, Embase, Chinese BioMedical Literature database and International Clinical Trials Registry Platform databases for eligible randomized clinical trials reporting the efficacy and/or safety of simple analgesics. A Bayesian NMA was performed to compare relative efficacy and safety. The surface under the cumulative ranking curve (SUCRA) was calculated to rank interventions. PROSPERO registration number: CRD42018090554. RESULTS: We highlighted six studies including 3507 patients. For the 2 h pain-free rate, the SUCRA ranking was ibuprofen > diclofenac-K > ketoprofen > acetaminophen > naproxen > placebo. All drugs except naproxen reported a higher 2 h pain-free rate than placebo, with a risk ratio (RR) of 2.86 (95% credible interval, CrI: 1.62-5.42) for ibuprofen and 2.61 (1.53-4.88) for diclofenac-K. For adverse events rate, the SUCRA ranking was: metamizol > diclofenac-K > ibuprofen > lumiracoxib > placebo > aspirin > acetaminophen > naproxen > ketoprofen. The adverse event rates of all analgesics were no higher than those of placebo, except for ketoprofen. Moreover, all drugs were superior to placebo in the global assessment of efficacy. In particular, the RR of lumiracoxib was 2.47 (1.57-4.57). Global heterogeneity I2 between the studies was low. CONCLUSIONS: Simple analgesics are considered more effective and safe as a placebo for ETTH in adults. Our results suggest that ibuprofen and diclofenac-K may be the two best treatment options for patients with ETTH from a comprehensive point of view (both high-quality evidence).

To our knowledge, this is the first network meta-analysis comparing the available data on adult patients with episodic tension-type headache (ETTH) treated with different simple analgesics recommended by the current guidelines.Ibuprofen (400 mg) and diclofenac-K (12.5 mg, 25 mg) are potentially the most effective and safe treatment options, supported by high-quality evidence.

Extended procedure has no oncological benefits over segmental resection in the treatment of non-metastatic splenic flexure colon cancer, a population-based cohort study and a single center's decade-long experience.

To compare the oncological survival outcome between extended resections (ER) and segmental resection (SR) for non-metastatic splenic flexure tumors. A total of 10,063 splenic flexure colon cancers patients who underwent ER (n = 5546) or SR (n = 4517) from 2010 to 2018 were included from the Surveillance, Epidemiology, and End Results (SEER)-registered database. Additionally, we included 135 patients from our center who underwent ER (n = 54) or SR (n = 81) between 2011 and 2021. Survival rates were compared between groups. To reduce the inherent bias of retrospective studies, propensity score matching (PSM) analysis was performed. In the SEER database, patients in the ER group exhibited higher pT stage, pN stage, larger tumor size, and elevated rates of CEA level, perineural invasion, and tumor deposits compared to those in the SR group (each P < 0.05). The 5-year cancer-specific survival (CSS) rate was slightly lower in the ER group than in the SR group (79.2% vs. 81.6%, P = 0.002), while the 5-year overall survival (OS) rates were comparable between the two groups (66.2% vs. 66.9%, P = 0.513). After performing PSM, both the 5-year CSS and 5-year OS rates were comparable between the ER and SR groups (5-year CSS: 84.9% vs. 83.0%, P = 0.577; 5-year OS: 70.6% vs. 66.0%, P = 0.415). These findings were consistent in the subgroup analysis that included only patients with stage III disease or tumor size ≥ 7 cm. Furthermore, although the number of harvested lymph nodes was higher in the ER group compared to the SR group (14.4 vs. 12.7, P < 0.001), the number of invaded lymph nodes remained similar between the two groups (0.5 vs. 0.5, P = 0.90). Similarly, our center's data revealed comparable 3-year OS and 3-year disease-free survival (DFS) rates between the two groups. ER have no significant oncological benefits over SR in the treatment of non-metastatic splenic flexure colon cancer, even for locally advanced cases.

Mixed-mode oscillations in a three-timescale coupled Morris-Lecar system.

Mixed-mode oscillations (MMOs) are complex oscillatory behaviors of multiple-timescale dynamical systems in which there is an alternation of large-amplitude and small-amplitude oscillations. It is well known that MMOs in two-timescale systems can arise either from a canard mechanism associated with folded node singularities or a delayed Andronov-Hopf bifurcation (DHB) of the fast subsystem. While MMOs in two-timescale systems have been extensively studied, less is known regarding MMOs emerging in three-timescale systems. In this work, we examine the mechanisms of MMOs in coupled Morris-Lecar neurons with three distinct timescales. We investigate two kinds of MMOs occurring in the presence of a singularity known as canard-delayed-Hopf (CDH) and in cases where CDH is absent. In both cases, we examine how features and mechanisms of MMOs vary with respect to variations in timescales. Our analysis reveals that MMOs supported by CDH demonstrate significantly stronger robustness than those in its absence. Moreover, we show that the mere presence of CDH does not guarantee the occurrence of MMOs. This work yields important insights into conditions under which the two separate mechanisms in two-timescale context, canard and DHB, can interact in a three-timescale setting and produce more robust MMOs, particularly against timescale variations.

Application of poly(L-lactic acid)-based films for equilibrium modified atmosphere packaging of "Kyoho" grapes and its favorable protection for anthocyanins.

Grapes were packaged by different Poly (L-lactic acid)-based packaging films (PLTL-PLEL) and stored at 5 °C for 35 days to investigate the effects of equilibrium modified atmosphere packaging on the quality of "Kyoho" grapes during storage. Changes in physiochemical quality, antioxidant content and senescence of grapes were studied. Furthermore, UPLC-Q-TOF-MS/MS was used to observe and identify key factors influencing the variation of grape anthocyanins under different atmosphere conditions. Alterations in gas components and enzyme activities significantly impacted anthocyanin levels, highlighting oxygen concentration as the primary influence on total anthocyanin levels. The PLTL-PLEL50 packaging resulted in an approximate 5.7% lower weight loss and increased soluble solids by approximately 14.4%, vitamin C, total phenols and flavonoids reaching 60.2 mg/100 g, 8.4 mg/100 g and 7.2 mg/100 g, respectively. This packaging also preserved higher anthocyanin levels, with malvidin-3-glucoside and peonidin-3-glucoside at 0.55 µg/mL and 1.62 µg/mL, respectively, on the 35th day of storage.

Cu2O-catalyzed cascade phosphinylation/cyclization of 2'-aminochalcones for the synthesis of hemi-indigo derivatives.

A Cu2O-catalyzed cascade phosphinylation/cyclization reaction of 2'-aminochalcones and diphenylphosphine oxides to produce hemi-indigo derivatives has been developed. This strategy facilitates the sequential formation of a C-P bonds and a C-N bond in a single reaction step. Notably, the approach features one-pot operation, an earth-abundant copper catalyst, readily available starting materials, a broad substrate scope and high compatibility with functional groups, providing 33 compounds in acceptable yields.

The influence of elongation-induced concentration fluctuations on segmental friction in polymer blends.

Recent experimental studies have revealed a lack of universality in the extensional behavior of linear polymers, which is not envisioned by classical molecular theories. These surprising findings, particularly the sharp contrast between polymer melts and solutions, have catalyzed the development of new theoretical ideas, including the concept of friction reduction in highly stretched polymer melts. By presenting evidence from rheology and small-angle neutron scattering, this work shows that deformation-induced demixing, which is due to the viscoelastic asymmetry in binary mixtures, contributes to the observed nonuniversality. In the case of polystyrene/oligostyrene blends, demixing increases the effective glass transition temperature of the long chain, leading to an apparent friction enhancement. On the other hand, the opposite case is found for the polystyrene/poly(α-methylstyrene) blend. These results highlight the important influence of deformation-induced concentration fluctuations on polymer segmental friction.

A dual-mode label-free electrochemical immunosensor for ultrasensitive detection of procalcitonin by on-site vulcanization of dual-MOF heterostructure.

Detection of procalcitonin (PCT) is crucial for the early identification of sepsis. PCT is primarily utilized in the multiple diagnosis of bacterial and viral illnesses along with to guide the application of antibiotics. Considering their advantages of high specificity and straightforward usage, electrochemical immunosensors offer significant application prospects in the detection of disease indicators. A dual-mode electrochemical immunosensor was constructed in this study to reliably identify PCT. In light of the synergistic effect of the dual-MOF derived heterostructure, the immunosensor demonstrating excellent square wave voltammetry (SWV) signals as well as significant catalytic activity for the H2O2 redox process. In addition to maintaining a low detection limit (SWV: 0.31 fg/mL and i-t: 0.098 fg/mL), the immunosensor offers an extensive linear response range (0.000001-100 ng/mL). The excellent performance is on account of the introduction of the local on-site sulfurized dual-MOF heterostructure with abundant metal chalcogenides/MOF interfaces, which boosts the specific surface area, offers an abundance of active sites, enhances conductivity, and raises catalytic activity. Furthermore, the immunosensor exhibits outstanding specificity, stability and reproducibility for the determination of PCT in serum, which is of great crucial for the clinical screening and diagnosis of sepsis.

Peripheral cutaneous synucleinopathy characteristics in genetic Parkinson's disease.

Background: Cutaneous phosphorylated alpha-synuclein (p-α-syn) deposition is an important biomarker of idiopathic Parkinson's disease (iPD). Recent studies have reported synucleinopathies in patients with common genetic forms of PD. Objective: This study aimed to detect p-α-syn deposition characteristic in rare genetic PD patients with CHCHD2 or RAB39B mutations. Moreover, this study also aimed to describe peripheral alpha-synuclein prion-like activity in genetic PD patients, and acquire whether the cutaneous synucleinopathy characteristics of genetic PD are consistent with central neuropathologies. Methods: We performed four skin biopsy samples from the distal leg (DL) and proximal neck (C7) of 161 participants, including four patients with CHCHD2 mutations, two patients with RAB39B mutations, 16 patients with PRKN mutations, 14 patients with LRRK2 mutations, five patients with GBA mutations, 100 iPD patients, and 20 healthy controls. We detected cutaneous synucleinopathies using immunofluorescence staining and a seeding amplification assay (SAA). A systematic literature review was also conducted, involving 64 skin biopsies and 205 autopsies of genetic PD patients with synucleinopathy. Results: P-α-syn was deposited in the peripheral cutaneous nerves of PD patients with CHCHD2, LRRK2, or GBA mutations but not in those with RAB39B or PRKN mutations. There were no significant differences in the location or rate of α-syn-positive deposits between genetic PD and iPD patients. Peripheral cutaneous synucleinopathy appears to well represent brain synucleinopathy of genetic PD, especially autosomal dominant PD (AD-PD). Cutaneous α-synuclein SAA analysis of iPD and LRRK2 and GBA mutation patients revealed prion-like activity. Conclusion: P-α-syn deposition in peripheral cutaneous nerves, detected using SAA and immunofluorescence staining, may serve as an accurate biomarker for genetic PD and iPD in the future.

Repeat biopsy versus initial biopsy in terms of complication risk factors and clinical outcomes for patients with non-small cell lung cancer: a comparative study of 113 CT-guided needle biopsy of lung lesions.

Objectives: The safety and feasibility of repeat biopsy after systemic treatment for non-small cell lung cancer have received extensive attention in recent years. The purpose of this research was to compare complication rates between initial biopsy and rebiopsy in non-small cell lung cancer patients with progressive disease and to assess complication risk factors and clinical results after rebiopsy. Methods: The study included 113 patients initially diagnosed with non-small cell lung cancer who underwent lung biopsy at initial biopsy and rebiopsy after progression while on epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and/or chemotherapy from January 2018 to December 2021. We compared the incidence of complications between the initial biopsy and rebiopsy and analyzed the predictors factors that influenced complications in patients who underwent rebiopsy. Results: The successful rate of rebiopsy was 88.5% (100/113). With the exception of two cases where lung adenocarcinoma changed into small cell lung cancer with gefitinib treatment, 98 individuals retained their initial pathological type. The secondary EGFR T790M mutation accounts for 55.6% of acquired resistance. The total number of patients with complications in initial biopsy was 25 (22.1%) and 37 (32.7%) in the rebiopsy. The incidence of pulmonary hemorrhage increased from 7.1% at the initial biopsy to 10.6% at rebiopsy, while the incidence of pneumothorax increased from 14.2% to 20.4%. Compared with the initial biopsy, the incidence of overall complications, parenchymal hemorrhage, and pneumothorax increased by 10.6%, 3.5%, and 6.2%, respectively. In all four evaluations (pneumorrhagia, pneumothorax, pleural reaction, and overall complication), there were no significant differences between the rebiopsy and initial biopsy (all p > 0.05). The multivariate logistic regression analysis suggested that male sex (odds ratio [OR] = 5.064, p = 0.001), tumor size ≤ 2 cm (OR = 3.367, p = 0.013), EGFR-TKIs with chemotherapy (OR = 3.633, p =0.023), and transfissural approach (OR = 7.583, p = 0.026) were independent risk factors for overall complication after rebiopsy. Conclusion: Compared with the initial biopsy, the complication rates displayed a slight, but not significant, elevation in rebiopsy. Male sex, tumor size ≤ 2 cm, transfissural approach, and EGFR-TKIs combined with chemotherapy were independent risk factors for rebiopsy complications.

Hovenia dulcis: a Chinese medicine that plays an essential role in alcohol-associated liver disease.

Globally, alcohol-associated liver disease (ALD) has become an increased burden for society. Disulfirams, Benzodiazepines (BZDs), and corticosteroids are commonly used to treat ALD. However, the occurrence of side effects such as hepatotoxicity and dependence, impedes the achievement of desirable and optimal therapeutic efficacy. Therefore, there is an urgent need for more effective and safer treatments. Hovenia dulcis is an herbal medicine promoting alcohol removal clearance, lipid-lowering, anti-inflammatory, and hepatoprotective properties. Hovenia dulcis has a variety of chemical components such as dihydromyricetin, quercetin and beta-sitosterol, which can affect ALD through multiple pathways, including ethanol metabolism, immune response, hepatic fibrosis, oxidative stress, autophagy, lipid metabolism, and intestinal barrier, suggesting its promising role in the treatment of ALD. Thus, this work aims to comprehensively review the chemical composition of Hovenia dulcis and the molecular mechanisms involved in the process of ALD treatment.

The beneficial effect of α-lipoic acid on spinal cord injury repair in rats is mediated through inhibition of oxidative stress: A transcriptomic analysis.

BACKGROUND: Oxidative stress is a crucial factor contributing to the occurrence and development of secondary damage in spinal cord injuries (SCI), ultimately impacting the recovery process. α-lipoic acid (ALA) exhibits potent antioxidant properties, effectively reducing secondary damage and providing neuroprotective benefits. However, the precise mechanism by which ALA plays its antioxidant role remains unknown. METHODS: We established a model of moderate spinal cord contusion in rats. Experimental rats were randomly divided into 3 distinct groups: the sham group, the model control group (SCI_Veh), and the ALA treatment group (SCI_ALA). The sham group rats were exposed only to the SC without contusion injury. Rats belonging to SCI_Veh group were not administered any treatment after SCI. Rats of SCI_ALA group were intraperitoneally injected with the corresponding volume of ALA according to body weight for three consecutive days after the surgery. Subsequently, three days after SCI, spinal cord samples were obtained from three groups of rats: the sham group, model control group, and administration group. Thereafter, total RNA was extracted from the samples and the expression of three sets of differential genes was analyzed by transcriptome sequencing technology. Real-time PCR was used to verify the sequencing results. The impact of ALA on oxidative stress in rats following SCI was assessed by measuring their total antioxidant capacity and hydrogen peroxide (H2O2) content. The effects of ALA on rat recovery following SCI was investigated through Beattie and Bresnahan (BBB) score and footprint analysis. RESULTS: The findings from the transcriptome sequencing analysis revealed that the model control group had 2975 genes with altered expression levels when compared to the ALA treatment group. Among these genes, 1583 were found to be upregulated while 1392 were down-regulated. Gene ontology (GO) displayed significant enrichment in terms of functionality, specifically in oxidative phosphorylation, oxidoreductase activity, and signaling receptor activity. The Kyoto encyclopedia of genes and genomes (KEGG) pathway was enriched in oxidative phosphorylation, glutathione metabolism and cell cycle. ALA was found to have multiple benefits for rats after SCI, including increasing their antioxidant capacity and reducing H2O2 levels. Additionally, it was effective in improving motor function (such as 7 days after SCI, the BBB score for SCI_ALA was 8.400 ± 0.937 compared to 7.050 ± 1.141 for SCI_Veh) and promoting histological recovery after SCI (The results of HE demonstrated that the percentage of damage area in was 44.002 ± 6.680 in the SCI_ALA and 57.215 ± 3.964 in the SCI_Veh at the center of injury.). The sequence data from this study has been deposited into Sequence Read Archive (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE242507). CONCLUSION: Overall, the findings of this study confirmed the beneficial effects of ALA on recovery in SCI rats through transcriptome sequencing, behavioral, as well histology analyses.

Linc-NSC affects cell differentiation, apoptosis and proliferation in mouse neural stem cells and embryonic stem cells in vitro and in vivo.

BACKGROUND: Stem cell therapy is a promising therapeutic strategy. In a previous study, we evaluated tumorigenicity by the stereotactic transplantation of neural stem cells (NSCs) and embryonic stem cells (ESCs) from experimental mice. Twenty-eight days later, there was no evidence of tumor formation or long-term engraftment in the NSCs transplantation group. In contrast, the transplantation of ESCs caused tumor formation; this was due to their high proliferative capacity. Based on transcriptome sequencing, we found that a long intergenic non-coding RNA (named linc-NSC) with unknown structure and function was expressed at 1100-fold higher levels in NSCs than in ESCs. This finding suggested that linc-NSC is negatively correlated with stem cell pluripotency and tumor development, but positively correlated with neurogenesis. In the present study, we investigated the specific role of linc-NSC in NSCs/ESCs in tumor formation and neurogenesis. METHODS: Whole transcriptome profiling by RNA sequencing and bioinformatics was used to predict lncRNAs that are widely associated with enhanced tumorigenicity. The expression of linc-NSC was assessed by quantitative real-time PCR. We also performed a number of in vitro methods, including cell proliferation assays, differentiation assays, immunofluorescence assays, flow cytometry, along with in vivo survival and immunofluorescence assays to investigate the impacts of linc-NSC on tumor formation and neurogenesis in NSCs and ESCs. RESULTS: Following the knockdown of linc-NSC in NSCs, NSCs cultured in vitro and those transplanted into the cortex of mice showed stronger survival ability (P < 0.0001), enhanced proliferation(P < 0.001), and reduced apoptosis (P < 0.05); the opposite results were observed when linc-NSC was overexpressed in ESCs. Furthermore, the overexpression of linc-NSC in ECSs induced enhanced apoptosis (P < 0.001) and differentiation (P < 0.01), inhibited tumorigenesis (P < 0.05) in vivo, and led to a reduction in tumor weight (P < 0.0001). CONCLUSIONS: Our analyses demonstrated that linc-NSC, a promising gene-edited target, may promote the differentiation of mouse NSCs and inhibit tumorigenesis in mouse ESCs. The knockdown of linc-NSC inhibited the apoptosis in NSCs both in vitro and in vivo, and prevented tumor formation, revealing a new dimension into the effect of lncRNA on low survival NSCs and providing a prospective gene manipulation target prior to transplantation. In parallel, the overexpression of linc-NSC induced apoptosis in ESCs both in vitro and in vivo and attenuated the tumorigenicity of ESCs in vivo, but did not completely prevent tumor formation.