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The image of dazed, plague-infected rats coming out of their nests and performing a pirouette in front of the surprised eyes of humans before dying is one well-known to us through Albert Camus's The Plague (1947). This article examines the historical roots of this image and its emergence in French missionary narratives about plague outbreaks in the Chinese province of Yunnan in the 1870s on the eve of the Third Plague Pandemic. Showing that accounts of the "staggering rat" were not meant as naturalist observations of a zoonotic disease, as is generally assumed by historians, but as a cosmological, end-of-the-world narrative with a colonial agenda, the article argues for an approach to historical accounts of epidemics that does not succumb to the current trend of "virus hunting" in the archive, but rather takes colonial outbreak narratives ethnographically seriously. [ABSTRACT FROM AUTHOR]

Objective: To investigate the independent effects of irisin on insulin resistance (IR) in ovary of polycystic ovary syndrome (PCOS) and explore possible pathways. Methods: We established PCOS medel using Poretsky L's method, then PCOS rats were randomly divided into model group (M) and irisin group (I), and normal rats (N) were used as the control. Then rats in the group I were injected with recombinant irisin. Then the levels of circulating fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of IR (HOMA‐IR) and PI3K/AKT and MAPK/ERK pathways in each group were observed, as well as the effects of irisin on the levels of circulating HOMA‐IR and PI3K/AKT and MAPK/ERK pathways in ovary of PCOS rats were evaluated. Results: Compared with normal group, levels of FBG, FINS, and HOMA‐IR of model group were significantly increased (p < 0.001, p < 0.001, and p < 0.001, respectively), levels of average optical density by IHC of p‐PI3K, PI3K, p‐AKT, and AKT (p = 0.015, p = 0.010, p = 0.005, and p = 0.009, respectively) and levels of mRNA concentration of PI3K and AKT (p = 0.001, and p = 0.005, respectively) were decreased, while the levels of average optical density of p‐ERK, ERK (p = 0.011, and p = 0.013, respectively) and level of mRNA concentration of ERK (p < 0.001) were increased in ovary. After irisin intervention, compared with model group, levels of FBG, FINS, and HOMA‐IR of rats in irisin group were significantly decreased (p = 0.001, p < 0.001, and p < 0.001, respectively), levels of average optical density by IHC of p‐PI3K, PI3K, p‐AKT, and AKT (p = 0.030, p = 0.024, p = 0.012, and p = 0.025, respectively) and levels of mRNA concentration of PI3K and AKT (p = 0.002, and p = 0.003, respectively) were significantly increased, while the levels of average optical density of p‐ERK, ERK (p = 0.004, and p = 0.026, respectively) and level of mRNA concentration of ERK (p = 0.001) were significantly decreased. Conclusion: Our study demonstrated that irisin could not only improve circulating insulin resistance, but may also improve ovarian IR through an increase in the activity of PI3K/AKT signaling and a decrease of MAPK/ERK signaling. [ABSTRACT FROM AUTHOR]

Objectives: Osteoporosis is widely regarded as a typical aged-related disease caused by impaired bone remodeling. This research was designed to explore the protective effects of electroacupuncture (EA) on senile osteoporosis in a rat model and investigate the underlying mechanisms. Methods: Three-month-old rats were randomly selected as the youth group, and 24-month-old rats were randomly assigned to the elderly and EA groups. Rats in the EA group received 30 min of EA at bilateral SP10, ST36, K13 and GB34 daily, 5 days a week for 8 weeks. Bone mineral density (BMD), microstructure of the bone tissue, bone turnover biomarkers and expression level of autophagy-related proteins were detected. Results: Compared with the elderly group, EA treatment significantly increased BMD of the femur and ameliorated the microstructure. EA treatment increased trabecular bone volume ratio (= bone volume / total volume [BV/TV]) and trabecular number (Tb.N) and decreased trabecular separation (Tb.Sp) in senile osteoporosis rats. Compared with the elderly group, the serum N-terminal telopeptide of type I collagen (NTX1) level in the EA group was lower, and the serum procollagen type I N-terminal propeptide (PINP) concentration was higher. In addition, the expression of Beclin 1, microtubule-associated protein I light chain 3 (LC3B) and P62 was inhibited in the senile osteoporosis rats after EA treatment. Conclusions: EA can effectively alleviate aging-related bone loss and improve the microstructure of bone tissue in senile osteoporosis rats, and the regulation of autophagy might be one of the important mechanisms. [ABSTRACT FROM AUTHOR]

Background: Gegen Qinlian Decoction (GQD) is a classical traditional Chinese medicine (TCM) formula primarily utilized for treating gut disorders. GQD showed therapeutic effects on several diseases in clinical and animal studies by targeting gut microbes. Our recent studies also found that GQD efficiently alleviated anxiety in methamphetamine-withdrawn mice via regulating gut microbiome and metabolism. Given that various studies have indicated the link between the gut microbiome and the development of depression, here we endeavor to explore whether GQD can manage depression disorders by targeting the gut microbiome. Methods and materials: The depression-like model was induced in rats through chronic unpredictable mild stress (CUMS) and the depression levels were determined using the sucrose preference test (SPT). To address the depression-like behavior in rats, oral administration of GQD was employed. The colon microbiome and metabolite patterns were determined by 16s rRNA sequencing and untargeted metabolomics, respectively. Results: We found 6 weeks of CUMS can induce depression-like behavior in rats and 4 weeks of GQD treatment can significantly alleviate the depression-like behavior. GQD treatment can also ameliorate the histological lesions in the colon of CUMS rats. Then, CUMS increased the abundance of gut microbes, while GQD treatment can restore it to a lower level. We further discovered that the abundances of 19 bacteria at the genus level were changed with CUMS treatment, among which the abundances of Ruminococcus, Lachnoclostridium, Pygmaiobacter, Bacteroides, Pseudomonas, and Pseudomonas Family_XIII_AD3011_group were stored by GQD treatment. Besides, we identified the levels of 36 colon metabolites were changed with CUMS treatment, among which the levels of Fasciculic acid B, Spermine, Fludrocortisone acetate, alpha-Ketoglutaric acid, 2-Oxoglutaric acid, N'-(benzoyloxy)-2-(2,2-dichlorocyclopropyl) ethanimidamide, N6-Succinyl Adenosine Oleanolic acid, KQH, Ergosta-5,7,9(11),22-Tetraen-3-beta-Ol, Gentisic acid, 4-Hydroxyretinoic Acid, FAHFA (3:0/16:0), Leucine-enkephalin and N-lactoyl-phenylalanine can be restored by GQD treatment. Conclusion: Our findings provide evidence supporting the therapeutic efficacy of GQD in alleviating depression-like behavior in CUMS rats, potentially being targeted on colon bacteria (especially the abundance of Ruminococcus and Bacteroides) and metabolites (especially the level of Oleanolic acid). [ABSTRACT FROM AUTHOR]

Subarachnoid hemorrhage (SAH) is a severe subtype of hemorrhagic stroke. The molecular mechanisms of its secondary brain damage remain obscure. To investigate the alterations in gene and metabolite levels following SAH, we construct the transcriptome and metabolome profiles of the rat cerebral cortex post-SAH using whole transcriptome sequencing and untargeted metabolomics assays. Transcriptomic analysis indicated that there were 982 differentially expressed genes (DEGs) and 540 differentially expressed metabolites (DEMs) between the sham group and SAH 1d, and 292 DEGs and 254 DEMs between SAH 1d and SAH 7d. Most notably, DEGs were predominantly involved in the activation of immune and inflammatory pathways, particularly the Complement and coagulation cascades, TNF signaling pathway, and NOD-like receptor signaling pathway. Metabolic analysis revealed that the metabolic pathways of Arginine and proline, Arachidonic acid, Folate biosynthesis, Pyrimidine, and Cysteine and methionine were remarkably affected after SAH. Metabolites of the above pathways are closely associated not only with immune inflammation but also with oxidative stress, endothelial cell damage, and blood-brain barrier disruption. This study provides new insights into the underlying pathologic mechanisms of secondary brain injury after SAH and further characterization of these aberrant signals could enable their application as potential therapeutic targets for SAH. [ABSTRACT FROM AUTHOR]

Objective: Studies have shown that chemokines can stimulate the migration and activation of microglia to cause chronic post-surgical pain (CPSP). However, the involvement of C-X-C motif chemokine receptor 2 (CXCR2) as a new chemotactic factor in regulating CPSP and its underlying mechanism remains unclear. This study is to investigate the role of CXCR2 in the development of CPSP and reveal the underlying mechanism. Material and Methods: A rat model of skin/muscle incision and retraction was established, and treated with or without SB225002 (a selective inhibitor of CXCR2). In addition, the primary microglia cells induced by lipopolysaccharide were applied as an in vitro model for CPSP and treated individually with si-negative control (NC), si-CXCR2, si-CXCR2+Interleukin (IL)-6 (an agonist of the janus kinase (JAK)/signal transducers and activators of transcription (STAT)3 signaling pathway), si-CXCR2+IL-6+si-NC, or si-CXCR2+IL-6+si-exchange protein 1 directly activated by cAMP (EPAC1). Results: Results from the database analysis showed that CXCR2 and JAK/STAT3 signaling pathway-related genes, including JAK1, STAT3, and EPAC1, were mainly involved in the development of CPSP. Inhibition of CXCR2 expression not only inhibited the reduction of foot pain threshold in CPSP models but also led to a decreased expression of CXCR2 and the phosphorylation levels of JAK and STAT3 in both animal and cell models. Furthermore, inhibition of EPAC1 expression can hinder the regulatory function of CXCR2. Conclusion: This study indicated that the high expression of CXCR2 activates the JAK1/STAT3 signaling pathway, enhances EPAC1 activation in microglial cells, and exacerbates CPSP. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS) is a precursor to the development of many diseases (atherosclerosis, diabetes, etc.). It is marked by disruptions in glucose and lipid metabolism, along with hypertension. Numerous types of risk factors contribute to the development of the MetS, inflammation and insulin resistance are present throughout the metabolic abnormalities. Chrysanthemum indicum L. is a traditional Chinese plant used for both tea and medicine, known for its high content of total flavonoids, which are important secondary metabolites. Our research led to the extraction of a Buddleoside-Rich Chrysanthemum indicum L. extract (BUDE) which has demonstrated anti-inflammatory properties. Nonetheless, the specific role and mechanism of BUDE in preventing MetS remain unclear. Methods: The study initially evaluated the role of BUDE in preventing MetS. Subsequently, it investigated the anti-inflammatory properties of BUDE in the liver and pancreas in response to unhealthy diets. It then examined the level of insulin resistance and pancreatic β-cell function induced by inflammation. Additionally, an lipopolysaccharide (LPS)-induced macrophage inflammation model was used to further investigate the ameliorative effects of BUDE in inflammation. Results: BUDE has hypotensive, hypoglycemic and hypolipidemic effects. It can also resolve the imbalance between macrophage subpopulations, impede the triggering of the NF-κB signaling pathway, reduce the secretion of inflammatory mediators, ameliorate insulin resistance, and safeguard organs such as the liver and pancreas from inflammatory damage. These effects collectively contribute to preventing the development of MetS. Discussion: BUDE has the ability to modulate macrophage-mediated inflammation, leading to improved insulin resistance. Additionally, it delivers antihypertensive, hypoglycemic, and hypolipidemic effects, offering a potential for preventing MetS. [ABSTRACT FROM AUTHOR]

Background: Salidroside is the major bioactive and pharmacological active substance in Rhodiola rosea L. It has been reported to have neuroprotective effects on cerebral ischemia/reperfusion (I/R). However, whether salidroside can enhance neural regeneration after cerebral I/R is still unknown. This study investigated the effects of salidroside on the endogenous neural regeneration after cerebral I/R and the related mechanism. Methods: Focal cerebral I/R was induced in rats by transient middle cerebral artery occlusion/reperfusion (MCAO/R). The rats were intraperitoneally treated salidroside once daily for 7 consecutive days. Neurobehavioral assessments were performed at 3 days and 7 days after the injury. TTC staining was performed to assess cerebral infarct volume. To evaluate the survival of neurons, immunohistochemical staining of Neuronal Nuclei (NeuN) in the ischemic hemisphere were conducted. Also, immunofluorescence double or triple staining of the biomarkers of proliferating neural progenitor cells in Subventricular Zone (SVZ) and striatum of the ischemia hemisphere were performed to investigate the neurogenesis. Furthermore, reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of neurotrophic factors (NTFs) brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Expression of Notch1 and its target molecular Hes1 were also analyzed by western-blotting and RT-PCR. Results: Salidroside treatment ameliorated I/R induced neurobehavioral impairment, and reduced infarct volume. Salidroside also restored NeuN positive cells loss after I/R injury. Cerebral I/R injury significantly increased the expression of 5-Bromo-2'-Deoxyuridine (BrdU) and doublecotin (DCX), elevated the number of BrdU/Nestin/DCX triple-labeled cells in SVZ, and BrdU/Nestin/glial fibrillary acidic protein (GFAP) triple-labeled cells in striatum. Salidroside treatment further promoted the proliferation of BrdU/DCX labeled neuroblasts and BrdU/Nestin/GFAP labeled reactive astrocytes. Furthermore, salidroside elevated the mRNA expression and protein concentration of BDNF and NGF in ischemia periphery area, as well. Mechanistically, salidroside elevated Notch1/Hes1 mRNA expression in SVZ. The protein levels of them were also increased after salidroside administration. Conclusions: Salidroside enhances the endogenous neural regeneration after cerebral I/R. The mechanism of the effect may involve the regulation of BDNF/NGF and Notch signaling pathway. [ABSTRACT FROM AUTHOR]

Simple Summary: Leptotrombidium imphalum (a chigger species) can serve as a transmitting vector of scrub typhus. Based on the field investigation in southwest China from 2001 to 2022, this article presents the first report on the distribution and infestation of L. imphalum on small mammals in the region. A total of 2161 L. imphalum were identified from 218 small mammal hosts that crossed three orders, and the majority of the mites were found on the order Rodentia (rodents). Different host species had different susceptibility to the infestation of L. imphalum, and the shrew gymnure (Neotetracus sinensis) was much more susceptible to the infestation than other host species. Leptotrombidium imphalum exhibited an aggregated distribution among different individuals of its hosts. The positive correlation between the infestation indices for L. imphalum on small mammals and the occurrence of scrub typhus, together with the low host specificity of the mite, indicates the potential risk of the mite. Leptotrombidium imphalum is a species of chigger mites, and it can serve as a transmitting vector of scrub typhus. Southwest China is an important focus of scrub typhus. Based on the field investigation in southwest China from 2001 to 2022, this article presents the first report on the distribution and infestation of L. imphalum on rodents and other sympatric small mammals in the region. A total of 2161 L. imphalum were identified from 218 small mammal hosts in 21 of 114 survey sites. The 17 host species of L. imphalum crossed 13 genera and 5 families in 3 orders (Rodentia, Eulipotyphla, and Scandentia), indicating the low host specificity of the mite. The Asian house rat (Rattus tanezumi) was the dominant host species in the 21 sites where L. imphalum were collected, and 49.38% of mites were found on R. tanezumi. Different small mammals had different susceptibility to the infestation of L. imphalum. The prevalence (PM = 27.66%), infestation mean abundance (MA = 6 mites/per examined host), and mean intensity (MI = 21.69 mites/per infested host) for L. imphalum on the shrew gymnure (Neotetracus sinensis) were much higher than those on other host species (p < 0.05), indicating N. sinensis had a high susceptibility to the infestation of L. imphalum. The infestation indices for L. imphalum on small mammal hosts varied along different altitude and latitude gradients (p < 0.05), indicating the environmental heterogeneity of the mite infestation. Leptotrombidium imphalum exhibited an aggregated distribution among different individuals of its hosts. Besides the low host specificity of L. imphalum, the prevalence of the mite was positively correlated with the occurrence of scrub typhus, indicating the potential risk of the mite. [ABSTRACT FROM AUTHOR]

Lithocarpus litseifolius although known as "Sweet Tea" (ST), has been traditionally accepted as a daily beverage and used as a folk medicine in southern China with little understanding of its potential toxicity. This study evaluated the safety of a water extract of ST by a subchronic toxicity study in Sprague-Dawley rats. A total of 80 rats were randomized divided into 4 groups with 10 males and 10 females in each group, treated with 2000, 1,000, 500 and 0 mg/kg body weight of ST extract by gavage for 90 days, respectively. The results of the study showed that ST extract did not induce treatment-related changes in the body and organ weight, food intake, blood hematology and serum biochemistry, urine indices, and histopathology in rats. The NOAEL of ST extract was observed to be 2000 mg/kg/day for rats of both sexes. These results indicated that ST extract was of low toxicity in the experimental conditions of the current study and had the potential for application in food-related products. [ABSTRACT FROM AUTHOR]

Introduction. Transient global ischaemia in rodents causes selective loss of hippocampal CA1neurons, but the potential involvement of endocytic pathways has not been fully explored. The aim of this study was to investigate the changes in early endosomes in the CA1 subfield after ischaemia and reperfusion. Material and methods. A four-vessel occlusion (4-VO) model was established in Wistar rats to induce 13 minutes of global cerebral ischaemia. Neuronal death was detected by Fluoro-Jade B (FJ-B) staining at various intervals after reperfusion, and intracellular membrane changes in ischaemic neurons were revealed using DiOC6(3), a lipophilic fluorescent probe. Ras-related protein Rab5 (Rab5) immunostaining was performed to detect changes in early endosomes in ischaemic neurons. Western blot analysis was used to confirm the morphological observations on Rab5 in the CA1 hippocampal subfield. Results. FJ-B staining confirmed progressive neuronal death in the CA1 subfield in ischaemic rats after reperfusion. DiOC6(3) staining revealed abnormally increased membranous components in ischaemic CA1 neurons. Specifically, early endosomes, as labelled by Rab5 immunostaining, significantly increased in number and size in CA1 neurons at 1.5 and 2 days post-reperfusion, followed by rupture at day 3 and a decrease in staining intensity at day 7 post-reperfusion. Western blot analysis confirmed a significant upregulation of Rab5 protein levels at day 2, which returned to near control levels by day 7. Conclusions. Our study revealed significant changes in the dynamics of early endosomes in CA1 neurons after ischaemia-reperfusion injury. The initial increase in the area fraction of early endosomes in CA1 neurons may reflect an upregulation of endocytic activity, whereas the fragmentation and reduction of early endosomes at the later stage may indicate a failure of adaptive mechanisms of ischaemic neurons against ischaemia-induced death. Understanding the temporal dynamics of early endosomes provides critical insights into the cellular mechanisms that govern fate of CA1 hippocampal neuronsl after ischaemia/reperfusion. [ABSTRACT FROM AUTHOR]

Amdizalisib, also named HMPL-689, a novel selective and potent PI3Kd inhibitor, is currently under Phase II clinical development in China for treating hematological malignancies. The preclinical pharmacokinetics (PK) of amdizalisib were extensively characterized in vitro and in vivo to support the further development of amdizalisib. We characterized the plasma protein binding, blood-to-plasma partition ratio, cell permeability, hepatic microsomal metabolic stability, and drug-drug interaction potential of amdizalisib using in vitro experiments. In vivo PK assessment was undertaken in mice, rats, dogs, and monkeys following a single intravenous or oral administration of amdizalisib. The tissue distribution and excretion of amdizalisib were evaluated in rats. The PK parameters (CL and Vss) of amdizalisib in preclinical species (mice, rats, dogs, and monkeys) were utilized for the human PK projection using the allometric scaling (AS) approach. Amdizalisib was well absorbed and showed low-to-moderate clearance in mice, rats, dogs, and monkeys. It had high cell permeability without P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) substrate liability. Plasma protein binding of amdizalisib was high (approximately 90%). It was extensively distributed but with a low brain-to-plasma exposure ratio in rats. Amdizalisib was extensively metabolized in vivo, and the recovery rate of the prototype drug was low in the excreta. Amdizalisib and/or its metabolites were primarily excreted via the bile and urine in rats. Amdizalisib showed inhibition potential on P-gp but not on BCRP and was observed to inhibit CYP2C8 and CYP2C9 with IC50 values of 30.4 and 10.7 µM, respectively. It exhibited induction potential on CYP1A2, CYP2B6, CYP3A4, and CYP2C9. The preclinical data from these ADME studies demonstrate a favorable pharmacokinetic profile for amdizalisib, which is expected to support the future clinical development of amdizalisib as a promising anti-cancer agent. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects the body. Periploca forrestii was a miao ethnic drug in China that was used to treat arthritis for hundreds of years. But, the therapeutic mechanism is so far unknown. Therefore, the chemical component and effect of Periploca forrestii on arthritis in rats were studied using HPLC-QTOF MS, micro-CT, and other experiments in this paper. Method: Male Sprague-Dawley rats were used to assess the in vivo activity. HPLC QTOF-MS was used to analyze the chemical profile of the P. forrestii (PF). Bovine type II collagen and Complete Freund's Adjuvant were used to stimulate and construct the collagen-induced arthritis (CIA) model. Three dosages of PF (100 mg/kg, 200 mg/kg, 400 mg/kg) were used to evaluate in vivo activity. Methotrexate was used as the positive drug. H/E staining and micro-CT methods were used to monitor the pathological changes of CIA rats. ELISA method was used to assess the serum level of immune- and inflammationrelated cytokines. Immunohistochemical experiments were used to test the gene expression in JAK and Nf-B pathways. Results: 42 compounds were identified from PF. PF administration lowered the increased spleen index compared with that of control and MTX groups, and partially restored body weight, reduced paw swelling, and arthritis score compared with the model group. Macroscopic assessment indicated inflamed paw with significant swelling in the model group, while the extent of inflammation and swelling was attenuated by both MTX and PF. H/E staining experiments demonstrated that pathological changes of synovial cells and infiltration of inflammatory cells were observed in the model group. In contrast, the MTX and PF treatment partially reversed these pathological changes. Micro-CT examination showed severe injuries and scars caused by inflammation for the model group, and in the high-dosage group (400 mg/kg) the inflammationcaused injuries and scars were dramatically ameliorated. Mechanism study showed that PF restored Nf-B phosphorylation and JAK2 expression compared with the model group. Conclusion: P. forrestii possesses a potent effect on CIA rats. Nf-B and JAK2 pathways are involved in its protective effect on CIA. [ABSTRACT FROM AUTHOR]

Objectives Our previous study showed that resveratrol (Res) attenuates apoptosis and mitochondrial dysfunction in alveolar epithelial cell injury induced by hyperoxia by activating the SIRT1/PGC-1α signaling pathway. In the present study, we investigated whether Res protects against hyperoxia-induced lung injury in neonatal rats by activating SIRT1/PGC-1α signaling pathway. Methods Naturally delivered neonatal rats were randomly divided into six groups: normoxia + normal saline, normoxia + dimethyl sulfoxide (DMSO), normoxia + Res, hyperoxia + normal saline, hyperoxia + DMSO, and hyperoxia + Res. Lung tissue samples were collected on postnatal days 1, 7, and 14. Hematoxylin and eosin staining was used to evaluate lung development. Dual-immunofluorescence staining, real-time polymerase chain reaction, and western blotting were used to evaluate the levels of silencing information regulator 2-related enzyme 1 (SIRT1), peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), nuclear respiratory factor 1 (Nrf1), Nrf2, transcription factor A (TFAM) and citrate synthase, the number of mitochondrial DNA (mtDNA) and mitochondria, the integrity of mtDNA, and the expression of TFAM in mitochondria. Results We found that hyperoxia insulted lung development, whereas Res attenuated the hyperoxia lung injury. Res significantly upregulated the levels of SIRT1, PGC-1α, Nrf1, Nrf2, TFAM, and citrate synthase; promoted TFAM expression in the mitochondria; and increased the copy number of ND1 and the ratio of ND4/ND1. Conclusion Our data suggest that Res attenuates hyperoxia-induced lung injury in neonatal rats, and this was achieved, in part, by activating the SIRT1/PGC-1α signaling pathway to promote mitochondrial biogenesis. Key Points Hyperoxia insulted lung development in neonatal rats. Resveratrol promoted mitochondrial biogenesis to attenuate hyperoxia lung injury in neonatal rats. Resveratrol, at least in part, promoted mitochondrial biogenesis by activating the SIRT1/PGC-1α signaling pathway. [ABSTRACT FROM AUTHOR]

Global climate change has led to shifts in the distribution ranges of many terrestrial species, promoting their migration from lower altitudes or latitudes to higher ones. Meanwhile, successful invaders have developed genetic adaptations enabling the colonization of new environments. Over the past 40 years, Rattus tanezumi (RT) has expanded into northern China (Northwest and North China) from its southern origins. We studied the cold adaptation of RT and its potential for northward expansion by comparing it with sympatric Rattus norvegicus (RN), which is well adapted to cold regions. Through population genomic analysis, we revealed that the invading RT rats have split into three distinct populations: the North, Northwest, and Tibetan populations. The first two populations exhibited high genetic diversity, while the latter population showed remarkably low genetic diversity. These rats have developed various genetic adaptations to cold, arid, hypoxic, and high-UV conditions. Cold acclimation tests revealed divergent thermoregulation between RT and RN. Specifically, RT exhibited higher brown adipose tissue activity and metabolic rates than did RN. Transcriptome analysis highlighted changes in genes regulating triglyceride catabolic processes in RT, including Apoa1 and Apoa4 , which were upregulated, under selection and associated with local adaptation. In contrast, RN showed changes in carbohydrate metabolism genes. Despite the cold adaptation of RT, we observed genotypic and phenotypic constraints that may limit its ability to cope with severe low temperatures farther north. Consequently, it is less likely that RT rats will invade and overlap with RN rats in farther northern regions. [ABSTRACT FROM AUTHOR]

Background: Cervical spondylosis (CS) is a prevalent disorder that can have a major negative impact on quality of life. Traditional conservative treatment has limited efficacy, and electroacupuncture (EA) is a novel treatment option. We investigated the application and molecular mechanism of EA treatment in a rat model of cervical intervertebral disk degeneration (CIDD). Methods: The CIDD rat model was established, following which rats in the electroacupuncture (EA) group received EA. For overexpression of IL-22 or inhibition of JAK2-STAT3 signaling, the rats were injected intraperitoneally with recombinant IL-22 protein (p-IL-22) or the JAK2-STAT3 (Janus kinase 2—signal transducer and activator of transcription protein 3) inhibitor AG490 after model establishment. Rat nucleus pulposus (NP) cells were isolated and cultured. Cell counting kit-8 and flow cytometry were used to analyze the viability and apoptosis of the NP cells. Expression of IL-22, JAK2 and STAT3 was determined using RT-qPCR. Expression of IL-22/JAK2-STAT3 pathway and apoptosis related proteins was detected by Western blotting (WB). Results: EA protected the NP tissues of CIDD rats by regulating the IL-22/JAK2-STAT3 pathway. Overexpression of IL-22 significantly promoted the expression of tumor necrosis factor (TNF)-α, IL-6, IL-1β, matrix metalloproteinase (MMP)3 and MMP13 compared with the EA group. WB demonstrated that the expression of IL-22, p-JAK2, p-STAT3, caspase-3 and Bax in NP cells of the EA group was significantly reduced and Bcl-2 elevated compared with the model group. EA regulated cytokines and MMP through activation of IL-22/JAK2-STAT3 signaling in CIDD rat NP cells. Conclusion: We demonstrated that EA affected apoptosis by regulating the IL-22/JAK2-STAT3 pathway in NP cells and reducing inflammatory factors in the CIDD rat model. The results extend our knowledge of the mechanisms of action underlying the effects of EA as a potential treatment approach for CS in clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: In order to evaluate the effect of methacrylated hyaluronic acid (HAMA) hydrogels containing the recombinant human amelogenin (rhAm) in vitro and in vivo. Background: The ultimate goal in treating periodontal disease is to control inflammation and achieve regeneration of periodontal tissues. In recent years, methacrylated hyaluronic acid (HAMA) containing recombinant human amyloid protein (rhAm) has been widely used as a new type of biomaterial in tissue engineering and regenerative medicine. However, there is a lack of comprehensive research on the periodontal regeneration effects of this hydrogel. This experiment aims to explore the application of photoresponsive recombinant human amelogenin‐loaded hyaluronic acid hydrogel for periodontal tissue regeneration and provide valuable insights into its potential use in this field. Materials and Methods: The effects of rhAm‐HAMA hydrogel on the proliferation of human periodontal ligament cells (hPDLCs) were assessed using the CCK‐8 kit. The osteogenic differentiation of hPDLCs was evaluated through ALP staining and real‐time PCR. Calvarial parietal defects were created in 4‐week‐old Sprague Dawley rats and implanted with deproteinized bovine bone matrix in different treatment groups. The animals were euthanized after 4 and 8 weeks of healing. The bone volume of the defect was observed by micro‐CT and histological analysis. Results: Stimulating hPDLCs with rhAm‐HAMA hydrogel did not significantly affect their proliferation (p >.05). ALP staining and real‐time PCR results demonstrated that the rhAm‐HAMA group exhibited a significant upregulation of osteoclastic gene expression (p <.05). Micro‐CT results revealed a significant increase in mineralized tissue volume fraction (MTV/TV%), trabecular bone number (Tb.N), and mineralized tissue density (MTD) of the bone defect area in the rhAm‐HAMA group compared to the other groups (p <.05). The results of hematoxylin and eosin staining and Masson staining at 8 weeks post‐surgery further supported the results of the micro‐CT. Conclusions: The results of this study indicate that rhAm‐HAMA hydrogel could effectively promote the osteogenic differentiation of hPDLCs and stabilize bone substitutes in the defects that enhance the bone regeneration in vivo. [ABSTRACT FROM AUTHOR]

Objective: To develop an interference-free and rapid method to elucidate Guanxin II (GX II)'s representative vasodilator absorbed bioactive compounds (ABCs) among enormous phytochemicals. Methods: The contents of ferulic acid, tanshinol, and hydroxysafflor yellow A (FTA) in GX II/rat serum after the oral administration of GX II (30 g/kg) were detected using ultra-performance liquid chromatography-mass spectrometry. Totally 18 rats were randomly assigned to the control group (0.9% normal saline), GX II (30 g/kg) and FTA (5, 28 and 77 mg/kg) by random number table method. Diastolic coronary flow velocity-time integral (VTI), i.e., coronary flow or coronary flow-mediated dilation (CFMD), and endothelium-intact vascular tension of isolated aortic rings were measured. After 12 h of exposure to blank medium or 0.5 mmol/L H2O2, endothelial cells (ECs) were treated with post-dose GX II of supernatant from deproteinized serum (PGSDS, 300 µL PGSDS per 1 mL of culture medium) or FTA (237, 1539, and 1510 mg/mL) for 10 min as control, H2O2, PGSDS and FTA groups. Nitric oxide (NO), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), superoxide dismutase (SOD), malondialdehyde (MDA) and phosphorylated phosphoinositide 3 kinase (p-PI3K), phosphorylated protein kinase B (p-AKT), phosphorylated endothelial nitric oxide synthase (p-eNOS) were analyzed. PGSDS was developed as a GX II proxy of ex vivo herbal crude extracts. Results: PGSDS effectively eliminates false responses caused by crude GX II preparations. When doses equaled the contents in GX II/its post-dose serum, FTA accounted for 98.17% of GX II -added CFMD and 92.99% of PGSDS-reduced vascular tension. In ECs, FTA/PGSDS was found to have significant antioxidant (lower MDA and higher SOD, P<0.01) and endothelial function-protective (lower VEGF, ET-1, P<0.01) effects. The increases in aortic relaxation, endothelial NO levels and phosphorylated PI3K/Akt/eNOS protein induced by FTA/PGSDS were markedly abolished by NG-nitro-L-arginine methyl ester (L-NA, eNOS inhibitor) and wortmannin (PI3K/AKT inhibitor), respectively, indicating an endothelium-dependent vasodilation via the PI3K/AKT-eNOS pathway (P<0.01). Conclusion: This study provides a strategy for rapidly and precisely elucidating GX II's representative in/ex vivo cardioprotective absorbed bioactive compounds (ABCs)-FTA, suggesting its potential in advancing precision ethnomedicine. [ABSTRACT FROM AUTHOR]

Background: Long-term exposure to a high altitude environment with low pressure and low oxygen could cause abnormalities in the structure and function of the heart. Myocardial strain is a sensitive indicator for assessing myocardial dysfunction, monitoring myocardial strain is of great significance for the early diagnosis and treatment of high altitude heart-related diseases. This study applies cardiac magnetic resonance tissue tracking technology (CMR-TT) to evaluate the changes in left ventricular myocardial function and structure in rats in high altitude environment. Methods: 6-week-old male rats were randomized into plateau hypoxia rats (plateau group, n = 21) as the experimental group and plain rats (plain group, n = 10) as the control group. plateau group rats were transported from Chengdu (altitude: 360 m), a city in a plateau located in southwestern China, to the Qinghai-Tibet Plateau (altitude: 3850 m), Yushu, China, and then fed for 12 weeks there, while plain group rats were fed in Chengdu(altitude: 360 m), China. Using 7.0 T cardiac magnetic resonance (CMR) to evaluate the left ventricular ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV), as well as myocardial strain parameters including the peak global longitudinal (GLS), radial (GRS), and circumferential strain (GCS). The rats were euthanized and a myocardial biopsy was obtained after the magnetic resonance imaging scan. Results: The plateau rats showed more lower left ventricular GLS and GRS (P < 0.05) than the plain rats. However, there was no statistically significant difference in left ventricular EDV, ESV, SV, EF and GCS compared to the plain rats (P > 0.05). Conclusions: After 12 weeks of exposure to high altitude low-pressure hypoxia environment, the left ventricular global strain was partially decreased and myocardium is damaged, while the whole heart ejection fraction was still preserved, the myocardial strain was more sensitive than the ejection fraction in monitoring cardiac function. [ABSTRACT FROM AUTHOR]

Introduction: P. candolleana Wight et Arn. Is a traditional Chinese herbal medicine used by the Gelao nationality in southwest China, has been historically applied to treat various gastrointestinal disorders. Despite its traditional usage, scientific evidence elucidating its efficacy and mechanisms in treating ulcerative colitis (UC) remains sparse. This study aimed to determine the quality and chemical composition of Pimpinella candolleana and to identify its potential therapeutic targets and mechanisms in acetic acid-induced ulcerative colitis (UC) rats through integrated approaches. Methods: Morphological and microscopic characteristics, thin layer chromatography (TLC) identification, and quantitative analysis of P. candolleana were performed. UPLC-Q-TOF-MS, network pharmacology, and molecular docking were used to identify its chemical composition and predict its related targets in UC. Furthermore, a rat model was established to evaluate the therapeutic effect and potential mechanism of P. candolleana on UC. Results: Microscopic identification revealed irregular and radial arrangement of the xylem in P. candolleana, with a light green cross-section and large medullary cells. UPLC-Q-TOF-MS analysis detected and analyzed 570 metabolites, including flavonoids, coumarins, and terpenoids. Network pharmacology identified 12 effective components and 176 target genes, with 96 common targets for P. candolleana-UC, including quercetin, luteolin, and nobiletin as key anti-inflammatory components. GO and KEGG revealed the potential involvement of their targets in RELA, JUN, TNF, IKBKB, PTGS2, and CHUK, with action pathways such as PI3K-Akt, TNF, IL-17, and apoptosis. Molecular docking demonstrated strong affinity and binding between these key components (quercetin, luteolin, and nobiletin) and the key targets of the pathway, including JUN and TNF. Treatment with P. candolleana improved body weight loss, the disease activity index, and colonic histological damage in UC rats. Pimpinella candolleana also modulated the levels of IL-2 and IL-6 in UC rats, reduced the expression of pro-inflammatory cytokines such as IL-6, MAPK8, TNF-a, CHUK, and IKBKB mRNA, and decreased the expression of TNF, IKBKB, JUN, and CHUK proteins in the colon of UC rats, thereby reducing inflammation and alleviating UC symptoms. Conclusion: P. candolleana exerts its protective effect on UC by reducing the expression of proinflammatory cytokines and inhibiting inflammation, providing scientific evidence for its traditional use in treating gastrointestinal diseases. This study highlights the potential of P. candolleana as a natural therapeutic agent for UC and contributes to the development of novel medicines for UC treatment. [ABSTRACT FROM AUTHOR]

Background: This study was designed to evaluate the effects of low-frequency electroacupuncture (EA) on glucose and lipid disturbances in a rat model of polycystic ovary syndrome (PCOS) characterized by insulin resistance (IR) and hepatic steatosis. Methods: The PCOS rat model was induced by continuous administration of letrozole (LET) combined with a high-fat diet (HFD). Female Sprague–Dawley rats were divided into the following four groups: control, control + EA, LET + HFD and LET + HFD + EA. EA was administered five or six times a week with a maximum of 20 treatment sessions. Body weight, estrous cyclicity, hormonal status, glucose and insulin tolerance, lipid profiles, liver inflammation factors, liver morphology and changes in the phosphatidylinositol 3-kinase (PI3-K)/Akt (protein kinase B) pathway were evaluated. Results: The rat model presented anovulatory cycles, increased body weight, elevated testosterone, abnormal glucose and lipid metabolism, IR, liver inflammation, hepatic steatosis and dysregulation of the insulin-mediated PI3-K/Akt signaling axis. EA reduced fasting blood glucose, fasting insulin, area under the curve for glucose, homeostasis model assessment of IR indices, triglycerides and free fatty acids, and alleviated hepatic steatosis. Furthermore, low-frequency EA downregulated mRNA expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6, upregulated mRNA expression of peroxisome proliferator-activated receptor (PPAR)-α, increased protein expression of phosphorylated (p)-Akt (Ser473), p-glycogen synthase kinase (GSK) 3β (Ser9) and glucose transporter 4 (GLUT4), increased the ratio of p-GSK3β to GSK3β and downregulated protein expression of GSK3β. Conclusion: An obese PCOS rat model with IR and hepatic steatosis was successfully established by the combination of LET and HFD. EA improved dysfunctional glucose and lipid metabolism in this PCOS-IR rat model, and the molecular mechanism appeared to involve regulation of the expression of key molecules of the PI3-K/Akt insulin signaling pathway in the liver. [ABSTRACT FROM AUTHOR]

Globally, Enterocytozoon bieneusi has been detected in humans and various animal hosts. Wild rats and shrews have the potential to act as carriers of E. bieneusi, facilitating the parasite's transmission to humans and domestic animals. We aimed to investigate the prevalence of E. bieneusi in 652 wild rats and shrews from Zhejiang Province, China, by amplifying the internal transcribed spacer (ITS) region of rDNA through polymerase chain reaction (PCR). To determine animal species, we amplified the Cytochrome b (Cyt-b) gene in their fecal DNA using PCR. Furthermore, we determined the genotype of E. bieneusi by amplifying the ITS region of rDNA through PCR. Genetic traits and zoonotic potential were evaluated using similarity and phylogenetic analyses. Suncus murinus (n = 282) and five rat species, Rattus losea (n = 18), Apodemus agrarius (n = 36), Rattus tanezumi (n = 86), Rattus norvegicus (n = 155), and Niviventer niviventer (n = 75), were identified. The average infection rate of E. bieneusi was 14.1% (92/652) with 18.1% (51/282) in S. murinus and 11.1% (41/370) in rats (27.8% in R. losea, 22.2% in A. agrarius, 10.5% in R. tanezumi, 8.4% in R. norvegicus, and 8.0% in N. niviventer). Thirty-three genotypes were identified, including 16 known genotypes. The most commonly known genotypes were HNR-VI (n = 47) and Peru11 (n = 6). Type IV, KIN-1, SHW7, and HNPL-II were each found in two samples, while Macaque4, CH5, K, Henan-III, Henan-V, HNP-II, HNPL-I, HNPL-III, HNHZ-II, and HNHZ-III were each found in one sample. Additionally, 17 novel genotypes were discovered: WZR-VIII (n = 5), WZR-I to WZR-VII, WZR-IX to WZR-XII, and WZSH-I to WZSH-V (n = 1 each). Those 33 genotypes were divided into three groups: Group 1 (n = 25), Group 2 (n = 3), and Group 13 (n = 5). The initial report underscores the extensive occurrence and notable genetic diversity of E. bieneusi in wild rats and shrews from Zhejiang province, China. These results suggest that these animals play a pivotal role in the transmission of E. bieneusi. Furthermore, animals carrying the zoonotic genotypes of E. bieneusi pose a serious threat to residents. [ABSTRACT FROM AUTHOR]

Thrombophlebitis is the inflammatory condition characterized by obstruction of one or more vessels, commonly in the legs, due to the formation of blood clots. It has been reported that traditional Chinese medicine, including Mailuoning injection, is advantageous for treating inflammatory and blood disorders. This research assessed the therapeutic efficacy of Mailuoning injection in the treatment of thrombophlebitis in rodents, as well as investigated its impact on fibrinolysis, inflammation, and coagulation. An experimental setup for thrombophlebitis was established in rodents via modified ligation technique. Five groups comprised the animals: sham operation group, model group, and three Mailuoning treatment groups (low, medium, and high dosages). The pain response, edema, coagulation parameters (PT, APTT, TT, FIB), serum inflammatory markers (IL‐6, TNF‐α, CRP), and expression levels of endothelial markers (ICAM‐1, VCAM‐1, NF‐κB) were evaluated. Blood flow and vascular function were further assessed by measuring hemorheological parameters and the concentrations of TXB2, ET, and 6‐k‐PGF1α. In contrast to the sham group, model group demonstrated statistically significant increases in endothelial expression levels, coagulation latencies, and inflammatory markers (p < 0.05). The administration of mailing, specifically at high and medium dosages, resulted in a substantial reduction in inflammatory markers, enhancement of coagulation parameters, suppression of ICAM‐1 and VCAM‐1 expression, and restoration of hemorheological measurements to baseline (p < 0.05). Significantly higher concentrations of 6‐k‐PGF1α and lower levels of TXB2 and ET were observed in high‐dose group, suggesting that pro‐ and anti‐thrombotic factors were restored to equilibrium. Utilization of Mailuoning injection in rat model of thrombophlebitis exhibited significant therapeutic impact. This effect was manifested through pain alleviation, diminished inflammation, enhanced blood viscosity and facilitation of fibrinolysis. The study indicated that Mailuoning injection may serve as a viable therapeutic option for thrombophlebitis, potentially aiding in the improvement of wound healing by virtue of its anti‐inflammatory and blood flow‐enhancing characteristics. [ABSTRACT FROM AUTHOR]

Background: The geographic distribution and host-parasite interaction networks of Sarcocystis spp. in small mammals in eastern Asia remain incompletely known. Methods: Experimental infections, morphological and molecular characterizations were used for discrimination of a new Sarcocystis species isolated from colubrid snakes and small mammals collected in Thailand, Borneo and China. Results: We identified a new species, Sarcocystis muricoelognathis sp. nov., that features a relatively wide geographic distribution and infects both commensal and forest-inhabiting intermediate hosts. Sarcocystis sporocysts collected from rat snakes (Coelognathus radiatus, C. flavolineatus) in Thailand induced development of sarcocysts in experimental SD rats showing a type 10a cyst wall ultrastructure that was identical with those found in Rattus norvegicus from China and the forest rat Maxomys whiteheadi in Borneo. Its cystozoites had equal sizes in all intermediate hosts and locations, while sporocysts and cystozoites were distinct from other Sarcocystis species. Partial 28S rRNA sequences of S. muricoelognathis from M. whiteheadi were largely identical to those from R. norvegicus in China but distinct from newly sequenced Sarcocystiszuoi. The phylogeny of the nuclear 18S rRNA gene placed S. muricoelognathis within the so-called S. zuoi complex, including Sarcocystisattenuati, S. kani, S. scandentiborneensis and S. zuoi, while the latter clustered with the new species. However, the phylogeny of the ITS1-region confirmed the distinction between S. muricoelognathis and S. zuoi. Moreover, all three gene trees suggested that an isolate previously addressed as S. zuoi from Thailand (KU341120) is conspecific with S. muricoelognathis. Partial mitochondrial cox1 sequences of S. muricoelognathis were almost identical with those from other members of the group suggesting a shared, recent ancestry. Additionally, we isolated two partial 28S rRNA Sarcocystis sequences from Low's squirrel Sundasciurus lowii that clustered with those of S. scandentiborneensis from treeshews. Conclusions: Our results provide strong evidence of broad geographic distributions of rodent-associated Sarcocystis and host shifts between commensal and forest small mammal species, even if the known host associations remain likely only snapshots of the true associations. [ABSTRACT FROM AUTHOR]

Bitespiramycin, has been shown to have a therapeutic effect against respiratory tract inflammation, including a potential effect against COVID-19. A current clinical trial in China showed that bitespiramycin was an effective treatment for severe pneumonia and intracranial infection. However, there is lack of an analytical method to elucidate the distribution of bitespiramycin. In this study, a highly sensitive, rapid and reliable UPLC–MS/MS method was developed to comprehensively characterize the bitespiramycin distribution in various bio-samples, which is significantly improved upon the published work. A rapid sample preparation method was developed by using n-butanol as the solvent to extract bitespiramycin from different bio-samples. The extract was then directly analyzed by UPLC–MS/MS coupled with an alkaline-resistant column after centrifugation which avoids the time-consuming concentration process under nitrogen and redissolution. The method was employed to accurately quantify bitespiramycin and its metabolites in rat plasma, tissues, and human cerebrospinal fluid. Notably, the presence of bitespiramycin and its metabolites was identified for the first time in various rat organs including brain, testis, bladder and prostate as well as in human cerebrospinal fluid. This newly developed approach shows great promise for drug distribution assays including other antibiotics and can help elucidate the ADME of bitespiramycin. [ABSTRACT FROM AUTHOR]

Introduction: Takotsubo cardiomyopathy (TTC), also known as stress‐induced cardiomyopathy, resembles acute heart failure syndrome but lacks disease‐specific diagnosis and treatment strategies. TTC accounts for approximately 5–6% of all suspected cases of acute coronary syndrome in women. At present, animal models of TTC are often created by large amounts of exogenous catecholamines such as isoproterenol. However, isoproterenol injection cannot fully simulate the onset of stress‐induced cardiomyopathy in humans since stress is not an instantaneous event. Methods: Rats were immobilized for 6 h per day for 1–14 days. To examine whether the TTC model was successful, echocardiography was employed; Elisa detected serum sympathetic activation markers; and the Open‐Field test (OFT) was used to analyze behavioral changes in rats after stress. Western blot and histology were used to assess sympathetic remodeling, inflammation levels, and fibrosis; qRT‐PCR was used to explore the levels of fibrosis and myocardial hypertrophy. The electrical stability of ventricular was determined by electrophysiological testing. Results: The rats showed severe stress behavior and local sympathetic remodeling of the heart after only 1 day of stress. After 3 days of stress, the induction of ventricular tachyarrhythmia increased prominently. The highest incidence of TTC in rats was at 5 days of immobilization stress. The pathological left ventricular remodeling caused by immobilization (IMO) stress includes inflammatory infiltration, fibrosis, and myocardial hypertrophy. Conclusions: Our study confirms the hypothesis that IMO stress can mimic Takotsubo cardiomyopathy, and the various effects on the heart depending on the duration of IMO stress. We observed the highest incidence of TTC occurred after 5 days of stress. Furthermore, there is a gradual occurrence of electrical and structural remodeling as the stress duration prolongs. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the effects of electroacupuncture (EA) on cognitive recovery and synaptic remodeling in a rat model of middle cerebral artery occlusion (MCAO) followed by reperfusion and explore the possible mechanism. Method: Focal cerebral ischemia was modeled in healthy adult Sprague-Dawley rats by MCAO. The MCAO rats were classified into four groups: sham, MCAO, MCAO + GB20 (receiving EA at GB20) and MCAO + NA (receiving EA at a "non-acupoint" location not corresponding to any traditional acupuncture point location about 10 mm above the iliac crest). Neurological deficit scores and behavior were assessed before and during the treatment. After intervention for 7 days, the hippocampus was dissected to analyze growth-associated protein (GAP)-43, synaptophysin (SYN) and postsynaptic density protein (PSD)-95 expression levels by Western blotting. Bioinformatic analysis and primary hippocampal neurons with calcium-voltage gated channel subunit alpha 1B (CACNA1B) gene overexpression were used to screen the target genes for EA against MCAO. Results: Significant amelioration of neurological deficits and learning/memory were found in MCAO + GB20 rats compared with MCAO or MCAO + NA rats. Protein levels of GAP-43, SYN and PSD-95 were significantly improved in MCAO + GB20–treated rats together with an increase in the number of synapses in the hippocampal CA1 region. CACNA1B appeared to be a target gene of EA in MCAO. There were increased mRNA levels of CACNA1B, calmodulin (CaM), Ca2+/calmodulin-dependent protein kinase type II (CaMKII) and cyclic adenosine monophosphate response element binding (CREB) and increased phosphorylation of CaM, CaMKII and CREB in the hippocampal region in MCAO + GB20 versus MCAO and MCAO + NA groups. CACNA1B overexpression modulated expression of the CaM–CaMKII–CREB axis. Conclusion: EA treatment at GB20 may ameliorate the negative effects of MCAO on cognitive function in rats by enhancing synaptic plasticity. EA treatment at GB20 may exert this neuroprotective effect by regulating the CACNA1B–CaM–CaMKII–CREB axis. [ABSTRACT FROM AUTHOR]

Background: Penthorum chinense Pursh (PCP) is widely utilized in China to treat a variety of liver diseases. It has been shown that flavonoids inhibit inflammation and have the potential to attenuate tissue damage and fibrosis. However, the mechanisms underlying how total flavonoids isolated from PCP (TFPCP) exert their anti-fibrotic effects remain unclear. Methods: The chemical composition of TFPCP was determined using UHPLC–QOrbitrap HRMS. Subsequently, rats were randomly assigned to a control group (Control), a carbon tetrachloride (CCl4)-induced hepatic fibrosis model group (Model), a positive control group [0.2 mg/(kg·day)] of Colchicine), and three TFPCP treatment groups [50, 100, and 150 mg/(kg·day)]. All substances were administered by gavage and treatments lasted for 9 weeks. Simultaneously, rats were intraperitoneally injected with 10%–20% CCl4 for 9 weeks to induce liver fibrosis. At the end of the experiment, the liver ultrasound, liver histomorphological, biochemical indicators, and inflammatory cytokine levels were tested respectively. The underlying mechanisms were assessed using Western blot, immunohistochemistry, immunofluorescence, RT-qPCR, and metabolomics. Results: Fourteen flavonoids were identified in TFPCP. Compared with control animals, CCl4-treated rats demonstrated obvious liver injury and fibrosis, manifested as increases in gray values, distal diameter of portal vein (DDPV) and a decrease in blood flow velocity (VPV) in the ultrasound analysis; increased biochemical index values (serum levels of ALT, AST, TBIL, and ALP); marked increases in the contents of fibrotic markers (PC III, COL4, LN, HA) and inflammatory factors (serum TNF-α, IL-6, and IL-1β); and significant pathological changes. However, compared with the Model group, the ultrasound parameters were significantly improved and the serum levels of inflammatory cytokines were reduced in the TFPCP group. In contrast, the expression of TGF-β1, TLR4, and MyD88, as well as the p-P65/P65 and p-IκBα/IκBα ratios, were considerably reduced following TFPCP treatment. In addition, we identified 32 metabolites exhibiting differential abundance in the Model group. Interestingly, TFPCP treatment resulted in the restoration of the levels of 20 of these metabolites. Conclusion: Our findings indicated that TFPCP can ameliorate hepatic fibrosis by improving liver function and morphology via the inactivation of the TLR4/MyD88- mediated NF-κB pathway and the regulation of liver metabolism. [ABSTRACT FROM AUTHOR]

Background: This study investigated the effect of uteroplacental insufficiency (UPI) on renal development by detecting metabolic alterations in the kidneys of rats with intrauterine growth restriction (IUGR). Methods: On gestational day 17, pregnant Sprague Dawley rats were selected and allocated randomly to either the IUGR group or the control group. The IUGR group received a protocol involving the closure of bilateral uterine vessels, while the control group underwent a sham surgery. The rat pups were delivered on gestational day 22 by natural means. Pups were randomly recruited from both the control and IUGR groups on the seventh day after birth. The kidneys were surgically removed to conduct Western blot and metabolomic analyses. Results: IUGR was produced by UPI, as evidenced by the significantly lower body weights of the pups with IUGR compared to the control pups on postnatal day 7. UPI significantly increased the levels of cleaved caspase-3 (p < 0.05) and BAX/Bcl-2 (p < 0.01) in the pups with IUGR. Ten metabolites exhibited statistically significant differences between the groups (q < 0.05). Metabolic pathway enrichment analysis demonstrated statistically significant variations between the groups in the metabolism related to fructose and mannose, amino and nucleotide sugars, and inositol phosphate. Conclusions: UPI alters kidney metabolism in growth-restricted newborn rats and induces renal apoptosis. The results of our study have the potential to provide new insights into biomarkers and metabolic pathways that are involved in the kidney changes generated by IUGR. [ABSTRACT FROM AUTHOR]

Cardamine circaeoides Hook.f. & Thomson (CC), a herb of the genus Cardamine (family Brassicaceae), has a rich historical usage in China for both culinary and medicinal purposes. It is distinguished by its remarkable ability to hyperaccumulate selenium (Se). CC has demonstrated efficacy in the prevention of metabolic disorders. However, investigations into the effects of CC on asymptomatic hyperuricemia remain scarce. The objective of this study is to elucidate the mechanism by which CC aqueous extract (CCE) exerts its anti-hyperuricemic effects on asymptomatic hyperuricemic rats induced by potassium oxonate (PO) by integratingmetabolomics and network pharmacological analysis. Asymptomatic hyperuricemia was induced by feeding rats with PO (1000mg/kg) and CCE (0.75, 1.5, or 3 g/kg) once daily for 30 days. Various parameters, including bodyweight, uric acid (UA) levels, histopathology of renal tissue, and inflammatory factors (IL-1β, IL-6, IL-8, and TNF-α) were assessed. Subsequently, metabolomic analysis of kidney tissues was conducted to explore the effects of CCE on renal metabolites and the related pathways. Furthermore, network pharmacology was employed to explicate themechanism of action of CCE components identified through UPLC-Q-TOF-MS analysis. Finally, metabolomic and network-pharmacology analyses were performed to predict crucial genes dysregulated in the disease model and rescued by CCE, which were then subjected to verification by RT-qPCR. The findings revealed that CCE significantly inhibited the UA levels from the 21st day to the 30th day. Moreover, CCE exhibited significant inhibition of IL-1β, IL-6, IL-8, and TNF-α levels in renal tissues. The dysregulation of 18 metabolites and the tyrosine, pyrimidine, cysteine, methionine, sphingolipid, and histidine metabolism pathways was prevented by CCE treatment. A joint analysis of targets predicted using the network pharmacology approach and the differentialmetabolites found in metabolics predicted 8 genes as potential targets of CCE, and 3 of them(PNP gene, JUN gene, and ADA gene) were verified at the mRNA level by RT-qPCR. We conclude that CCE has anti-hyperuricemia effects and alleviates renal inflammation in a rat model of hyperuricemia, and these efficacies are associated with the reversal of increased ADA, PNP, and JUN mRNA expression in renal tissues. [ABSTRACT FROM AUTHOR]

Hemorrhagic shock (HS) is the leading cause of death in trauma patients. Inflammation following HS can lead to cardiac damage. Pachymic acid (PA), a triterpenoid extracted from Poria cocos, has been found to possess various biological activities, including anti-inflammatory and anti-apoptotic properties. Our research aims to investigate the protective effects of PA against HS-induced heart damage and the underlying mechanisms involved. Male Sprague-Dawley rats were intraperitoneally injected with PA (7.5 or 15 mg/kg) daily for three days. Subsequently, we created a rat model of HS by drawing blood through a catheter inserted into the femoral artery followed by resuscitation. The results revealed that HS led to abnormalities in hemodynamics, serum cardiac enzyme levels, and cardiac structure, as well as induced cardiac apoptosis. However, pretreatment with PA effectively alleviated these effects. PA-pretreatment also suppressed mRNA and protein levels of interleukin (IL)-1 β , IL-6, and tumor necrosis factor α (TNF- α) in the heart tissues of HS rats. Additionally, PA-pretreatment reduced inflammatory cell infiltration and M1 macrophage polarization while exaggerating M2 polarization in HS rat hearts. The study observed a decreased proportion of the expression of of M1 macrophages (CD86 + ) and their marker (iNOS), along with an increased proportion of the expression of M2 macrophages (CD206 + ) and their marker (Arg-1). Notably, PA-pretreatment suppressed NF- κ B pathway activation via inhibiting NF- κ B p65 phosphorylation and its nuclear translocation. In conclusion, PA-pretreatment ameliorates HS-induced cardiac injury, potentially through its inhibition of the NF- κ B pathway. Therefore, PA treatment holds promise as a strategy for mitigating cardiac damage in HS. [ABSTRACT FROM AUTHOR]

Astragalus membranaceus is a traditional Chinese medicine derived from the roots of Astragalus membranaceus (Fisch.) Bge., which has the same medicinal and edible uses in China. It is also widely used in daily food, and its pharmacological effects mainly include antioxidant effects, vascular softening effects, etc. Currently, it is increasingly widely used in the prevention of hypertension, cerebral ischemia, and stroke in China. Formononetin and its glucopyranoside (ononin) are both important components of Astragalus membranaceuss and may play important roles in the treatment of cardiovascular diseases (CVDs). This study conducted metabolic studies using formononectin and its glucopyranoside (ononin), including a combination of the in vitro metabolism of Formonetin using rat liver S9 and the in vivo metabolism of ononin administered orally to rats. Five metabolites (Sm2, 7, 9, 10, and 12) were obtained from the solution incubated with formononetin and rat hepatic S9 fraction using chromatographic methods. The structures of the five metabolites were elucidated as (Sm2)6,7,4′-trihydroxy-isoflavonoid; (Sm7)7,4′-dihydroxy-isoflavonoid; (Sm9)7,8,4′-trihydroxy-isoflavonoid; (Sm10)7,8,-dihydroxy-4′-methoxy-isoflavonoid; and (Sm12)6,7-dihydroxy-4′-methoxy- isoflavonoid on the basis of UV, NMR, and MS data. Totally, 14 metabolites were identified via HPLC-DAD-ESI-IT-TOF-MSn analysis, from which the formononetin was incubated with rat hepatic S9 fraction, and the main metabolic pathways were hydroxylation, demethylation, and glycosylation. Then, 21 metabolites were identified via HPLC-DAD-ESI-IT-TOF-MSn analysis from the urine samples from SD rats to which ononin was orally administered, and the main metabolic pathways were glucuronidation, hydroxylation, demethylation, and sulfonation. The main difference between the in vitro metabolism of formononetin and the in vivo metabolism of ononin is that ononin undergoes deglycemic transformation into Formonetin in the rat intestine, while Formonetin is absorbed into the bloodstream for metabolism, and the metabolic products also produce combined metabolites during in vivo metabolism. The six metabolites obtained from the aforementioned separation indicate the primary forms of formononetin metabolism, and due to their higher contents of similar isoflavone metabolites, they are considered the main active compounds that are responsible for pharmacological effects. To investigate the metabolites of the active ingredients of formononetin in the rat liver S9 system, network pharmacology was used to evaluate the cardiovascular disease (CVD) activities of the six primary metabolites that were structurally identified. Additionally, the macromolecular docking results of six main components and two core targets (HSP90AA1 and SRC) related to CVD showed that formononetin and its main metabolites, Sm10 and Sm12, may have roles in CVD treatment due to their strong binding activities with the HSP90AA1 receptor, while the Sm7 metabolite may have a role in CVD treatment due to its strong binding activity with the SRC receptor. [ABSTRACT FROM AUTHOR]

As a group of ectoparasites, chiggers (larvae of chigger mites) are the exclusive vector of scrub typhus (tsutsugamushi disease). Rodents are the most important hosts of chiggers. The Anderson's niviventer rat, Niviventer andersoni, is an endemic species of rodent in China. However, few studies have involved this endemic rodent species and its ectoparasites including chiggers. According to the field investigation in five provincial regions of southwest China between 2001 and 2019, this paper retrospectively analysed the infestation and distribution of chiggers on the body surface of N. andersoni in southwest China for the first time. From 77 Anderson's niviventer rats captured, a total of 527 chiggers were collected and they were identified as 39 species and nine genera in two subfamilies of family Trombiculidae. Of 39 chigger species identified, Leptotrombidium deliense and L. scutellare are the most important vectors of scrub typhus in China. The overall infestation indexes were PM = 29.87%, MA = 6.84 and MI = 22.91, and the indexes of chigger mite community were Mf = 39, H' = 2.60, E = 0.71 and D = 0.12. The dominant chigger species are L. wenense, L. xiaguanense and L. fujianense with a total Cr = 51.04%, among which L. wenense is one of the six main vectors of scrub typhus in China. The dominant chigger species are of aggregated distribution among different individuals of the rats. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a catastrophic condition with few therapeutic options. Astaxanthin (AST), a natural nutritional supplement with powerful antioxidant activities, is finding its new application in the field of SCI. Here, we performed a systematic review to assess the neurological roles of AST in rats following SCI, and assessed the potential for clinical translation. Searches were conducted on PubMed, Embase, Cochrane Library, the Web of Science, China National Knowledge Infrastructure, WanFang data, Vip Journal Integration Platform, and SinoMed databases. Animal studies that evaluated the neurobiological roles of AST in a rat model of SCI were included. A total of 10 articles were included; most of them had moderate-to-high methodological quality, while the overall quality of evidence was not high. Generally, the meta-analyses revealed that rats treated with AST exhibited an increased Basso, Beattie, and Bresnahan (BBB) score compared with the controls, and the weighted mean differences (WMDs) between those two groups showed a gradual upward trend from days 7 (six studies, n = 88, WMD = 2.85, 95% CI = 1.83 to 3.87, p < 0.00001) to days 28 (five studies, n = 76, WMD = 6.42, 95% CI = 4.29 to 8.55, p < 0.00001) after treatment. AST treatment was associated with improved outcomes in spared white matter area, motor neuron survival, and SOD and MDA levels. Subgroup analyses indicated there were differences in the improvement of BBB scores between distinct injury types. The trial sequential analysis then firmly proved that AST could facilitate the locomotor recovery of rats following SCI. In addition, this review suggested that AST could modulate oxidative stress, neuroinflammation, neuron loss, and autophagy via multiple signaling pathways for treating SCI. Collectively, with a protective effect, good safety, and a systematic action mechanism, AST is a promising candidate for future clinical trials of SCI. Nonetheless, in light of the limitations of the included studies, larger and high-quality studies are needed for verification. [ABSTRACT FROM AUTHOR]

Preserved eggs are traditional alkali‐pickled food in China and have been enjoyed by consumers and extensively studied by researchers for their nutritional tastes and their anti‐tumor, anti‐inflammatory, antioxidant, lipid‐lowering, and blood pressure‐lowering properties. To study the anti‐tumor effects of preserved eggs, this project observed the health on rats, and anti‐tumor effects and separated anti‐tumor active components on HT‐29 cells. SD rats fed for 80 days showed that preserved eggs had no significant effect on weight, food intake, blood pH, liver tissues, or organ indices. Preserved eggs significantly increased blood levels of oxidative stress markers SOD and CAT, decreased MDA levels by 0.46, 0.23, and 0.25 times. Moreover, they also increased the level of IL‐2 from 1233 to 1340 pg/mL. Two water‐soluble bioactive peptide fractions, B1 and B2, with molecular weights ≥10 kDa were further obtained from preserved eggs by ultrafiltration and Superdex Peptide 10/300 GL. The potential mechanism of B1 and B2 is to activate the internal mitochondrial apoptotic pathway and induce apoptosis by up‐regulating the expression of the pro‐apoptotic factors cytochrome C, caspase‐3, and caspase‐9 mRNA in HT‐29 cells. [ABSTRACT FROM AUTHOR]

Background and objective Currently, a significant number of miners are involved in mining operations at the Gejiu tin mine in Yunnan. This occupational setting is associated with exposure to dust particles, heavy metals, polycyclic aromatic hydrocarbons, and radioactive radon, thereby significantly elevating the risk of lung cancer. This study aims to investigate the involvement of leptin-mediated extracellular regulated protein kinase (ERK) signaling pathway in the malignant transformation of rat alveolar type II epithelial cells induced by Yunnan tin mine dust. Methods Immortalized rat alveolar cells type II (RLE-6TN) cells were infected with Yunnan tin mine dust at a concentration of 200 μg/mL for nine consecutive generations to establish the infected cell model, which was named R200 cells. The cells were cultured normally, named as R cells. The expression of leptin receptor in both cell groups was detected using the Western blot method. The optimal concentration of leptin and mitogen-activated protein kinase kinase (MEK) inhibitor (U0126) on R200 cells was determined using the MTT method. Starting from the 20th generation, the cells in the R group were co-cultured with leptin, while the cells in the R200 group were co-cultured with the MEK inhibitor U0126. The morphological alterations of the cells in each group were visualized utilizing hematoxylin-eosin staining. Additionally, concanavalin A (ConA) was utilized to detect any morphological differences, and an anchorage-independent growth assay was conducted to assess the malignant transformation of the cells. The changes in the ERK signaling pathway in epithelial cells after the action of leptin were detected using the Western blot method. Results Both the cells in the R group and R200 group express leptin receptor OB-R. Compared to the R200 group, the concentration of leptin at 100 ng/mL shows the most significant pro-proliferation effect. The proliferation of R200 cells infected with the virus is inhibited by 30 μmol/L U0126, and a statistically significant divergence was seen when compared to the control group (P<0.05). Starting from the 25th generation, the cell morphology of the leptin-induced R200 group (R200L group) underwent changes, leading to malignant transformation observed at the 30th generation. The characteristics of malignant transformation became evident by the 40th generation in the R200L group. In contrast, the other groups showed agglutination of P40 cells, and the speed of cell aggregation increased with an increase in ConA concentration. Notably, the R200L group exhibited faster cell aggregation compared to the U0126-induced R200 (R200LU) group. Additionally, the cells in the R200L group were capable of forming clones starting from P30, with a colony formation rate of 2.25‰±0.5‰. However, no clonal colonies were observed in the R200LU group and R200 group. The expression of phosphorylated extracellular signal-regulated kinase (pERK) was enhanced in cells of the R200L group. However, when the cells in the R200L group were treated with U0126, a blocking agent, the phosphorylation level of pERK decreased. Conclusion Leptin can promote the malignant transformation of lung epithelial cells infected by mine dust, and the ERK signaling pathway may be necessary for the transformation of alveolar type II epithelial cells induced by Yunnan tin mine dust. [ABSTRACT FROM AUTHOR]

Total saponins from Trillium tschonoskii Maxim (TSTT), a bioactive component of local natural herbs in the Enshi area, China, have been demonstrated to have functions of restoring cognitive capacity and promoting axonal regeneration post-stroke, but the mechanism of this process remains unclear. The hippocampus is a critical tissue for controlling learning and memory capacity, and the sonic hedgehog (Shh) signaling pathway plays a major role in the patterning and synaptic plasticity of hippocampal neural circuits. Therefore, we aimed to investigate whether TSTT could restore learning and cognitive functions by modulating the Shh pathway in rats with post-stroke cognitive impairment (PSCI). The ischemia model was established by permanent middle cerebral artery occlusion (MCAO) in 100 Sprague-Dawley (SD) rats, and the model rats were administered using TSTT (100 mg/kg) or donepezil hydrochloride as the positive control (daily 0.45 mg/kg, DON) for 4 weeks after the operation. As assessed by the Morris water maze test, the cognitive function of PSCI rats was significantly improved upon TSTT treatment. Meanwhile, the cerebral infarct volume reduced with TSTT, as shown by HE and TTC staining, and the number of Nissl bodies and dendritic spine density were significantly increased, as shown by Nissl and Golgi staining. In addition, TSTT upregulated PSD-95, SYN, and GAP-43, and inhibited neuronal apoptosis, as evidenced by increased Bcl-2 levels along with decreased Bax and caspase-3 expression. TSTT could also significantly upregulate Shh, Ptch1, Smo, and Gli1 proteins, indicating the activation of the Shh signaling pathway. Therefore, TSTT can protect PSCI rats by inhibiting apoptosis and promoting neuronal synaptic remodeling. The Shh pathway is also involved. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of the aryl hydrocarbon receptor (AHR)/regulatory T cell (Treg)/T‐helper 17 (Th17) cell pathway on the pathogenesis of migraine. Background: Migraine is a disabling neurovascular disease that imposes an enormous burden on both individuals and society. The pathophysiological mechanisms of migraine remain controversial. Recent studies have suggested that immune dysfunction may be involved in the pathogenesis of migraine. The AHR, a receptor expressed on most immune cells, has been implicated in the occurrence of many autoimmune diseases; however, whether it is involved in the pathogenesis of migraine is unclear. Methods: A chronic migraine rat model was established through repeated intraperitoneal injection of nitroglycerin (NTG). The mechanical and thermal pain thresholds were assessed using von Frey filaments and radiant heat. Next, the protein expression levels of AHR in the trigeminal nucleus caudalis (TNC) region of chronic migraine (CM)‐like rats were quantified and the changes in Treg/Th17‐related transcription factors and inflammatory factors in the TNC were explored. To determine the role of AHR in CM, we examined the effects of the AHR agonist 2‐(1′‐indole‐3′‐carbonyl)‐thiazole‐4‐carboxylic acid methyl ester (ITE), and AHR antagonist CH‐223191 on pain behavior, c‐Fos, calcitonin gene‐related peptide (CGRP), AHR, and Treg/Th17‐related factor expression in CM‐like rats. Results: Repeated administration of NTG significantly enhanced nociceptive hypersensitivity and increased expression of c‐Fos and CGRP in rats, while AHR was significantly decreased in the TNC. In addition, the expression of the transcription factor forkhead box protein P3 and the signal transducer and activator of transcription 5 decreased significantly. In contrast, the expression of the transcription factor retinoic acid receptor‐related orphan receptor γ t and signal transducer and activator of transcription 3 were significantly increased. Moreover, the mRNA level of transforming growth factor beta‐1 was decreased, while that of interleukin (IL)‐10 and IL‐22 was increased in the TNC. The AHR agonist ITE alleviated migraine‐like pain behaviors in rats, activated the AHR signaling pathway, and improved the imbalance of Treg/Th17‐related transcription factors and inflammatory factors. Conversely, the AHR antagonist CH‐223191 did not alleviate migraine‐like pain behaviors in rats; and even exacerbated them. Conclusions: The AHR participates in the development of CM by regulating Treg/Th17‐related homeostasis. Therefore, treatments targeting the AHR/Treg/Th17 signaling pathway could be new effective interventions for CM treatment. [ABSTRACT FROM AUTHOR]

Paederia scandens (Lour.) Merr. (P. scandens), as an edible and medicinal herb, is commonly used for treating gastric ulcer in China; however, its mechanistic and effective substances' studies remain limited. This study aimed to investigate the antigastric ulcer effects of aqueous extracts of P. scandens (PS-AE) and explore the involvement of NF-κB signaling in this effect. In addition, the study aimed to identify the effective substances by exploring NF-κB inhibitors. The main components of PS-AE were identified using an UPLC-MS method. HCl/EtOH-induced acute gastric ulcer in rats, and LPS-stimulated RAW264.7 cells were used to determine the antigastric ulcer effects of PS-AE in vivo and in vitro, respectively. Histopathological changes of the ulcer tissues were observed using staining methods of HE and PAS; secretions of inflammatory cytokines and oxidative stress indexes were measured using biochemical test kits; protein levels of NF-κB signaling pathway-related molecules were measured using Western Blot. NF-κB inhibitors' identification in P. scandens was performed by developing HipHop pharmacophore model, and the results were further validated by molecular docking. In vivo, PS-AE significantly attenuated gastric ulcer in rats; reduced inflammation by adjusting the inflammatory cytokines TNF-α, IL-1β, and IL-6 levels; and induced oxidative stress can be alleviated via adjusting the levels of SOD, MDA, and GSH-Px. In addition, PS-AE may play an anti-inflammatory role mainly through NF-κB signaling pathway. Following pharmacophore modeling and molecular docking, 13 potential inhibitors targeting NF-κB were identified. In addition, in vitro, PS-AE and paederoside could significantly inhibit the activation of NF-κB p65 and the productions of downstream cytokines including NO, TNF-α, and IL-6. PS-AE protective effects on gastric ulcer damage induced by HCl/EtOH in rats, which is probably associated with its antioxidant effect and the inhibitory effects on levels of inflammatory mediators regulated by NF-κB signaling pathway. 13 potential NF-κB-targeting inhibitors are probably effective substances contributing to the herb's pharmacological effect. In practical application, Paederia scandens, a traditional food and medicinal plant, possessed diversified chemical components and multiple pharmacological activities (anti-inflammatory, bacteriostasis, and antioxidative.). In China, P. scandens has been used as a traditional medicine to treat gastritis for hundreds of years, and it may be a potentially effective dietary product to improve gastric ulcer. This study shows that P. scandens exerts protective effects on gastric ulcer damage induced by HCl/EtOH in rats, which is probably associated with its antioxidant effect and the inhibitory effects on levels of inflammatory mediators regulated by NF-κB signaling pathway, which provides pharmacological justifications for the functional food use of P. scandens for treating gastric disease. [ABSTRACT FROM AUTHOR]

Objective: Hypoxia can promote stem cell proliferation and migration through HIF-1α. Hypoxia can regulate cellular endoplasmic reticulum (ER) stress. Some studies have reported the relationship among hypoxia, HIF-α, and ER stress, however, while little is known about HIF-α and ER stress in ADSCs under hypoxic conditions. The purpose of the study was to investigate the role and relationship of hypoxic conditions, HIF-1α and ER stress in regulating adipose mesenchymal stem cells (ADSCs) proliferation, migration, and NPC-like differentiation. Method: ADSCs were pretreated with hypoxia, HIF-1α gene transfection, and HIF-1α gene silence. The ADSCs proliferation, migration, and NPC-like differentiation were assessed. The expression of HIF-1α in ADSCs was regulated; then, the changes of ER stress level in ADSCs were observed to investigate the relationship between ER stress and HIF-1α in ADSCs under hypoxic conditions. Result: The cell proliferation and migration assay results show that hypoxia and HIF-1α overexpression can significantly increase the ADSCs proliferation and migration, while HIF-1α inhibition can significantly decrease the ADSCs proliferation and migration. The HIF-1α and co-cultured with NPCs played an important role in the directional differentiation of ADSCs into NPCs. The hypoxia-regulated ER stress in ADSCs through the HIF-1α pathway, thereby regulating the cellular state of ADSCs, was also observed. Conclusion: Hypoxia and HIF-1α play important roles in proliferation, migration, and NPC-like differentiation of ADSCs. This study provides preliminary evidence that HIF-1α-regulated ER stress thus affects ADSCs proliferation, migration, and differentiation. Therefore, HIF-1α and ER may serve as key points to improve the efficacy of ADSCs in treating disc degeneration. [ABSTRACT FROM AUTHOR]

Objectives: This study was designated to establish a polycystic ovary syndrome (PCOS) rat model with recombinant human insulin-like growth factor-1 (RH-IGF-1). We made assessment on the characteristics of hyperinsulinemia and hyperandrogenism in the rat model. Design: This study performed the characteristics of PCOS upon RH-IGF-1 injection and evaluated the disease process of PCOS syndrome caused by the insulin-resistant pathological condition of IGF-1 based on the comparative study of in vivo test. Setting: The experiment was conducted in the experimental research center of Yinzhou NO.2 hospital, Ningbo, Zhejiang Province, China. Materials and Methods: Thirty-four female Sprague Dawley immature rats aged 21 days were randomly divided into two groups. Those treated with RH-IGF-1 2 mg/100 g daily were in RH-IGF-1 group (n = 20), and those with 0.9% sodium chloride 0.2 mL/100 g daily were in the saline group (n = 14). The experiment was carried out in two stages. In stage I, rats were anesthetized upon the first estrous cycle in the saline group with tissue and blood samples collected (n = 7), and rats in the RH-IGF-1-treated group were anesthetized on the 5th day after vaginal opening (VO) (n = 10). In stage II, rats in the saline group were anesthetized after three complete cycles (n = 7), meanwhile, while on the 15th day after VO (n = 10) for those in the RH-IGF-1 group. Results: We have found that compared with the control group, rats injected with RH-IGF-1 expressed an early VO, disordered estrous cycle, polycystic ovaries, and significantly increased ovarian weight/body weight ratio. And from the perspective of hormone secretion, their androgen increased significantly and the insulin resistance index also elevated distinctly, possessing main characteristics similar to PCOS. Limitations: In this study, we were limited by the inability to examine IGF-1 in hypothalamus. IGF-1 in hypothalamus and in vitro experiments would be taken into consideration for further study in the future. Conclusions: These findings suggest that IGF-1 may be a key factor in the pathogenesis of PCOS, and the increase of androgen may be the pathological result, not the cause of PCOS. [ABSTRACT FROM AUTHOR]

Simple Summary: The spatiotemporal interactions between predators and their prey can be largely changed by livestock encroachment. Using camera trapping technology, we found that the two prey guilds with contrasting diel activities, nocturnal rats and diurnal squirrels, showed different habitat preferences with their predator, leopard cats (Prionailurus bengalensis). We also found that the fine-scale spatiotemporal use of leopard cats was consistent and highly correlated with that of nocturnal rats under livestock disturbance. Our results indicate that livestock disturbance could modify the site-use and temporal activities between leopard cats and their prey. Habitat use and the temporal activities of wildlife can be largely modified by livestock encroachment. Therefore, identifying the potential impacts of livestock on the predator–prey interactions could provide essential information for wildlife conservation and management. From May to October 2017, we used camera trapping technology to investigate fine-scale spatiotemporal interactions in a predator–prey system with the leopard cat (Prionailurus bengalensis) as a common mesopredator, and its prey with contrasting activity patterns (i.e., nocturnal rats and diurnal squirrels) in a livestock-dominated nature reserve in Northern China. We found that the prey species showed different habitat preferences with the leopard cats. The nocturnal rats had strong positive effects on the site-use of the leopard cats, while the influence of livestock on the diurnal squirrels' site-use changed from strong positive effects to weak effects as the livestock disturbance increased. The temporal overlap between the leopard cats and the nocturnal rats was almost four times that of the leopard cats and the diurnal squirrels, regardless of the livestock disturbance. Our study demonstrated that the fine-scale spatiotemporal use patterns of the leopard cats were consistent and highly correlated with the nocturnal rats under livestock disturbance. We suggest that appropriate restrictions on livestock disturbance should be implemented by reserve managers to reduce the threat to wildlife and achieve multi-species coexistence. [ABSTRACT FROM AUTHOR]

Background: Porcine circovirus type 2 (PCV2) has caused great economic losses in the global pig industry. There have been published records of wild rats acting as the reservoirs of PCV2 (only PCV2a and PCV2b), but almost all of which were related to the PCV2-infected swine herds. Results: In this study, we carried out the detection, amplification, and characterization of novel PCV2 strains in wild rats that were captured far from pig farms. Nested PCR assay demonstrated that the kidney, heart, lung, liver, pancreas, and large and small intestines of rats were screened positive for PCV2. We subsequently sequenced two full genomes of PCV2 in positive sample pools, designated as js2021-Rt001 and js2021-Rt002. Genome sequence analysis indicated that they had the highest similarity to nucleotide sequences of porcine-origin PCV2 isolates in Vietnam. Phylogenetically, js2021-Rt001 and js2021-Rt002 were a part of the PCV2d genotype cluster, which is a predominant genotype circulating worldwide in recent years. The antibody recognition regions, immunodominant decoy epitope, and heparin sulfate binding motif of the two complete genome sequences coincided with those previously reported. Conclusions: Our research reported the genomic characterization of two novel PCV2 strains (js2021-Rt001 and js2021-Rt002) and provided the first supported evidence that PCV2d could naturally infect wild rats in China. However, whether the newly identified strains have potential for circulating in nature in vertical and horizontal transmission or inter-species jumping between rats and pigs needs further research. [ABSTRACT FROM AUTHOR]

Baicalin magnesium is a water-soluble compound isolated from the aqueous solution by Scutellaria baicalensis Georgi. Preliminary experiments have demonstrated that baicalin magnesium can exert protective effects against acute liver injury in rats induced by carbon tetrachloride or lipopolysaccharide combined with d-galactose by regulating lipid peroxidation and oxidative stress. The aim of this study was to investigate the protective effect of baicalin magnesium on non-alcoholic steatohepatitis (NASH) in rats and to elucidate the underlying mechanisms. NASH was induced through a high-fat diet (HFD) for 8 weeks, and Sprague-Dawley rats were intravenously injected with baicalin magnesium, baicalin, and magnesium sulfate for 2 weeks, respectively. Serum was obtained for biochemical analyses and the determination of oxidative stress indicators. Liver tissues were collected for use in liver index assessment, histopathological examination, inflammatory factor analysis, and protein and gene expression analysis. The results revealed that baicalin magnesium markedly improved HFD-induced lipid deposition, inflammatory response, oxidative stress, and histopathological impairments. And baicalin magnesium may exert a protective effect on NASH rats by inhibiting the NLR family pyrin domain involving the 3 (NLRP3)/caspase-1/interleukin (IL)-1β inflammatory pathway. Additionally, the effect of baicalin magnesium was remarkably superior to that of equimolar baicalin and magnesium sulfate in regard to ameliorating NASH symptoms. In conclusion, the findings suggested that baicalin magnesium may represent a potential drug for the treatment of NASH. [ABSTRACT FROM AUTHOR]

In this study, Xiushui 134Bt, a highly insect-resistant rice transgenic material with stable expression of CryIAc1 gene in rice plants and no significant changes in main agronomic traits, was obtained by means of Agrobacterium-mediated transformation method using japonica rice Xiushui 134 as receptor material. Biosecurity of the transgenic rice Xiushui 134Bt was assessed by rat feeding experiments. Wistar rats were fed a nutritionally balanced diet supplemented with 35% Genetically Modified (LGM) or 70% Genetically Modified (HGM) Xiushui 134Bt, respectively, for 90 days. Compared with the wild-type group (Xiushui 134), there were no significant differences in body weight, total food intake, food conversion rate, relative organ weight, blood routine, blood physiological or biochemical parameters, or histopathological examination between LGM and HGM Bt groups (p > 0.05). These results indicate that the transgenic rice Xiushui 134Bt is non-toxic in laboratory animals and provide guidance for the future commercial release of the transgenic rice Xiushui 134Bt in China. [ABSTRACT FROM AUTHOR]

Huangqi Jianzhong Tang (HQJZ), a famous traditional Chinese medicine formula, is widely used in the treatment of gastrointestinal diseases in China. In this study, an ultra-high-performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry was used to identify the metabolites in rat urine and feces after oral administration of HQJZ coupled with Compound Discover 3.0 software. The possible metabolic pathways were calculated and deduced based on 71 previous detected prototype compounds. As results, 88 compounds were identified in urine and feces, respectively. In urine sample, we identified 20 prototype compounds and 68 related metabolites. Meanwhile, a total of 21 prototype compounds and 67 related metabolites were identified in feces. Among them, flavonoids and saponins were the main ingredients in vivo. Further, we also speculated that HQJZ experienced oxidation, reduction, acetylation, methylation and glucuronic acid reaction in urine and feces. This study established a reliable method for the detection of prototype components and metabolites of traditional Chinese medicines, which would provide helpful information for further research into the active substances of HQJZ. [ABSTRACT FROM AUTHOR]

The mechanism of PM2.5 in the air on health is complicated, in which the gut flora may play a role. The work aimed to study the changes of intestinal microflora in PM2.5 inhaled rats, further, to analyze the expression of antibiotic resistance genes (ARGs) in intestinal flora of the rats. The PM2.5 in the air of Fujian Province of China was collected to establish the rat model of PM2.5 inhaled. The fecal samples were sequenced by metagenomic method. Intestinal flora species annotation, common function database annotation and ARGs were analyzed between PM2.5 inhaled rats and normal control rats. The results showed that the number of Firmicutes was significantly decreased while that of Bacteroides was increased in the PM2.5 inhaled rats compared with the control rats at phylum level. In addition, from genus level to species level, the composition of intestinal flora in PM2.5 inhaled group was totally different from those of control group. Especially, PM2.5 exposure can change the expression of ARGs in intestinal flora. The ARGs of rpoB2, Tet44, TetW and TetO increased significantly in the PM2.5 inhaled Wistar rats. Controlling air pollution and reducing PM2.5 emissions are crucial to maintain public health. [ABSTRACT FROM AUTHOR]

Based on the field investigation in five provincial regions of Southwest China between 2001 and 2019, the present paper reports the infestation and distribution of chigger mites on the Confucian white-bellied rat Niviventer confucianus in China for the first time. A total of 11,017 chigger mites were collected from the body surface of 911 N. confucianus rat hosts, and 10,161 of them were identified as 166 species and 16 genera in three subfamilies under two families with high species diversity (S = 166, H' = 3.19, E = 0.62). Of 911 N. confucianus rats, 341 individuals were infested with chiggers with high overall prevalence (PM = 37.43%), mean abundance (MA = 12.09 mites/rat) and mean intensity (MI = 32.31 mites/rat). On the body surface of N. confucianus, Ascoschoengastia sifanga was the most dominant chigger species followed by Walchia ewingi and Leptotrombidium rupestre. All the three dominant chigger species showed an aggregated distribution pattern among different individuals of N. confucianus. Chigger infestations on the same rat host (N. confucianus) showed some heterogeneity under different environmental conditions such as latitudes, longitudes, altitudes and landscapes. Based on Preston's lognormal model, the species abundance distribution of chiggers on N. confucianus conformed to a lognormal distribution pattern, and the predicted total species of chiggers on N. confucianus in Southwest China was estimated to be 228 species. [ABSTRACT FROM AUTHOR]

Due to the massive application of cypermethrin (CYP) for pest control in China, the adverse effects on non-target organisms have aroused great attention. However, comparative studies between its different stereoisomers remain scarce, especially for metabolism perturbations. Herein, the rats were administered α-CYP, β-CYP, and θ-CYP by gavage at doses of 8.5, 29.2, and 25.0 mg/kg/day, respectively, for 28 consecutive days. By blood examination, significant changes in liver and renal function parameters were observed in rats exposed to all three CYPs. The stereoisomeric selectivity in metabolic disturbances was assessed based on a metabolomic strategy via multivariate analysis and pathway analysis. The results demonstrated that amino acid and glycolipid metabolism were disrupted in all CYP groups. Among them, the most significant changes in the metabolic phenotype were observed in the θ-CYP group, with 56 differential metabolites enriched in 9 differential metabolic pathways. At the same time, the endogenous metabolite trimethylamine oxide (TMAO), which is closely linked to the gut microbiota, was also significantly elevated in this group. Gender differences were found in α- and θ-CYP-exposed rats, with perturbations in amino acid and glucose metabolism of greater concern in females and lipid metabolism of greater concern in males. Overall, β-CYP exhibited a lower risk of metabolic perturbations than α-CYP or θ-CYP, which helps to screen suitable agrochemical products for green agricultural development. [ABSTRACT FROM AUTHOR]

Background: While autophagy is essential for stem cells' self-renewal and differentiation, its effect on bone marrow mesenchymal stem cells (BMSCs) remains unclear. This study aimed to investigate the interaction between autophagy and osteogenic differentiation using rapamycin (RAPA), a classical autophagy agonist with osteo-regulatory effects. Methods: Rat BMSC's autophagy was analyzed after osteoinduction (0, 7, 14, and 21 d) by western blotting, immunofluorescence, and real-time quantitative polymerase chain reaction (RT-qPCR). In addition, we evaluated osteogenic differentiation using alizarin red staining, alkaline phosphatase assays, and RT-qPCR/Western blotting quantification of bone sialoprotein, type 1 collagen, alkaline phosphatase, osteopontin, and Runt-related transcription factor 2 mRNA and protein levels. Results: The BMSC's basal autophagy level gradually decreased during osteogenic differentiation with a decrease in BECN1 level and the lipidated (LC3-II) to unlipidated (LC3-I) microtubule-associated protein 1 light chain 3 ratio and an increase in the expression of selective autophagic target p62. In contrast, it increased with increasing RAPA concentration. Furthermore, while 2 nM RAPA promoted BMSC osteogenic differentiation on days 7 and 14, 5 nM RAPA inhibited osteogenesis on days 14 and 21. Inhibition of autophagy by the inhibitor 3-methyladenine could impair RAPA's osteogenesis-enhancing effect on BMSCs. Conclusions: The BMSC's basal autophagy level decreased over time during osteogenic differentiation. However, an appropriate RAPA concentration promoted BMSC osteogenic differentiation via autophagy activation. [ABSTRACT FROM AUTHOR]