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1.
PLoS One ; 19(4): e0301702, 2024.
Article in English | MEDLINE | ID: mdl-38573944

ABSTRACT

BACKGROUND: ChatGPT is a large language model designed to generate responses based on a contextual understanding of user queries and requests. This study utilised the entrance examination for the Master of Clinical Medicine in Traditional Chinese Medicine to assesses the reliability and practicality of ChatGPT within the domain of medical education. METHODS: We selected 330 single and multiple-choice questions from the 2021 and 2022 Chinese Master of Clinical Medicine comprehensive examinations, which did not include any images or tables. To ensure the test's accuracy and authenticity, we preserved the original format of the query and alternative test texts, without any modifications or explanations. RESULTS: Both ChatGPT3.5 and GPT-4 attained average scores surpassing the admission threshold. Noteworthy is that ChatGPT achieved the highest score in the Medical Humanities section, boasting a correct rate of 93.75%. However, it is worth noting that ChatGPT3.5 exhibited the lowest accuracy percentage of 37.5% in the Pathology division, while GPT-4 also displayed a relatively lower correctness percentage of 60.23% in the Biochemistry section. An analysis of sub-questions revealed that ChatGPT demonstrates superior performance in handling single-choice questions but performs poorly in multiple-choice questions. CONCLUSION: ChatGPT exhibits a degree of medical knowledge and the capacity to aid in diagnosing and treating diseases. Nevertheless, enhancements are warranted to address its accuracy and reliability limitations. Imperatively, rigorous evaluation and oversight must accompany its utilization, accompanied by proactive measures to surmount prevailing constraints.


Subject(s)
Artificial Intelligence , Clinical Medicine , Educational Measurement , Language , Reproducibility of Results
2.
Heliyon ; 10(4): e25616, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38375275

ABSTRACT

Pigs are natural host to various zoonotic pathogens including viruses. In this study, we analyzed the viral communities in the feces of 89 piglets with diarrhea under one month old which were collected from six farms in Jiangsu Province of the Eastern China, using the unbiased virus metagenomic method. A total of 89 libraries were constructed, and 46937894 unique sequence reads were generated by Illumina sequencing. Overall, the family Picornaviridae accounted for the majority of the total reads of putative mammalian viruses. Ten novel virus genomes from different family members were discovered, including Parvoviridae (n = 2), Picobirnaviridae (n = 4) and CRESS DNA viruses (n = 4). A large number of phages were identified, which mainly belonged to the order Caudovirales and the family Microviridae. Moreover, some identified viruses were closely related to viruses found in non-porcine hosts, highlighting the potential for cross-species virus dissemination. This study increased our understanding of the fecal virus communities of diarrhea piglets and provided valuable information for virus monitoring and preventing.

3.
Prog Orthod ; 25(1): 2, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38185724

ABSTRACT

BACKGROUND: Orthodontic tooth movement (OTM) in a region containing alveolar bone defects with insufficient height and width is hard to achieve. Bovine bone mineral (Bio-Oss) is available to restore the alveolar defect; however, whether the region augmented with a bovine bone mineral graft (BG) is feasible for OTM, and the mechanisms by which macrophages remodel the BG material, is uncertain under the mechanical force induced by OTM. MATERIAL AND METHODS: Rats were divided into three groups: OTM (O), OTM + BG material (O + B), and Control (C). First molars were extracted to create bone defects in the O and O + B groups with bovine bone mineral grafting in the latter. Second molars received OTM towards the bone defects in both groups. After 28 days, maxillae were analyzed using microfocus-computed tomography (µCT) and scanning-electron-microscopy (SEM); and macrophages (M1/M2) were stained using immunofluorescence. THP-1 cell-induced macrophages were cultured under mechanical force (F), BG material (B), or both (F + B). Phagocytosis-related signaling molecules (cAMP/PKA/RAC1) were analyzed, and conditioned media was analyzed for MMP-9 and cytokines (IL-1ß, IL-4). RESULTS: Our study demonstrated that alveolar defects grafted with BG materials are feasible for OTM, with significantly increased OTM distance, bone volume, and trabecular thickness in this region. SEM observation revealed that the grafts served as a scaffold for cells to migrate and remodel the BG materials in the defect during OTM. Moreover, the population of M2 macrophages increased markedly both in vivo and in cell culture, with enhanced phagocytosis via the cAMP/PKA/RAC1 pathway in response to mechanical force in combination with BG particles. By contrast, M1 macrophage populations were decreased under the same circumstances. In addition, M2 macrophage polarization was also indicated by elevated IL-4 levels, reduced IL-1ß levels, and less active MMP-9 in cell culture. CONCLUSION: This study explored the mechanisms of mechanical force-induced alveolar bone remodeling with bovine bone mineral grafts during OTM. The results might provide molecular insights into the related clinical problems of whether we can move teeth into the grafted materials; and how these materials become biologically remodeled and degraded under mechanical force.


Subject(s)
Interleukin-4 , Matrix Metalloproteinase 9 , Animals , Cattle , Rats , Tooth Movement Techniques , Minerals
4.
Neurosci Bull ; 40(4): 483-499, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37979054

ABSTRACT

Chronic cerebral hypoperfusion is one of the pathophysiological mechanisms contributing to cognitive decline by causing white matter injury. Microglia phagocytosing myelin debris in a timely manner can promote remyelination and contribute to the repair of white matter. However, milk fat globule-epidermal growth factor-factor 8 (MFG-E8), a microglial phagocytosis-related protein, has not been well studied in hypoperfusion-related cognitive dysfunction. We found that the expression of MFG-E8 was significantly decreased in the brain of mice after bilateral carotid artery stenosis (BCAS). MFG-E8 knockout mice demonstrated more severe BCAS-induced cognitive impairments in the behavioral tests. In addition, we discovered that the deletion of MFG-E8 aggravated white matter damage and the destruction of myelin microstructure through fluorescent staining and electron microscopy. Meanwhile, MFG-E8 overexpression by AAV improved white matter injury and increased the number of mature oligodendrocytes after BCAS. Moreover, in vitro and in vivo experiments showed that MFG-E8 could enhance the phagocytic function of microglia via the αVß3/αVß5/Rac1 pathway and IGF-1 production to promote the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes. Interestingly, we found that MFG-E8 was mainly derived from astrocytes, not microglia. Our findings suggest that MFG-E8 is a potential therapeutic target for cognitive impairments following cerebral hypoperfusion.


Subject(s)
Brain Ischemia , Cognitive Dysfunction , Remyelination , Mice , Animals , Myelin Sheath , Phagocytosis/physiology , Microglia/metabolism , Cognitive Dysfunction/etiology , Cognitive Dysfunction/metabolism , Brain Ischemia/complications , Brain Ischemia/metabolism , Mice, Knockout , Mice, Inbred C57BL
5.
Chin J Dent Res ; 26(3): 153-162, 2023 Sep 21.
Article in English | MEDLINE | ID: mdl-37732681

ABSTRACT

OBJECTIVE: To explore the high-efficiency and low-risk prevention and treatment strategies for stem cells from human exfoliated deciduous teeth (SHED) for high-altitude cerebral oedema. METHODS: A low-pressure and low-oxygen tank mimicking high-altitude conditions was used to establish the high-altitude cerebral oedema animal model. The preventive effects of SHED for cerebral oedema were then evaluated by haematoxylin and eosin (H&E) and histological staining. In vitro, SHED was co-cultured with BV-2 to analyse the effects of SHED by western blot and immunofluorescence staining. RESULTS: SHED can prevent and treat cerebral oedema in a high altitude rat animal model. Mechanistically, SHED treatment can protect brain cells from apoptosis induced by high altitude condition. Moreover, SHED treatment can inhibit M1-type polarisation and promote M2-type polarisation of microglia cells via the suppression of hypoxia inducible factor (HIF)- 1α-mediated extracellular signal-regulated kinase (ERK) signalling activated in high altitude condition. CONCLUSION: SHED treatment can relieve high-altitude cerebral oedema via inhibiting HIF- 1α-mediated ERK signalling, which indicates that SHED is a promising alternative strategy to prevent and treat high-altitude cerebral oedema.


Subject(s)
Altitude Sickness , Brain Edema , Humans , Animals , Rats , Brain Edema/etiology , Brain Edema/therapy , Microglia , Altitude , Stem Cells , Extracellular Signal-Regulated MAP Kinases , Tooth, Deciduous
6.
ACS Appl Mater Interfaces ; 15(38): 44742-44751, 2023 Sep 27.
Article in English | MEDLINE | ID: mdl-37721982

ABSTRACT

Exploring new ways to reconstruct the structure and function of inappropriate organic fluorophores for improving amyloid-ß (Aß) fluorescent imaging performance is desired for precise detection and early diagnosis of Alzheimer's disease (AD). With stilbazolium dyes as examples, here, we present a multipronged approach to comprehensively improved the Aß fluorescent imaging performance through a flexible bivalent method, where a flexible carbon chain was introduced to link two monomers to form a homodimer. Our results reveal a mechanism wherein the flexible linker creates a well-defined probe with specific orientations and distinct photophysical properties. Applying this approach in combination with theoretical simulation, the homodimers exhibited a comprehensive improvement of the Aß fluorescent imaging performance of the dye monomers, including better photostability and higher signal-to-noise (S/N) ratio, higher "off-on" near-infrared fluorescence (NIRF) response sensitivity, higher specificity and affinity to Aß deposits, and more reasonable lipophilicity for blood-brain barrier (BBB) penetrability. The results demonstrate that flexible homodimers offer a multipronged approach to obtaining high-performance NIRF imaging reagents for the detection of Aß deposits both in vitro and in vivo.


Subject(s)
Alzheimer Disease , Fluorescent Dyes , Humans , Amyloid beta-Peptides , Alzheimer Disease/diagnostic imaging , Blood-Brain Barrier , Carbon
7.
Heliyon ; 9(6): e17222, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37389044

ABSTRACT

Viral diseases caused by new outbreaks of viral infections pose a serious threat to human health. Wild brown rats (Rattus norvegicus), considered one of the world's largest and most widely distributed rodents, are host to various zoonotic pathogens. To further understand the composition of the virus community in wild brown rats and explore new types of potentially pathogenic viruses, viral metagenomics was conducted to investigate blood, feces, and various tissues of wild brown rats captured from Zhenjiang, China. Results indicated that the composition of the virus community in different samples showed significant differences. In blood and tissue samples, members of the Parvoviridae and Anelloviridae form the main body of the virus community. Picornaviridae, Picobirnaviridae, and Astroviridae made up a large proportion of fecal samples. Several novel genome sequences from members of different families, including Anelloviridae, Parvoviridae, and CRESS DNA viruses, were detected in both blood and other samples, suggesting that they have the potential to spread across organs to cause viremia. These viruses included not only strains closely related to human viruses, but also a potential recombinant virus. Multiple dual-segment picornaviruses were obtained from fecal samples, as well as virus sequences from the Astroviridae and Picornaviridae. Phylogenetic analysis showed that these viruses belonged to different genera, with multiple viruses clustered with other animal viruses. Whether they have pathogenicity and the ability to spread across species needs further study.

8.
Microbiol Spectr ; 11(3): e0472722, 2023 06 15.
Article in English | MEDLINE | ID: mdl-37166308

ABSTRACT

During a 2020 routine epidemiological investigation of carbapenem-resistant Enterobacterales at a local food market in Guangzhou, China, two Escherichia coli ST410 isolates coproducing NDM-5 and OXA-181 were obtained from environmental samples. Antimicrobial susceptibility testing, whole-genome sequencing, and conjugation assays were applied to identify their resistance phenotypes, phylogenetic relatedness, and genetic characteristics. Phylogenetic analysis showed that the two isolates were clonally related with only one core-genome single-nucleotide polymorphism (SNP) difference and clustered into a branch with 87 E. coli ST410 isolates deposited in GenBank. These 89 ST410 isolates were closely related (≤51 SNPs), and most were from humans in Southeast Asian countries (n = 47). A Vietnamese clinical isolate collected in 2017 showed the strongest epidemiological link (seven SNPs) to the two ST410 isolates detected in this study. Complete-genome analysis revealed that the carbapenem resistance determinants blaNDM-5 and blaOXA-181 were located on an IncF1:A1:B49-IncQ1 plasmid and IncX3 plasmid, respectively. Conjugation experiments confirmed that the IncX3 plasmid was self-transmissible while the IncF1:A1:B49-IncQ1 plasmid was nonconjugative. BLASTn analysis indicated that the two plasmids showed high similarity to other blaNDM-5-bearing IncF1:A1:B49-IncQ1 and blaOXA-181-bearing IncX3 plasmids from other countries. Altogether, the high similarity of the core genomes and plasmids between the ST410 isolates found in this study and those human source isolates from foreign countries suggested the clonal spread of E. coli ST410 strains and horizontal transmission of blaOXA-181-bearing IncX3 plasmids across Southeast Asian countries. Stringent sanitary management of food markets is important to prevent the dissemination of high-risk clones to the public. IMPORTANCE This is the first report of an Escherichia coli ST410 clone that coproduces NDM-5 and OXA-181 in China. The high similarity of the core genomes and plasmids between the ST410 isolates characterized in this study and human source isolates from foreign countries strongly suggests that this ST410 lineage is an international high-risk clone, highlighting the need for continuous global surveillance of ST410 clones.


Subject(s)
Escherichia coli Infections , Escherichia coli , Humans , Escherichia coli Infections/epidemiology , Phylogeny , beta-Lactamases/genetics , Carbapenems/pharmacology , Plasmids/genetics , China/epidemiology , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology
9.
Cereb Cortex ; 33(5): 1693-1707, 2023 02 20.
Article in English | MEDLINE | ID: mdl-35512682

ABSTRACT

Establishing neuronal circuits requires interactions between pre- and postsynaptic neurons. While presynaptic neurons were shown to play instructive roles for the postsynaptic neurons, how postsynaptic neurons provide feedback to regulate the presynaptic neuronal development remains elusive. To elucidate the mechanisms for circuit formation, we study the development of barrel cortex (the primary sensory cortex, S1), whose development is instructed by presynaptic thalamocortical axons (TCAs). In the first postnatal weeks, TCA terminals arborize in layer (L) 4 to fill in the barrel center, but it is unclear how TCA development is regulated. Here, we reported that the deletion of Lhx2 specifically in the cortical neurons in the conditional knockout (cKO) leads to TCA arborization defects, which is accompanied with deficits in sensory-evoked and spontaneous cortical activities and impaired lesion-induced plasticity following early whisker follicle ablation. Reintroducing Lhx2 back in L4 neurons in cKO ameliorated TCA arborization and plasticity defects. By manipulating L4 neuronal activity, we further demonstrated that Lhx2 induces TCA arborization via an activity-dependent mechanism. Additionally, we identified the extracellular signaling protein Sema7a as an activity-dependent downstream target of Lhx2 in regulating TCA branching. Thus, we discovered a bottom-up feedback mechanism for the L4 neurons to regulate TCA development.


Subject(s)
Neurons , Thalamus , Feedback , Thalamus/physiology , Neurons/physiology , Axons/physiology , Signal Transduction , Somatosensory Cortex/physiology
10.
Front Cell Neurosci ; 16: 981190, 2022.
Article in English | MEDLINE | ID: mdl-36187288

ABSTRACT

Trigeminal neuralgia (TN) is a peripheral nerve disorder often accompanied by abnormalities in mood. The lateral habenula (LHb) plays important roles in the modulation of pain and emotion. In the present study, we investigated the involvement of the LHb in the mechanisms underlying allodynia and anxiety induced by partial transection of the infraorbital nerve (pT-ION) in mice. Our results indicated that pT-ION induced persistent orofacial allodynia and anxiety-like behaviors, which were correlated with increased phosphorylation of N-Methyl D-aspartate receptor (NMDAR) subtype 2B (p-NR2B) and Ca2+/calmodulin-dependent protein kinase II (p-CaMKII) in LHb neurons. Bilateral inhibition of NMDARs and CaMKII in the LHb attenuated the allodynia and anxiety-like behavior induced by pT-ION. Furthermore, bilateral activation of NMDARs in the LHb increased the expression of p-NR2B and p-CaMKII and induced orofacial allodynia and anxiety-like behaviors in naive mice. Adeno-associated virus (AAV)-mediated expression of hM3D(Gq) in CaMKII+ neurons of the bilateral LHb, followed by clozapine-N-oxide (CNO) administration, also triggered orofacial allodynia and anxiety-like behaviors in naïve mice with successful virus infection in LHb neurons (verified based on immunofluorescence). In conclusion, these findings suggest that activation of NMDA/CaMKII signaling in the LHb contributes to the occurrence and development of TN and related anxiety-like behaviors. Therefore, suppressing the activity of CaMKII+ neurons in the bilateral LHb by targeting NMDA/CaMKII may represent a novel strategy for treating pain and anxiety associated with TN.

11.
Front Vet Sci ; 9: 878441, 2022.
Article in English | MEDLINE | ID: mdl-35782540

ABSTRACT

Since 2014, a goose-origin astroviruses disease, which is characterized by urate precipitation in viscera, has rapidly spread to major commercial goose provinces leading to huge economic losses in the poultry industry of China. In March 2020, a goose farm locates in Shanghai, China, where there was no goose astroviruses (GAstVs) infection reported before, experienced an outbreak of gout disease in geese. The etiological investigation was carried out by virus metagenomics and bacterial culture and two GAstVs strains, designated as CHSH01 and CHSH02, were determined. Their complete genomes were measured to 7,154 and 7,330 nt in length, excludingthe poly(A) tail, respectively, and had different genomic features and classifications. CHSH01 shared a very low sequence identity with other strains in terms of not only the complete genome but also different ORFs. Phylogenetic analysis showed CHSH02 belonged to GAstV-2, which was the predominant species in the geese with gout in China according to the previous study. Meanwhile, CHSH01 strain displayed low identity with other AstVs, and phylogenetic and recombination analysis suggested that CHSH01 belonging to a novel type was a recombinant strain, one parent strain of which was an AstV determined from a bar-headed goose (a kind of migrant bird). Moreover, the primary epidemiological investigation showed that the two strains were prevalent in the same goose farm and co-infection occurred. These findings arise the potential cross-species transmission of CHSH01 between domestic and wild fowl.

12.
Exp Mol Pathol ; : 104806, 2022 Jul 04.
Article in English | MEDLINE | ID: mdl-35798064

ABSTRACT

SHARPIN (Shank-associated RH domain interacting protein) plays an important role in tumorigenesis. However, its role in ovarian cancer remains largely unknown. To investigate this issue, we systematically analyzed the amplification and expression of the SHARPIN in the TCGA database. From the database, we found that SHARPIN was amplified in ovarian cancer compared to normal ovarian tissue, and the mRNA level of SHARPIN was significantly elevated in ovarian cancer compared to non-tumorigenic ovarian tissue. In addition, we observed similar results from ovarian cancer cell lines and clinical samples from ovarian cancer patients, which indicated that increased SHARPIN expression is associated with tumorigenesis in ovarian cancer. SHARPIN knockdown inhibited the migration and invasion of ovarian cancer cells, also inhibited cell cycle and promoted apoptosis, thereby suppressing cell proliferation. RNA-seq results showed that SHARPIN significantly increased the expression of P53 and P21 and decreased the expression of Cyclin D1 and c-Myc, all of which are involved in the regulation of cell proliferation. Subsequent mechanistic exploration revealed that SHARPIN knockdown increased the expression of caspases 3 and 9, leading to apoptosis of ovarian cancer cells. We also found that high expression of SHARPIN was associated with poor prognosis of ovarian cancer patients. Collectively, we demonstrated a positive correlation between SHARPIN and ovarian cancer progression and provide a basis for combined targeted therapy strategies for future ovarian cancer treatment.

13.
Front Immunol ; 13: 860225, 2022.
Article in English | MEDLINE | ID: mdl-35634294

ABSTRACT

Liver cirrhosis represents a type of end-stage liver disease with few effective therapies, which was characterized by damaged functional liver tissue due to long-term inflammation. Gasdermin D (GSDMD)-executed programmed necrosis is reported to be involved in inflammation. However, the role of GSDMD in liver cirrhosis remains unclear. In this study, we used a CCl4-induced cirrhosis model and found stem cells from human exfoliated deciduous teeth (SHED) infusion showed profound therapeutic effects for liver cirrhosis. Mechanistically, NLRP3 inflammasome-activated GSDMD and its pyroptosis were upregulated in liver cirrhosis, while SHED infusion could suppress the expression of GSDMD and Caspase-1, resulting in reduced hepatocyte pyroptosis and inflammatory cytokine IL-1ß release. Consistently, SHED could inhibit the elevated expression of NLRP3, GSDMD and Caspase-1 induced by CCl4 treatment in vitro co-culture system, which was mediated by decreasing reactive oxygen species (ROS) generation. Moreover, the pyroptosis inhibitor disulfiram showed similar therapeutic effects for liver cirrhosis as SHED. In conclusion, SHED alleviates CCl4-induced liver cirrhosis via inhibition of hepatocytes pyroptosis. Our findings could provide a potential treatment strategy and novel target for liver cirrhosis.


Subject(s)
NLR Family, Pyrin Domain-Containing 3 Protein , Pyroptosis , Caspase 1/metabolism , Hepatocytes/metabolism , Humans , Inflammation , Intracellular Signaling Peptides and Proteins/metabolism , Liver Cirrhosis/chemically induced , Liver Cirrhosis/therapy , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Phosphate-Binding Proteins/metabolism , Stem Cells/metabolism , Tooth, Deciduous
14.
J Therm Biol ; 105: 103220, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35393054

ABSTRACT

Heat stress causes economic loss of livestock industry in tropical areas. Exploring genetic markers for selection of thermotolerance will benefit chicken production. Oxidative stress and fluid-salt balance are tightly associated with thermotolerance and productivity in domestic animals. The study aimed to identify single-nucleotide polymorphisms (SNPs) in genes related to oxidative stress and ion-channel regulation and their associations with semen quality and hormonal responses. In total, 28 SNPs within 11 candidate genes were identified to associate with hormonal changes and semen quality in both broiler- and layer-type Taiwan country chickens (TCCs) after exposure to acute heat stress at 38 °C for 4 h. Acute heat stress significantly affected plasma levels of triiodothyronine and corticosterone and reduced sperm motility, viability, and concentrations in both strains at Day 1 after exposure. In the B-strain TCCs, five SNPs within NDUFA8 and DAB2IP had significant effects on plasma adrenaline and corticosterone levels, and six SNPs within TRPC1, SLC9A9, and TRPC7 markedly affected plasma corticosterone and triiodothyronine levels. In the L2 strain, 15 SNPs within PSMA2, TPK1, MTF1, and CUL1 exerted effects on plasma corticosterone and triiodothyronine levels. Five SNPs within CUL3, TRPC1, and SLC9A9 in the B strain and two SNPs within MTF1 in the L2 strain were associated with sperm concentrations at Day 1 after exposure to heat stress. In conclusion, acute heat stress impaired semen quality and altered plasma corticosterone and triiodothyronine levels in TCCs. Some SNPs involved in oxidative stress and ion-channel regulation were identified to associate with the hormonal and semen alterations. These SNPs in conjunction with differential hormonal responses and semen quality serve as genetic markers for thermotolerance selection in sire lines of chickens.


Subject(s)
Chickens , Heat Stress Disorders , Animals , Male , Chickens/genetics , Corticosterone , Genetic Markers , Heat Stress Disorders/veterinary , Oxidative Stress , Polymorphism, Single Nucleotide , Semen Analysis , Sperm Motility , Triiodothyronine
15.
J Ethnopharmacol ; 289: 115057, 2022 May 10.
Article in English | MEDLINE | ID: mdl-35121050

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Hehuan Yin decoction (HHY), first recorded in the Jingyue Quanshu (published in 1624 A.D.), is composed of Albizia julibrissin Durazz. and Ampelopsis japonica (Thunb.) Makino. AIM OF THE STUDY: This study aimed to investigate the mechanism of action of HHY in treating polycystic ovary syndrome with insulin resistance (PCOS-IR). MATERIALS AND METHODS: Network pharmacology and molecular docking were used to predict active compounds, potential targets, and pathways for PCOS-IR treatment using HHY. Female Sprague-Dawley rats were administered letrozole (1 mg/kg) with a high-fat diet to establish a PCOS-IR model. Thereafter, symptoms, ovarian pathology, serum insulin resistance, and sex hormone levels were determined. Western blotting was used to determine the levels of PI3Kp85α, AKT, phospho (p)-AKT, and GSK3ß in the ovaries of rats. RESULTS: Network pharmacology revealed 58 components in HHY and 182 potential targets that were shared between HHY and PCOS-IR. HHY could potentially treat PCOS-IR via the insulin resistance, PI3K/AKT, HIF-1, and steroid hormone biosynthesis pathways. Molecular docking revealed that PI3K, AKT1, GSK3ß, IRS1, and EGFR had high affinities to HHY compounds. In the PCOS-IR rats, HHY significantly normalised the symptoms and ovarian pathology, increased follicle-stimulating hormone (FSH) and oestradiol levels in the serum, and decreased the levels of fasting plasma glucose and fasting insulin, as well as the insulin resistance index. HHY also decreased the luteinising hormone (LH) and testosterone levels and the LH/FSH ratio in the PCOS-IR rats and increased the levels of PI3K, p-AKT, and GSK3ß in ovary tissue, which indicated the activation of the PI3K/AKT pathway. CONCLUSIONS: HHY can improve PCOS-IR symptoms via multiple pharmacological pathways and may be a potential alternative therapy for the treatment of PCOS-IR.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Insulin Resistance , Polycystic Ovary Syndrome/drug therapy , Animals , Diet, High-Fat , Disease Models, Animal , Female , Letrozole , Molecular Docking Simulation , Network Pharmacology , Phosphatidylinositol 3-Kinase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Sprague-Dawley
16.
Hum Cell ; 35(3): 896-908, 2022 May.
Article in English | MEDLINE | ID: mdl-35174471

ABSTRACT

Ovarian cancer is one of the most lethal gynecologic malignancies worldwide, with the 5-year survival is less than 50%. Although some clinical achievements have been achieved, the overall survival rate has remained unchanged over the past 20 years. Therefore, it is necessary and urgent to develop the potential modifiers and therapeutic approach to improve the overall survival rate in ovarian cancer patients. RBCK1 is an RING protein E3 ubiquitin ligase, which was revealed to involve in the progression of several cancers through its ubiquitination function. In this research, we report that RBCK1 expression is significantly elevated in human ovarian cancer and strongly associated with poor patients' prognosis. RBCK1 deficiency induces cell apoptosis and inhibits cell proliferation and migration in ovarian cancer cells. In terms of molecular mechanism, we report that RBCK1 interacts with PTEN and promotes PTEN degradation in K48-linked ubiquitination. Our study suggests a new and interesting regulatory mechanism that RBCK1 facilitates PTEN degradation, which could be a new potential therapeutic target for ovarian cancer treatment.


Subject(s)
Ovarian Neoplasms , Ubiquitin-Protein Ligases , Cell Line, Tumor , Cell Proliferation/genetics , Female , Humans , Ovarian Neoplasms/genetics , Ovarian Neoplasms/therapy , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism , Transcription Factors/genetics , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Ubiquitination
17.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-976122

ABSTRACT

@#Objective - ( ) To analyze the current situation of work related musculoskeletal disorders WMSDs in neck and low , Methods back of acupuncturists and to explore its influencing factors. A total of 272 acupuncturists from 21 hospitals above grade B level in Guangdong Province were selected as study subjects using convenient sampling method. The revised Chinese , version of Musculoskeletal Disorders Questionnaire was used to investigate the prevalence of WMSDs in the past one year and Results the influencing factors of WMSDs in the high incidence areas such as neck and low back were analyzed. The annual ( ), ( ) prevalence of WMSDs among acupuncturists was 94.9%. The prevalence of WMSDs in the neck 81.6% low back 81.6% ( ) , and shoulder 63.2% was the highest and the prevalence of WMSDs in both the neck and low back was 73.5%. The prevalence - - ( vs ,P ) of multi site WMSDs was higher than that of single site WMSDs 86.0% 8.8% <0.01 . Multivariate logistic regression , - , , analysis showed that acupuncturists who were female long time sitting work repeated operations within one minute and work ( P ) changing every day were common risk factors for neck or low back WMSDs or both neck and low back all <0.05 . Keeping the , , same posture for a long time driving to work and personnel shortage were risk factors for low back WMSDs in acupuncturists ( P ) (P )Conclusion all <0.05 . Uncomfortable working posture was a risk factor for WMSDs in both neck and low back <0.05 . - , - Acupuncturists are the high risk population of WMSDs and the neck and low back are the high risk sites of WMSDs. The influencing factors of WMSDs in acupuncturists include individual factors and occupational factors such as poor ergonomics and work organization.

18.
Sci Adv ; 7(27)2021 07.
Article in English | MEDLINE | ID: mdl-34215582

ABSTRACT

Development of cortical regions with precise, sharp, and regular boundaries is essential for physiological function. However, little is known of the mechanisms ensuring these features. Here, we show that determination of the boundary between neocortex and medial entorhinal cortex (MEC), two abutting cortical regions generated from the same progenitor lineage, relies on COUP-TFI (chicken ovalbumin upstream promoter-transcription factor I), a patterning transcription factor with graded expression in cortical progenitors. In contrast with the classical paradigm, we found that increased COUP-TFI expression expands MEC, creating protrusions and disconnected ectopic tissue. We further developed a mathematical model that predicts that neuronal specification and differential cell affinity contribute to the emergence of an instability region and boundary sharpness. Correspondingly, we demonstrated that high expression of COUP-TFI induces MEC cell fate and protocadherin 19 expression. Thus, we conclude that a sharp boundary requires a subtle interplay between patterning transcription factors and differential cell affinity.


Subject(s)
Neocortex , COUP Transcription Factor I/metabolism , Cell Adhesion , Entorhinal Cortex , Neocortex/metabolism , Transcription Factors/metabolism
19.
Zhongguo Zhong Yao Za Zhi ; 46(11): 2857-2864, 2021 Jun.
Article in Chinese | MEDLINE | ID: mdl-34296586

ABSTRACT

The liver and kidney fibrosis model was established by thioacetamide(TAA) and unilateral ureteral obstruction(UUO) in SD rats. The rats were randomly divided into three groups: model group, low and high-dose groups of C21 steroidal glycosides of Cynanchum auriculatum. Another blank control group was set. Four weeks later, serum was taken to detect the biochemical indexes of liver and kidney function. Urine protein and urine creatinine were detected by kits. Liver and kidney tissue samples were stained with HE and Masson staining, and hydroxyproline content was detected. Western blot was used to detect expressions of fibrotic proteins, inflammatory factors and TLR4 signaling pathways, so as to observe the preventive and therapeutic effects of C21 steroidal glycosides from C. auriculatum on hepatic and renal fibrosis and explore its molecular mechanism. Four weeks later, serum biochemical results showed that liver and kidney functions were seriously damaged, and pathological sections showed that inflammatory cell infiltration, decrease of parenchymal cells, and increase of interstitial fibrosis in liver and kidney tissues. The results showed that low and high doses(150, 300 mg·kg~(-1)) of C21 steroidal glycosides could significantly reduce the collagen deposition and the pathological changes of liver and kidney fibrosis compared with the model group. At the same time, we found that the expression levels of TLR4 and MyD88 signaling pathway proteins were significantly increased in the liver and kidney tissues of the model group, and a large number of NF-κB signaling pathway proteins migrated into the nucleus. On the contrary, the expression levels of TLR4, MyD88 signaling pathway proteins and the nuclear migration of NF-κB were significantly inhibited in the low and high dose groups of C21 steroidal glycosides from C. auriculatum. Therefore, it was speculated that the mechanism of C21 steroidal glycoside for preventive and therapeutic effect on hepatic and renal fibrosis was related to inhibit TLR4/MYD88/NF-κB inflammatory pathway, thus preventing hepatic and renal fibrosis.


Subject(s)
Cynanchum , Animals , Fibrosis , Glycosides , Kidney/pathology , Liver , NF-kappa B/genetics , Rats , Rats, Sprague-Dawley , Toll-Like Receptor 4/genetics
20.
World J Clin Cases ; 9(19): 5252-5258, 2021 Jul 06.
Article in English | MEDLINE | ID: mdl-34307575

ABSTRACT

BACKGROUND: Indwelling colon is characterized by an excluded segment of the colon after surgical diversion of the fecal stream with colostomy so that contents are unable to pass through this part of the colon. We report a rare case of purulent colonic necrosis that occurred 7 years after surgical colonic exclusion. CASE SUMMARY: A 73-year-old male had undergone extended radical resection for rectosigmoid cancer. The invaded ileocecal area and sigmoid colon were removed during the procedure, and the ileum was anastomosed side-to-side with the rectum. The excluded ascending, transverse, and descending colon were sealed at both ends and left in the abdomen. After 7 years, the patient developed persistent abdominal pain and distension. Work-up indicated intestinal obstruction. The patient underwent ultrasound-guided catheter drainage of the descending colon and a large amount of viscous liquid was drained, but the symptoms persisted; therefore, surgery was planned. Intraoperatively, extensive adhesions were found in the abdominal cavity, and the small intestine and the indwelling colon were widely dilated. The dilated colon was 56 cm long, 5 cm wide (diameter), and contained about 1500 mL of viscous liquid. The indwelling colon was surgically removed and its histopathological examination revealed colonic congestion and necrosis with hyperplasia of granulation tissue. The bacterial culture of the secretions was negative. The patient recovered after the operation. CONCLUSION: Although colonic exclusion is routinely performed, this report aimed to increase awareness regarding the possible long-term complications of indwelling colon.

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