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1.
J Vis Exp ; (205)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38557978

RESUMO

Peyronie's Disease (PD) is clinically characterized by the development of localized fibrous plaques, primarily on the tunica albuginea, especially on the dorsal area of the penis. These plaques are the hallmark feature of this condition, resulting in penile curvature, deformity, and painful erections for affected individuals. Although various nonsurgical treatment options exist, their overall effectiveness is limited. As a result, surgical intervention has become the ultimate choice for patients with severe penile curvature deformities and associated erectile dysfunction. Our research team has successfully employed a combined approach involving microscopic electric rotary grinding of the fibrous plaques and the use of tunica vaginalis or bovine pericardium as graft materials for the repairing of the defects of tunica albuginea in the treatment of PD. This approach has consistently yielded highly satisfactory results regarding the restoration of penile shape, with excellent cosmetic results and significantly improved sexual satisfaction. This protocol aims to present a comprehensive surgical management strategy utilizing electric rotary grinding of the plaques and repairing the defects of tunica albuginea by using the tunica vaginalis, which represents an optimal surgical strategy for treating PD.


Assuntos
Disfunção Erétil , Induração Peniana , Placa Aterosclerótica , Masculino , Humanos , Animais , Bovinos , Induração Peniana/cirurgia , Pênis , Disfunção Erétil/etiologia , Disfunção Erétil/cirurgia , Fibrose , Placa Amiloide
2.
Bioorg Chem ; 144: 107175, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38335757

RESUMO

Eight undescribed (1-8) and 46 known compounds (9-54) were isolated from the deep-sea-derived Aspergillus sp. MCCC 3A00392. Compounds 1-3 were three novel oxoindolo diterpenoids, 4-6 were three bisabolane sesquiterpenoids, while 7 and 8 were two monocyclic cyclopropanes. Their structures were established by exhaustive analyses of the HRESIMS, NMR, and theoretical calculations of the NMR data and ECD spectra. Compounds 10, 33, 38, and 39 were able to inhibit tumor necrosis factor (TNF)-induced necroptosis in murine L929 cell lines. Functional experiments verified that compounds 10 and 39 inhibited necroptosis by downregulating the phosphorylation of RIPK3 and MLKL. Moreover, compound 39 also reduced the phosphorylation of RIPK1. Compounds 10, 33, and 34 displayed potent inhibitory activities against RSL-3 induced ferroptosis with the EC50 value of 3.0 µM, 0.4 µM, and 0.1 µM, respectively. Compound 10 inhibited ferroptosis by the downregulation of HMOX1, while compounds 33 and 34 inhibited ferroptosis through regulation of NRF2/SLC7A11/GCLM axis. However, these compounds only showed weak effect in either the necroptosis or ferroptosis relative mouse disease models. Further studies of pharmacokinetics and pharmacodynamics might improve their in vivo bioactivities.


Assuntos
Ferroptose , Sesquiterpenos , Camundongos , Animais , Necroptose , Aspergillus/química , Sesquiterpenos/química , Sesquiterpenos Monocíclicos
3.
Microbiome ; 12(1): 35, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38378577

RESUMO

BACKGROUND: Haemaphysalis longicornis is drawing attentions for its geographic invasion, extending population, and emerging disease threat. However, there are still substantial gaps in our knowledge of viral composition in relation to genetic diversity of H. longicornis and ecological factors, which are important for us to understand interactions between virus and vector, as well as between vector and ecological elements. RESULTS: We conducted the meta-transcriptomic sequencing of 136 pools of H. longicornis and identified 508 RNA viruses of 48 viral species, 22 of which have never been reported. Phylogenetic analysis of mitochondrion sequences divided the ticks into two genetic clades, each of which was geographically clustered and significantly associated with ecological factors, including altitude, precipitation, and normalized difference vegetation index. The two clades showed significant difference in virome diversity and shared about one fifth number of viral species that might have evolved to "generalists." Notably, Bandavirus dabieense, the pathogen of severe fever with thrombocytopenia syndrome was only detected in ticks of clade 1, and half number of clade 2-specific viruses were aquatic-animal-associated. CONCLUSIONS: These findings highlight that the virome diversity is shaped by internal genetic evolution and external ecological landscape of H. longicornis and provide the new foundation for promoting the studies on virus-vector-ecology interaction and eventually for evaluating the risk of H. longicornis for transmitting the viruses to humans and animals. Video Abstract.


Assuntos
Ixodidae , Phlebovirus , Carrapatos , Animais , Humanos , Ixodidae/genética , Haemaphysalis longicornis , Viroma/genética , Filogenia , Phlebovirus/genética
4.
Gels ; 10(2)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38391450

RESUMO

Aerogels prepared using freeze-drying methods have the potential to be insulation materials or absorbents in the fields of industry, architecture, agriculture, etc., for their low heat conductivity, high specific area, low density, degradability, and low cost. However, their native, poor water resistance caused by the hydrophilicity of their polymer matrix limits their practical application. In this work, a novel, controllable, and efficient templating method was utilized to construct a highly hydrophobic surface for freeze-drying aerogels. The influence of templates on the macroscopic morphology and hydrophobic properties of materials was investigated in detail. This method provided the economical and rapid preparation of a water-resistant aerogel made from polyvinyl alcohol (PVA) and montmorillonite (MMT), putting forward a new direction for the research and development of new, environmentally friendly materials.

5.
Int J Nanomedicine ; 19: 1273-1285, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38348176

RESUMO

Purpose: To investigate the inhibition of Streptococcus mutans (S.mutans) and its biofilm by AgBr-nanoparticles (NP) @CTMAB (cetyltrimethyl-ammonium bromide) and evaluate the changes in Polymethyl methacrylate (PMMA)'s surface roughness (Ra), microhardness, and flexural strength during prolonged immersion in AgBr-NP@CTMAB for application in the denture cleaning industry. Patients and Methods: The antibacterial activity of AgBr-NP@CTMAB against S.mutans was measured colony formation assay, OD600 and laser confocal microscopy. Changes in the specimens' values for surface roughness, microhardness, and flexural strength (MPa) were measured after immersion solutions for 180 or 360 days. Results: The AgBr-NP@CTMAB solution exhibited a robust antibacterial effect on planktonic S. mutans, with a minimum bactericidal concentration of 5 µg/mL. The 10 µg/mL AgBr-NP@CTMAB solution efficiently inhibited S. mutans biofilm formation. (2) No significant difference in surface roughness after immersion in AgBr-NP@CTMAB (10 µg/mL and 20 µg/mL) comparing with distilled water (P > 0.05) and Polident had significantly higher than distilled water (P < 0.05). There was a significant decrease in the surface hardness of the PMMA specimens that were immersed in the Polident compared with those in distilled water (P < 0.05). While, no significant differences in surface hardness after immersion in the AgBr-NP@CTMAB (P > 0.05). The result of flexural strength suggested that there was no statistically significant difference (P < 0.05) between AgBr-NP@CTMAB as well as Polident and water. Conclusion: AgBrNP@CTMAB can efficiently inhibit the growth of plankton S.mutans and biofilm formation, without affecting the flexural strength, microhardness, or surface roughness of PMMA. Therefore, AgBrNP@CTMAB holds promise as a new denture cleaning agent.


Assuntos
Boratos , Nanopartículas , Polimetil Metacrilato , Sulfatos , Dureza , Resistência à Flexão , Streptococcus mutans , Bases de Dentadura , Água , Antibacterianos/farmacologia , Propriedades de Superfície , Teste de Materiais
6.
J Inflamm Res ; 17: 211-222, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38229692

RESUMO

Purpose: To characterize the cytokine profile of patients with severe fever with thrombocytopenia syndrome (SFTS) in relation to disease severity. Patients and Methods: 60 laboratory-confirmed SFTS patients and 12 healthy individuals from multi-centers in Shandong Province of China were included, and all patients were divided into fatal patients (9) and recovered patients (51) due to their final outcomes. Multiplex-microbead immunoassays were conducted to estimate levels of 27 cytokines in the sera of patients and controls. Results: The results showed that levels of IL-2, IL-4, IL-6, IL-7, IL-8, IL-15, IL-1RA, G-CSF, GM-CSF, IFN-γ, TNF-α, basic FGF, PDGF-BB, RANTES, IP-10, MIP-1α, MIP-1ß, MCP-1, and Eotaxin differed significantly among the SFTS fatal patients, recovered patients, and the healthy controls (all p<0.05). Compared to the healthy controls, the fatal patients and recovered patients had reduced levels of IL-2, IL-4, IL-7, PDGF-BB, RANTES, and Eotaxin, while the levels of PDGF-BB and RANTES were significantly lower in fatal patients compared to recovered patients. The increasing levels of IL-6, IL-8, IL-15, IL-1RA, G-CSF, GM-CSF, IFN-γ, TNF-α, basic FGF, IP-10, MIP-1α, MIP-1ß, and MCP-1 were observed in fatal patients (all p<0.05), and the levels of IL-6, IP-10, MIP-1α, and MCP-1 were significantly higher than other two groups. The Spearman correlation analysis indicated a positive correlation between platelet count and PDGF-BB levels (p<0.05), while the white blood cell count had a negative correlation with MIP-1 level (p<0.05). Conclusion: The research exhibited that the SFTS virus (SFTSV) caused an atypical manifestation of cytokines. The levels of IL-6, IP-10, MIP-1α, and MCP-1 had been observed a positive association with the severity of the illness.

7.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1005363

RESUMO

Based on WANG Xugao's “thirty methods of treating the liver”, it is believed that the occurrence and development of childhood tic disorders follow the dynamic progression from liver qi disease to liver fire disease and then liver wind disease. The basic pathogenesis of three stages are characterized by binding constraint of liver qi, liver fire hyperactivity, and internal stirring of liver wind. Moreover, liver-blood deficiency and stagnation, and malnutrition of liver yin as the main point in terms of the imbalance of liver qi, blood, yin, and yang should be considered, as well as the imbalance relationship of the five zang organs such as the involvement of other organs and the gradually reach of the other organs. Guided by the principles of “thirty methods of treating the liver”, the treatment of tic disorders in liver qi stage should focus on soothing the liver and rectifying qi, soothing the liver and unblocking the collaterals, using Xiaochaihu Decoction (小柴胡汤) and Sini Powder (四逆散). The treatment of tic disorders in liver fire stage involves clearing, draining and resolving liver heat, using Longdan Xiegan Decoction (龙胆泻肝汤), Xieqing Pill (泻青丸), Danggui Longhui Pill (当归龙荟丸), and Huagan Decoction (化肝煎). The treatment of tic disorders in liver wind stage involves extinguishing wind and subduing yang, using Lingjiao Gouteng Decoction (羚角钩藤汤) and Liuwei Dihuang Pill (六味地黄丸). Throughout the treatment process, attention should be paid to harmonizing the liver's qi, blood, yin, and yang, as well as addressing the pathology of other organs.

8.
Clin Oral Investig ; 28(1): 64, 2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-38158464

RESUMO

OBJECTIVES: This study aimed to investigate the functions of 19 types of Wnt ligands during the process of osteogenic differentiation in human periodontal ligament stem cells (hPDLSCs), with particular attention to WNT3A and WNT4. MATERIALS AND METHODS: The expression levels of 19 types of Wnt ligands were examined using real-time quantitative polymerase chain reaction (real-time qPCR) during hPDLSCs osteogenic differentiation at 7, 10, and 14 days. Knockdown of WNT3A and WNT4 expression was achieved using adenovirus vectors, and conditioned medium derived from WNT3A and WNT4 overexpression plasmids was employed to investigate their roles in hPDLSCs osteogenesis. Osteogenic-specific genes were analyzed using real-time qPCR. Alkaline phosphatase (ALP) and alizarin red S activities and staining were employed to assess hPDLSCs' osteogenic differentiation ability. RESULTS: During hPDLSCs osteogenic differentiation, the expression of 19 types of Wnt ligands varied, with WNT3A and WNT4 showing significant upregulation. Inhibiting WNT3A and WNT4 expression hindered hPDLSCs' osteogenic capacity. Conditioned medium of WNT3A promoted early osteogenic differentiation, while WNT4 facilitated late osteogenesis slightly. CONCLUSION: Wnt ligands, particularly WNT3A and WNT4, play an important role in hPDLSCs' osteogenic differentiation, highlighting their potential as promoters of osteogenesis. CLINICAL RELEVANCE: Given the challenging nature of alveolar bone regeneration, therapeutic strategies that target WNT3A and WNT4 signaling pathways offer promising opportunities. Additionally, innovative gene therapy approaches aimed at regulating of WNT3A and WNT4 expression hold potential for improving alveolar bone regeneration outcomes.


Assuntos
Osteogênese , Ligamento Periodontal , Humanos , Osteogênese/genética , Meios de Cultivo Condicionados/farmacologia , Meios de Cultivo Condicionados/metabolismo , Células-Tronco , Diferenciação Celular/genética , Células Cultivadas
9.
Front Cell Dev Biol ; 11: 1282119, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38033870

RESUMO

Most mammals tolerate exposure to hypobaric hypoxia poorly as it may affect multiple regulatory mechanisms and inhibit cell proliferation, promote apoptosis, limit tissue vascularization, and disrupt the acid-base equilibrium. Here, we quantified the functional state of germ cell development and demonstrated the interaction between the germ and somatic cells via single-cell RNA sequencing (scRNA-seq). The present study elucidated the regulatory effects of hypobaric hypoxia exposure on germ cell formation and sperm differentiation by applying enrichment analysis to genomic regions. Hypobaric hypoxia downregulates the genes controlling granule secretion and organic matter biosynthesis, upregulates tektin 1 (TEKT1) and kinesin family member 2C (KIF2C), and downregulates 60S ribosomal protein 11 (RPL11) and cilia- and flagella-associated protein 206 (CFAP206). Our research indicated that prosaposin-G protein-coupled receptor 37 (PSAP-GPR37) ligands mediate the damage to supporting cells caused by hypobaric hypoxic exposure. The present work revealed that hypoxia injures peritubular myoid (PTM) cells and spermatocytes in the S phase. It also showed that elongating spermatids promote maturation toward the G2 phase and increase their functional reserve for sperm-egg binding. The results of this study provide a theoretical basis for future investigations on prophylactic and therapeutic approaches toward protecting the reproductive system against the harmful effects of hypobaric hypoxic exposure.

10.
World J Clin Cases ; 11(30): 7302-7308, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37969451

RESUMO

BACKGROUND: Carbapenem antibiotics are a pivotal solution for severe infections, particularly in hospital settings. The emergence of carbapenem-resistant bacteria owing to the irrational and extensive use of carbapenems underscores the need for meticulous management and rational use. Clinical pharmacists, with their specialized training and extensive knowledge, play a substantial role in ensuring the judicious use of carbapenem. This study aimed to elucidate the patterns of carbapenem use and shed light on the integral role played by clinical pharmacists in managing and promoting the rational use of carbapenem antibiotics at Wenzhou Integrated Traditional Chinese and Western Medicine Hospital. AIM: To analyze carbapenem use patterns in our hospital and role of clinical pharmacists in managing and promoting their rational use. METHODS: We performed a retrospective analysis of carbapenem use at our hospital between January 2019 and December 2021. Several key indicators, including the drug utilization index, defined daily doses (DDDs), proportion of antimicrobial drug costs to total hospitalization expenses, antibiotic utilization density, and utilization rates in different clinical departments were comprehensively analyzed. RESULTS: Between 2019 and 2021, there was a consistent decline in the consumption and sales of imipenem-cilastatin sodium, meropenem (0.3 g), and meropenem (0.5 g). Conversely, the DDDs of imipenem-cilastatin sodium for injection increased in 2020 and 2021 vs 2019, with a B/A value of 0.67, indicating a relatively higher drug cost. The DDDs of meropenem for injection (0.3 g) exhibited an overall upward trend, indicating an increasing clinical preference. However, the B/A values for 2020 and 2021 were both > 1, suggesting a relatively lower drug cost. The DDDs of meropenem for injection (0.5 g) demonstrated a progressive increase annually and consistently ranked first, indicating a high clinical preference with a B/A value of 1, signifying good alignment between economic and social benefits. CONCLUSION: Carbapenem use in our hospital was generally reasonable with a downward trend in consumption and sales over time. Clinical pharmacists play a pivotal role in promoting appropriate use of carbapenems.

11.
Chem Biodivers ; 20(11): e202301507, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37847218

RESUMO

One new alkaloid, (S)-2-acetamido-4-(2-(methylamino)phenyl)-4-oxobutanoic acid (1), was isolated from the deep-sea-derived Penicillium citrinum XIA-16, together with 25 known compounds including ten polyketones (2-11), eight alkaloids (12-19), six steroids (20-25), and a fatty acid (26). Their planar and relative structures were determined by an analysis of 1D and 2D nuclear magnetic resonance (NMR) as well as high resolution electrospray ionization mass spectroscopy (HR-ESI-MS) data. The absolute configuration of 1 was determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Penicitrinol B (6) significantly inhibited RSL3-induced ferroptosis (EC50 =2.0 µM) by reducing lipid peroxidation and heme oxygenase 1 (HMOX1) expression. Under the concentration of 10 µM, penicitrinol A (7) was able to inhibit cuproptosis with the cell viabilities of 68.2 % compared to the negative control (copper and elesclomol) with the cell viabilities of 14.8 %.


Assuntos
Alcaloides , Antineoplásicos , Penicillium , Animais , Penicillium/química , Antineoplásicos/farmacologia , Espectroscopia de Ressonância Magnética/métodos , Alcaloides/química , Crustáceos , Estrutura Molecular
12.
Zool Res ; 44(6): 993-1002, 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37759334

RESUMO

Targeting key enzymes that generate oxalate precursors or substrates is an alternative strategy to eliminate primary hyperoxaluria type I (PH1), the most common and life-threatening type of primary hyperoxaluria. The compact Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) from the Prevotella and Francisella 1 (Cpf1) protein simplifies multiplex gene editing and allows for all-in-one adeno-associated virus (AAV) delivery. We hypothesized that the multiplex capabilities of the Cpf1 system could help minimize oxalate formation in PH1 by simultaneously targeting the hepatic hydroxyacid oxidase 1 ( Hao1) and lactate dehydrogenase A ( Ldha) genes. Study cohorts included treated PH1 rats ( Agxt Q84X rats injected with AAV-AsCpf1 at 7 days of age), phosphate-buffered saline (PBS)-injected PH1 rats, untreated PH1 rats, and age-matched wild-type (WT) rats. The most efficient and specific CRISPR RNA (crRNA) pairs targeting the rat Hao1 and Ldha genes were initially screened ex vivo. In vivo experiments demonstrated efficient genome editing of the Hao1 and Ldha genes, primarily resulting in small deletions. This resulted in decreased transcription and translational expression of Hao1 and Ldha. Treatment significantly reduced urine oxalate levels, reduced kidney damage, and alleviated nephrocalcinosis in rats with PH1. No liver toxicity, ex-liver genome editing, or obvious off-target effects were detected. We demonstrated the AAV-AsCpf1 system can target multiple genes and rescue the pathogenic phenotype in PH1, serving as a proof-of-concept for the development of multiplex genome editing-based gene therapy.


Assuntos
Hiperoxalúria Primária , Animais , Ratos , Edição de Genes/métodos , Edição de Genes/veterinária , Hiperoxalúria Primária/genética , Hiperoxalúria Primária/terapia , Hiperoxalúria Primária/veterinária , Fígado , Oxalatos
13.
Surg Laparosc Endosc Percutan Tech ; 33(6): 673-681, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37750709

RESUMO

BACKGROUND: To systematically evaluate the methodological quality of the current up-to-date guidelines pertaining to choledocholithiasis, we conducted a comprehensive analysis of key recommendations and corresponding evidence, focusing on the heterogeneity among these guidelines. METHOD: Systematic searches across various databases were performed to identify the latest guidelines. The identified guidelines, which met the inclusion criteria, underwent evaluation using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. The key recommendations and evidence from the included guidelines were extracted and reclassified using the Oxford Centre for Evidence-Based Medicine (OCEBM) grading system, and the obtained results were analyzed. RESULTS: Nine guidelines related to choledocholithiasis were included in this study, out of which 4 achieved an overall standardized score of more than 60%, indicating their suitability for recommendation. Upon closer examination of the main recommendations within these guidelines, we discovered significant discrepancies concerning the utilization of similar treatment techniques for different diseases or different treatment methods under comparable conditions, and discrepancies in the recommended treatment duration. High-quality research evidence was lacking, and some recommendations either failed to provide supporting evidence or cited inappropriate and low-level evidence. CONCLUSION: The quality of guidelines pertaining to choledocholithiasis is uneven. Recommendations for the treatment of choledocholithiasis demonstrate considerable disparities among the guidelines, particularly regarding the utilization of endoscopic retrograde cholangiopancreatography as a treatment method and the management approaches for difficult stone cases. Improvements by guideline developers for these factors contributing to the heterogeneity would be a reasonable approach to further update the guidelines for cholangiolithiasis.


Assuntos
Coledocolitíase , Guias de Prática Clínica como Assunto , Humanos , Coledocolitíase/diagnóstico , Coledocolitíase/cirurgia , Medicina Baseada em Evidências , Guias de Prática Clínica como Assunto/normas
14.
Rheumatol Adv Pract ; 7(2): rkad064, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37547578

RESUMO

Objectives: The surge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron infections has affected most Chinese residents at the end of 2022, including a number of patients with systemic autoimmune rheumatic diseases (SARDs). Methods: To investigate the antibody level of the Omicron variant in SARD patients after SARS-CoV-2 Omicron infection, we tested BA.5.2 and BF.7 Omicron variant IgG antibody levels using ELISA on blood samples collected from 102 SARD patients and 19 healthy controls (HCs). The type of SARD, demographics, concurrent treatment, doses of SARS-CoV-2 vaccines and outcomes were also recorded. Results: A total of 102 SARD patients (mean age: 40.3 years; 89.2% female), including 60 SLE, 32 RA and 10 other SARDs, were identified. Of these, 87 (85.3%) were infected with SARS-CoV-2. We found that the BA.5.2 and BF.7 antibody levels of infected SARD patients were lower than those of HCs (P < 0.05). Sixty-five (63.7%) patients had at least one dose of a SARS-CoV-2 vaccine. SARD patients with at least two doses of SARS-CoV-2 vaccine had a higher level of BA.5.2 and BF.7 antibodies than the unvaccinated group (P < 0.05). There was no evidence for a significant inhibitory effect of glucocorticoids (GCs) on the BA.5.2 and BF.7 Omicron variant antibody levels in SARD patients. SLE patients using biologic DMARDs had a lower BA.5.2 Omicron variant antibody level than patients using GCs and/or HCQ. Conclusion: These data suggest that patients with SARDs had a lower antibody response than HCs after Omicron infection.

15.
Phytomedicine ; 118: 154951, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37453193

RESUMO

BACKGROUND: Hypertension has seriously affected a large part of the adult and elderly population. The complications caused by hypertension are important risk factors for cardiovascular disease accidents. Capsaicin, a pungent component of chili pepper has been revealed to improve hypertension. However, its potential mechanism in improving hypertension remains to be explored. PURPOSE: In the present study, we aimed to investigate whether capsaicin could attenuate the SIRT1/NF-κB/MAPKs pathway in the paraventricular nucleus of hypothalamus (PVN). METHODS: We used spontaneous hypertensive rats (SHRs) as animal model rats. Micro osmotic pump was used to give capsaicin through PVN for 28 days, starting from age12-week-old. RESULTS: The results showed that capsaicin significantly reduced blood pressure from the 16th day of infusion onward. At the end of the experimental period, we measured cardiac hypertrophy index and the heart rate (HR), and the results showed that the cardiac hypertrophy and heart rate of rats was significantly improved upon capsaicin chronic infusion. Norepinephrine (NE) and epinephrine (EPI) in plasma of SHRs treated with capsaicin were also decreased. Additionally, capsaicin increased the protein expression and number of positive cells of SIRT1 and the 67-kDa isoform of glutamate decarboxylase (GAD67), decreased the production of reactive oxygen species (ROS), number of positive cells of NOX2, those of Angiotensin Converting Enzyme (ACE) and p-IKKß, tyrosine hydroxylase (TH), the gene expression levels of NOX4 and pro-inflammatory cytokines. Capsaicin also decreased the relative protein expressions of protein in MAPKs pathway. CONCLUSION: Current data indicated that capsaicin within the PVN improves hypertension and cardiac hypertrophy via SIRT1/NF-κB/MAPKs pathway in the PVN of SHRs, supporting its potential as candidate drug for preventing and improving hypertension.


Assuntos
Hipertensão , NF-kappa B , Idoso , Humanos , Ratos , Animais , NF-kappa B/metabolismo , Núcleo Hipotalâmico Paraventricular , Capsaicina/farmacologia , Sirtuína 1/metabolismo , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Cardiomegalia/tratamento farmacológico , Cardiomegalia/metabolismo , Ratos Endogâmicos SHR
16.
Acta Pharmacol Sin ; 44(12): 2492-2503, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37468692

RESUMO

Endothelial dysfunction, a central hallmark of cardiovascular pathogenesis in diabetes mellitus, is characterized by impaired endothelial nitric oxide synthase (eNOS) and NO bioavailability. However, the underlying mechanisms remain unclear. Here in this study, we aimed to identify the role of calmodulin (CaM) in diabetic eNOS dysfunction. Human umbilical vein endothelial cells and murine endothelial progenitor cells (EPCs) treated with high glucose (HG) exhibited downregulated CaM mRNA/protein and vascular endothelial growth factor (VEGF) expression with impeded eNOS phosphorylation and cell migration/tube formation. These perturbations were reduplicated in CALM1-knockdown cells but prevented in CALM1-overexpressing cells. EPCs from type 2 diabetes animals behaved similarly to HG-treated normal EPCs, which could be rescued by CALM1-gene transduction. Consistently, diabetic animals displayed impaired eNOS phosphorylation, endothelium-dependent dilation, and CaM expression in the aorta, as well as deficient physical interaction of CaM and eNOS in the gastrocnemius. Local CALM1 gene delivery into a diabetic mouse ischemic hindlimb improved the blunted limb blood perfusion and gastrocnemius angiogenesis, and foot injuries. Diabetic patients showed insufficient foot microvascular autoregulation, eNOS phosphorylation, and NO production with downregulated CaM expression in the arterial endothelium, and abnormal CALM1 transcription in genome-wide sequencing analysis. Therefore, our findings demonstrated that downregulated CaM expression is responsible for endothelium dysfunction and angiogenesis impairment in diabetes, and provided a novel mechanism and target to protect against diabetic endothelial injury.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Camundongos , Animais , Diabetes Mellitus Tipo 2/metabolismo , Calmodulina/genética , Calmodulina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Endotélio/metabolismo , Isquemia/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Neovascularização Fisiológica
17.
World J Psychiatry ; 13(5): 191-202, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37303933

RESUMO

BACKGROUND: The teaching mode of fitness exercise prescriptions for college students in physical education conforms to the scientific principles and rules of fitness, which can adapt to the characteristics of students' individual physiological functions and stimulate their interest in learning. AIM: To analyze the effect of prescribed exercise teaching on the sports quality and mental health of college students. METHODS: The participants of the study were 240 students in our class of 2021, of which 142 were men and 98 were women. The 240 students were randomly divided into an experimental group using the exercise prescription teaching model and a control group using the conventional teaching model. The experimental and control groups were divided into four classes of 30 students each. The teaching activities of the two teaching mode groups were strictly controlled, and the same tests were used before and after the experiment to test the subjects' exercise quality (in-cluding standing long jump, 50 m race, 800 m race, sit-ups, sit-and-reach), physical form (including height, weight, Ketorolai index), cardiopulmonary function (including heart rate, blood pressure, spirometry, 12-min running distance, maximum oxygen intake) and mental health (SCL-90, including somatization, obsessive-compulsive, interpersonal, depression, anxiety, hostility, phobia, paranoia, psychotic symptoms) to understand the effects of the exercise prescription teaching mode on students' physical and mental health status. RESULTS: There were differences in the exercise scores of standing long jump, 50 m, 800 m/1000 m running, sit-ups, and sit-and-reach in the experimental group after the experiment compared with those before the experiment, and the above indices of the experimental group were different from those of the control group after the experiment (P < 0.05). There were differences in body weight and Ketorolai index in the experimental group after the experiment compared to those before the experiment, and the indices of the experimental group were also different from those of the control group after the experiment (P < 0.05). After the experiment, there were differences in spirometry, 12-min running distance, and maximum oxygen intake in the experimental group compared to those before the experiment, and the indices of the experimental group were also different from those of the control group after the experiment (P < 0.05). After the experiment, the indicators of somatization, interpersonal sensitivity, depression, anxiety, and hostility in the experimental group were different from those in the pre-experimental group, and the indexes of the experimental group were also different from those of the control group after the experiment (P < 0.05). CONCLUSION: Exercise prescription teaching can mobilize college students' consciousness, enthusiasm, and initiative; expand personalities; enhance physical fitness and improve their mental health more than the conventional fitness exercise prescription teaching method.

18.
Inorg Chem ; 62(20): 7681-7688, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37148562

RESUMO

Rare-earth (RE) chalcogenide borates are very rarely discovered in view of the difficulties in synthesis though they have demonstrated attractive physical performances. Here, the first mixed RE chalcogenide borates Eu5.4Sm3.6MgS2B20O41 (1) and Eu3Gd6MgS2B20O41 (2) are synthesized by combining RE, sulfur, and borate ions into one structure. They crystallize in the centrosymmetric hexagonal space group P63/m, and their 3D honeycomb-like {[B20O41]22-}∞ open frameworks are built by [B6O9(O0.5)6]6- and [B7O13(O0.5)3]8- polyanionic clusters and consolidated by Mg2+ ions; both of which are formed by BO4 tetrahedra and BO3 planar triangles. The coordination modes of RE ions are rare REO6S2 bicapped trigonal prisms and REO8S irregular polyhedra, and their band gaps are determined to be 2.25 and 2.22 eV, respectively. They exhibit antiferromagnetic interactions and distinct photocurrent responses. The corresponding theoretical calculations are also performed. The study of 1 and 2 perhaps stimulates interest in exploring new functional RE chalcogenide borates.

19.
BMC Oral Health ; 23(1): 329, 2023 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-37237299

RESUMO

BACKGROUND: The cadherin-4 gene (CDH4), a member of the cadherin family genes, encodes R-cadherin (R-cad); however, the function of this gene in different types of cancer remains controversial. The function of CDH4 in OSCC (oral squamous cell carcinoma) is unknown. MATERIALS AND METHODS: We use the Cancer Genome Atlas (TCGA) database to find the expression of CDH4 in OSCC is more than normal tissue. Our tissue samples also confirmed that CDH4 gene was highly expressed in OSCC. The related cell function assay detected that CDH4 promotes the ability of cell proliferation, migration, self-renewal and invasion. Cell staining experiment confirmed that the change of CDH4 expression would change the cell mortality. The western blot of GPX4 (glutathione-dependent peroxidase-4), GSH (reduced glutathione) test assay and MDA(Malondialdehyde) test assay show that the expression of CDH4 may resist the sensitivity of ferropotosis in OSCC. RESULTS: CDH4 was upregulated in OSCC samples and was correlation with poor survival of patients. High expression of CDH4 effectively promotes the proliferation, mobility of OSCC cells and reduce the sensitivity of OSCC cells to ferroptosis. CDH4 is positively correlated with EMT pathway genes, negatively correlated with fatty acid metabolism pathway genes and peroxisome pathway genes, and positively correlated with ferroptosis suppressor genes in OSCC. CONCLUSIONS: These results indicate that CDH4 may play a positive role in tumor progression and resistance ferroptosis and may be a potential therapeutic target for OSCC.


Assuntos
Caderinas , Ferroptose , Neoplasias Bucais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Caderinas/genética
20.
iScience ; 26(6): 106831, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37250791

RESUMO

This study aims to identify biomarkers of intestinal repair and provide potential therapeutic clues for improving functional recovery and prognostic performance after intestinal inflammation or injury. Here, we conducted a large-scale screening of multiple transcriptomic and scRNA-seq datasets of patients with inflammatory bowel disease (IBD), and identified 10 marker genes that potentially contribute to intestinal barrier repairing: AQP8, SULT1A1, HSD17B2, PADI2, SLC26A2, SELENBP1, FAM162A, TNNC2, ACADS, and TST. Analysis of a published scRNA-seq dataset revealed that expression of these healing markers were specific to absorptive cell types in intestinal epithelium. Furthermore, we conducted a clinical study where 11 patients underwent ileum resection demonstrating that upregulation of post-operative AQP8 and SULT1A1 expression were associated with improved recovery of bowel functions after surgery-induced intestinal injury, making them confident biomarkers of intestinal healing as well as potential prognostic markers and therapeutic targets for patients with impaired intestinal barrier functions.

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