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1.
Artigo em Inglês | MEDLINE | ID: mdl-39300709

RESUMO

Cervical cancer (CC) poses a threat to human health. Enhancing pyroptosis can prevent the proliferation and epithelial-mesenchymal transition (EMT) of tumor cells. This study aims to reveal the candidates that modulate pyroptosis in CC. Accordingly, the common microRNAs (miRNAs/miRs) that were sponged by RBPMS antisense RNA 1 (RBPMS-AS1) and could target Phospholipase C-Like 1 (PLCL1) were intersected. The expression of PBPMS-AS1/miR-19a-3p (candidate miRNA)/PLCL1 was predicted in cervical squamous cell carcinoma (CESC), by which the expression location of RBPMS-AS1 and the binding between RBPMS-AS1/PLCL1 and miR-19a-3p were analyzed. The targeting relationship between RBPMS-AS1/PLCL1 and miR-19a-3p was confirmed by dual-luciferase reporter assay. After the transfection, cell counting kit-8 assay, colony formation assay, quantitative reverse transcription PCR, and Western blot were implemented for cell viability and proliferation analysis as well as gene and protein expression quantification analysis. Based on the results, RBPMS-AS1 and PLCL1 were lowly expressed, yet miR-19a-3p was highly expressed in CESC. RBPMS-AS1 overexpression diminished the proliferation and expressions of N-cadherin, vimentin, and miR-19a-3p, yet enhanced those of E-cadherin, PLCL1, and pyroptosis-relevant proteins (inteleukin-1ß, caspase-1, and gasdermin D N-terminal). However, the above RBPMS-AS1 overexpression-induced effects were counteracted in the presence of miR-19a-3p. There also existed a targeting relationship and negative interplay between PLCL1 and miR-19a-3p. In short, RBPMS-AS1 sponges miR-19a-3p and represses the growth and EMT of CC cells via enhancing PLCL1-mediated pyroptosis.

2.
BMC Vet Res ; 20(1): 421, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39304865

RESUMO

BACKGROUND: Mycoplasmal pneumonia of sheep and goats (MPSG) is an important infectious disease that threatens sheep and goat production worldwide, and Mycoplasma ovipneumoniae (Movi) is one of the major aetiological agents causing MPSG. The aim of this study was to investigate the immunological activity of the Hsp70‒P113 fusion protein derived from Movi and to develop a serological assay for the detection of Movi. METHODS: This study involved codon optimization of the dominant antigenic regions of Movi heat shock protein 70 (Hsp70) and adhesin P113. Afterwards, the optimized sequences were inserted into the prokaryotic expression vector pET-30a( +) through tandem linking with the aid of a linker. Once a positive recombinant plasmid (pET-30a-rHsp70-P113) was successfully generated, the expression conditions were further refined. The resulting double gene fusion target protein (rHsp70‒P113) was subsequently purified using ProteinIso® Ni-NTA resin, and the reactivity of the protein was confirmed via SDS‒PAGE and Western blot analysis. An indirect enzyme-linked immunosorbent assay (i-ELISA) technique was developed to detect Movi utilizing the fusion protein as the coating antigen. The specificity, sensitivity, and reproducibility of all methods were assessed after each reaction parameter was optimized. RESULTS: The resulting rHsp70-P113 protein had a molecular weight of approximately 51 kDa and was predominantly expressed in the supernatant. Western blot analysis demonstrated its favourable reactivity. The optimal parameters for the i-ELISA technique were as follows: the rHsp70-P113 protein was encapsulated at a concentration of 5 µg/mL; the serum was diluted at a ratio of 1:50; the HRP-labelled donkey anti-goat IgG was diluted at a ratio of 1:6,000. The results of the cross-reactivity assays revealed that the i-ELISA was not cross-reactive with other goat-positive sera against Mycoplasma mycodies subsp. capri (Mmc), Mycoplasma capricolum subsp. capripneumoniae (Mccp), Mycoplasma arginini (Marg), orf virus (ORFV) or enzootic nasal tumour virus of goats (ENTV-2). The sensitivity of this method is high, with a maximum dilution of up to 1:640. The results of the intra- and inter-batch replication tests revealed that the coefficients of variation were both less than 10%, indicating excellent reproducibility. The analysis of 108 clinical serum samples via i-ELISA and indirect haemagglutination techniques yielded significant findings. Among these samples, 43 displayed positive results, whereas 65 presented negative results, resulting in a positivity rate of 39.8% for the i-ELISA method. In contrast, the indirect haemagglutination technique identified 20 positive samples and 88 negative samples, resulting in a positivity rate of 18.5%. Moreover, a comparison between the two methods revealed a conformity rate of 78.7%. CONCLUSION: The results obtained in this study lay the groundwork for advancements in the use of an Movi antibody detection kit, epidemiological inquiry, and subunit vaccines.


Assuntos
Ensaio de Imunoadsorção Enzimática , Doenças das Cabras , Cabras , Proteínas de Choque Térmico HSP70 , Mycoplasma ovipneumoniae , Pneumonia por Mycoplasma , Proteínas Recombinantes de Fusão , Doenças dos Ovinos , Animais , Mycoplasma ovipneumoniae/imunologia , Mycoplasma ovipneumoniae/genética , Proteínas de Choque Térmico HSP70/imunologia , Proteínas de Choque Térmico HSP70/genética , Doenças das Cabras/diagnóstico , Doenças das Cabras/imunologia , Doenças das Cabras/microbiologia , Ensaio de Imunoadsorção Enzimática/veterinária , Ensaio de Imunoadsorção Enzimática/métodos , Doenças dos Ovinos/imunologia , Doenças dos Ovinos/diagnóstico , Doenças dos Ovinos/microbiologia , Ovinos , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/genética , Pneumonia por Mycoplasma/veterinária , Pneumonia por Mycoplasma/diagnóstico , Pneumonia por Mycoplasma/imunologia , Adesinas Bacterianas/imunologia , Adesinas Bacterianas/genética , Anticorpos Antibacterianos/sangue , Sensibilidade e Especificidade , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/genética
3.
J Orthop Surg Res ; 19(1): 572, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39285416

RESUMO

BACKGROUND: Osteoporosis results from decreased bone mass and disturbed bone structure. Human bone marrow mesenchymal stem cells (hBMSCs) demonstrate robust osteogenic differentiation, a critical process for bone formation. This research was designed to examine the functions of LINC01133 in osteogenic differentiation. METHODS: Differentially expressed lncRNAs affecting osteogenic differentiation in hBMSCs were identified from the GEO database. A total of 74 osteoporosis patients and 70 controls were enrolled. hBMSCs were stimulated to undergo osteogenic differentiation using an osteogenic differentiation medium (OM). RT-qPCR was performed to evaluate LINC01133 levels and osteogenesis-related genes such as osteocalcin, osteopontin, and RUNX2. An alkaline phosphates (ALP) activity assay was conducted to assess osteogenic differentiation. Cell apoptosis was detected using flow cytometry. Dual luciferase reporter assay and RIP assay were employed to investigate the association between miR-214-3p and LINC01133 or CTNNB1. Loss or gain of function assays were conducted to elucidate the impact of LINC01133 and miR-214-3p on osteogenic differentiation of hBMSCs. RESULTS: LINC01133 and CTNNB1 expression decreased in osteoporotic patients but increased in OM-cultured hBMSCs, whereas miR-214-3p showed an opposite trend. Depletion of LINC01133 suppressed the expression of genes associated with bone formation and ALP activity triggered by OM in hBMSCs, leading to increased cell apoptosis. Nevertheless, this suppression was partially counteracted by the reduced miR-214-3p levels. Mechanistically, LINC01133 and CTNNB1 were identified as direct targets of miR-214-3p. CONCLUSIONS: Our study highlights the role of LINC01133 in positively regulating CTNNB1 expression by inhibiting miR-214-3p, thereby promoting osteogenic differentiation of BMSCs. These findings may provide valuable insights into bone regeneration in osteoporosis.


Assuntos
Diferenciação Celular , Células-Tronco Mesenquimais , MicroRNAs , Osteogênese , Osteoporose , RNA Longo não Codificante , Regulação para Cima , beta Catenina , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Células-Tronco Mesenquimais/metabolismo , Osteogênese/genética , Osteogênese/fisiologia , Diferenciação Celular/genética , RNA Longo não Codificante/genética , beta Catenina/genética , beta Catenina/metabolismo , Osteoporose/genética , Osteoporose/metabolismo , Osteoporose/patologia , Células Cultivadas , Feminino , Pessoa de Meia-Idade , Masculino , Apoptose/genética , Células da Medula Óssea/metabolismo
4.
J Orthop Surg Res ; 19(1): 466, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39118176

RESUMO

OBJECTIVE: Delayed fracture healing increases the suffering of patients. An in-depth investigation of the pathogenesis of delayed fracture healing may offer new direction for the prevention and treatment. METHODS: The study included 63 normal healing tibial fractures and 58 delayed healing tibial fractures patients. Long non-coding RNA (lncRNA)TRPM2-AS, microRNA-545-3p (miR-545-3p), bone morphogenetic protein 2 (Bmp2) mRNA and osteogenic differentiation markers, including runt-related transcription factor 2 (Runx2), osteocalcin (Ocn), and alkaline phosphatase (Alp) mRNA expression were determined by Real-time quantitative reverse transcription-polymerase chain reaction in serum and MC3T3-E1 cells. The prediction potential of TRPM2-AS in delayed healing fracture patients was verified by receiver operating characteristic curves. The binding relationship of TRPM2-AS/miR-545-3p/Bmp2 was evaluated by dual luciferase reporter gene assay. Cell proliferation and apoptosis were detected by CCK-8 and flow cytometry. RESULTS: TRPM2-AS was remarkably down-regulated in patients with delayed fracture healing and could better predict the fracture healing status. TRPM2-AS downregulation inhibited osteogenic markers mRNA expression, restrained proliferation, and promoted apoptosis of MC3T3-E1 cells (p < 0.05). In delayed fracture healing, miR-545-3p was dramatically up-regulated and was negatively regulated by TRPM2-AS. Reducing miR-545-3p eliminate the negative effect of TRPM2-AS down-regulation on osteoblast proliferation and differentiation (p < 0.05). miR-545-3p targets Bmp2, which plays a positive role in osteoblast differentiation (p < 0.05). CONCLUSION: This study found that TRPM2-AS has the potential to be a diagnostic marker for delayed fracture healing and revealed that the TRPM2-AS/miR-545-3p/Bmp2 axis affects fracture healing by regulating osteoblast.


Assuntos
Proteína Morfogenética Óssea 2 , Consolidação da Fratura , MicroRNAs , Adulto , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Apoptose/genética , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/metabolismo , Diferenciação Celular/genética , Proliferação de Células/genética , Consolidação da Fratura/genética , Consolidação da Fratura/fisiologia , MicroRNAs/genética , Osteoblastos/metabolismo , Osteogênese/genética , Osteogênese/fisiologia , RNA Longo não Codificante/genética , Fraturas da Tíbia/genética , Canais de Cátion TRPM/genética
5.
Hemoglobin ; 48(3): 182-185, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-39103314

RESUMO

We reported a rare ß-thalassemia patient, a 41-year-old Chinese male with small cell hypopigmentation anemia, jaundice and splenomegaly as the main clinical symptoms. By using Next-Generation Sequencing (NGS), we identified a novel de novo HBB mutation(c.358_365dup, p.Phe123Alafs*39) which resulted in an abnormally prolonged ß-globin chain comprising 159 amino acid residues. The secondary and three-dimensional structures of the ß-globin predicted that the novel prolonged ß-globin chain has a considerable risk of instability in the hemoglobin, and leads to clinical phenotype. This study contributes to the enrichment of the genetic pathogenic mutation database for thalassemia and underscores the significance of NGS in the screening of mutations for thalassemia families.


Assuntos
Povo Asiático , Mutação da Fase de Leitura , Globinas beta , Talassemia beta , Humanos , Talassemia beta/genética , Talassemia beta/diagnóstico , Masculino , Globinas beta/genética , Adulto , Povo Asiático/genética , Sequenciamento de Nucleotídeos em Larga Escala , Fenótipo , População do Leste Asiático
6.
J Orthop Surg Res ; 19(1): 511, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39192334

RESUMO

OBJECTIVE: Delayed fracture healing is a common complication of fractures that significantly impacts human health. This study aimed to explore the role of LINC00339 (lncRNA) in delayed fracture healing to provide new directions for its treatment. METHODS: This study included 82 patients with fractures healing in a normal manner and 90 patients experiencing delayed fracture healing. Levels of LINC00339, miR-16-5p, and osteogenic marker-related mRNAs were measured using RT-qPCR. The predictive potential of LINC00339 for delayed fracture healing was validated using ROC curve analysis. The interaction between LINC00339 and miR-16-5p was validated using dual-luciferase reporter assays and RIP experiments. CCK-8 was used to assess cell proliferation, and apoptosis rates were measured by flow cytometry. RESULTS: LINC00339 was significantly upregulated in delayed fracture healing patients and exhibited strong predictive ability for this condition. Overexpression of LINC00339 inhibited osteoblast proliferation, promoted apoptosis, and reduced mRNA levels of osteogenic markers (P < 0.05). miR-16-5p was recognized as a target mRNA of LINC00339, with LINC00339 exerting negative regulation on miR-16-5p, while overexpression of miR-16-5p mitigated the inhibitory effects of LINC00339 on fracture healing (P < 0.05). CONCLUSION: This research indicated that LINC00339 may serve as a diagnostic marker for delayed fracture healing and revealed the function of the LINC00339/miR-16-5p axis on fracture healing by regulating osteoblasts.


Assuntos
Apoptose , Proliferação de Células , Consolidação da Fratura , MicroRNAs , RNA Longo não Codificante , Consolidação da Fratura/genética , Consolidação da Fratura/fisiologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Humanos , MicroRNAs/genética , Proliferação de Células/genética , Apoptose/genética , Masculino , Feminino , Osteoblastos/metabolismo , Osteogênese/genética , Osteogênese/fisiologia , Pessoa de Meia-Idade , Adulto , Regulação para Cima , Células Cultivadas
7.
Nutr J ; 23(1): 95, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39160579

RESUMO

BACKGROUND: The occurrence and progression of asthma can be influenced by the components in food. Our study aims to determine whether dietary antioxidant and inflammatory potential are associated with the risk of mortality in asthma patients. METHODS: Participants from the 2001-2018 National Health and Nutrition Examination Survey (NHANES) aged 20 years and older with a diagnosis of asthma were included. Mortality status was obtained according to death certificate records from the National Death Index. The antioxidant and inflammatory potential of the diet was assessed using two widely used and dependable indices, Composite Dietary Antioxidant Index (CDAI) and Dietary Inflammatory Index (DII). Restricted cubic spline (RCS) regression was used to analyze the non-linear relationship between the two indexes and mortality. Multivariable Cox proportional risk models were used to estimate hazard ratio and 95% confidence intervals for mortality. Finally, the relationship between CDAI and DII was analyzed. RESULTS: A total of 4698 NHANES participants represented 23.2 million non-institutionalized residents of the US were enrolled in our study. Patients with higher CDAI or lower DII exhibited longer survival times. RCS regression showed a linear relationship of CDAI or DII with mortality. In the Cox regression, both crude and adjusted models demonstrated that higher CDAI or lower DII was linked to a reduced risk of all-cause mortality. Similar associations were found in subgroup analysis. Finally, a negative relationship was found between CDAI and DII. CONCLUSION: Reducing pro-inflammatory or increasing antioxidant diets could reduce all-cause mortality among adult asthma patients.


Assuntos
Antioxidantes , Asma , Dieta , Inflamação , Inquéritos Nutricionais , Humanos , Asma/mortalidade , Feminino , Masculino , Antioxidantes/administração & dosagem , Antioxidantes/análise , Pessoa de Meia-Idade , Adulto , Inquéritos Nutricionais/estatística & dados numéricos , Inquéritos Nutricionais/métodos , Dieta/métodos , Dieta/estatística & dados numéricos , Inflamação/mortalidade , Estados Unidos/epidemiologia , Modelos de Riscos Proporcionais , Idoso , Adulto Jovem , Fatores de Risco
8.
Front Pharmacol ; 15: 1431941, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39206259

RESUMO

Agranulocytosis, induced by non-chemotherapy drugs, is a serious medical condition that presents a formidable challenge in predictive toxicology due to its idiosyncratic nature and complex mechanisms. In this study, we assembled a dataset of 759 compounds and applied a rigorous feature selection process prior to employing ensemble machine learning classifiers to forecast non-chemotherapy drug-induced agranulocytosis (NCDIA) toxicity. The balanced bagging classifier combined with a gradient boosting decision tree (BBC + GBDT), utilizing the combined descriptor set of DS and RDKit comprising 237 features, emerged as the top-performing model, with an external validation AUC of 0.9164, ACC of 83.55%, and MCC of 0.6095. The model's predictive reliability was further substantiated by an applicability domain analysis. Feature importance, assessed through permutation importance within the BBC + GBDT model, highlighted key molecular properties that significantly influence NCDIA toxicity. Additionally, 16 structural alerts identified by SARpy software further revealed potential molecular signatures associated with toxicity, enriching our understanding of the underlying mechanisms. We also applied the constructed models to assess the NCDIA toxicity of novel drugs approved by FDA. This study advances predictive toxicology by providing a framework to assess and mitigate agranulocytosis risks, ensuring the safety of pharmaceutical development and facilitating post-market surveillance of new drugs.

9.
Adv Sci (Weinh) ; : e2402086, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946582

RESUMO

Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences  is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched-chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high-fat diet/low-dose streptozotocin (HFD/STZ)-induced T2DM and leptin receptor-deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label-free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L-type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA-deficiency-induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.

11.
World J Clin Cases ; 12(16): 2876-2880, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38899287

RESUMO

BACKGROUND: Epithelioid trophoblastic tumor (ETT) is an extremely rare malignant gestational trophoblastic neoplasm commonly presenting with abnormal vaginal bleeding, abdominal pain, and increased human chorionic gonadotropin (hCG). This study reported a case of uterine ETT with the main manifestation being increased hCG. CASE SUMMARY: A 39-year-old female was referred to the Ningbo Maternal and Child Hospital of China in December 2022, complaining of increased hCG levels for 1 month. Magnetic resonance imaging revealed gestational trophoblastic tumor, and hysteroscopic electrotomy and curettage of intrauterine hyperplasia were performed. The patient was diagnosed with uterine ETT through postoperative pathological examination and immunohistochemical results. Total laparoscopic hysterectomy and bilateral salpingectomy were performed, and hCG levels returned to normal. The patient was without recurrence during the postoperative 3-month follow-up. CONCLUSION: This study reported a case of uterine ETT with the main manifestation being increased hCG, highlighting that ETT should be considered in the presence of abnormal hCG. A total laparoscopic hysterectomy is recommended.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38848117

RESUMO

Two Gram-stain-negative, straight rods, non-motile, asporogenous, catalase-negative and obligately anaerobic butyrate-producing strains, HLW78T and CYL33, were isolated from faecal samples of two healthy Taiwanese adults. Phylogenetic analyses of 16S rRNA and DNA mismatch repair protein MutL (mutL) gene sequences revealed that these two novel strains belonged to the genus Faecalibacterium. On the basis of 16S rRNA and mutL gene sequence similarities, the type strains Faecalibacterium butyricigenerans AF52-21T(98.3-98.1 % and 79.0-79.5 % similarity), Faecalibacterium duncaniae A2-165T(97.8-97.9 % and 70.9-80.1 %), Faecalibacterium hattorii APC922/41-1T(97.1-97.3 % and 80.3-80.5 %), Faecalibacterium longum CM04-06T(97.8-98.0% and 78.3 %) and Faecalibacterium prausnitzii ATCC 27768T(97.3-97.4 % and 82.7-82.9 %) were the closest neighbours to the novel strains HLW78T and CYL33. Strains HLW78T and CYL33 had 99.4 % both the 16S rRNA and mutL gene sequence similarities, 97.9 % average nucleotide identity (ANI), 96.3 % average amino acid identity (AAI), and 80.5 % digital DNA-DNA hybridization (dDDH) values, indicating that these two strains are members of the same species. Phylogenomic tree analysis indicated that strains HLW78T and CYL33 formed an independent robust cluster together with F. prausnitzii ATCC 27768T. The ANI, AAI and dDDH values between strain HLW78T and its closest neighbours were below the species delineation thresholds of 77.6-85.1 %, 71.4-85.2 % and 28.3-30.9 %, respectively. The two novel strains could be differentiated from the type strains of their closest Faecalibacterium species based on their cellular fatty acid compositions, which contained C18 : 1 ω7c and lacked C15 : 0 and C17 : 1 ω6c, respectively. Phenotypic, chemotaxonomic and genotypic test results demonstrated that the two novel strains HLW78T and CYL33 represented a single, novel species within the genus Faecalibacterium, for which the name Faecalibacterium taiwanense sp. nov. is proposed. The type strain is HLW78T (=BCRC 81397T=NBRC 116372T).


Assuntos
Técnicas de Tipagem Bacteriana , DNA Bacteriano , Faecalibacterium , Ácidos Graxos , Fezes , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Fezes/microbiologia , Humanos , RNA Ribossômico 16S/genética , Taiwan , DNA Bacteriano/genética , Ácidos Graxos/análise , Adulto , Faecalibacterium/genética , Faecalibacterium/isolamento & purificação , Faecalibacterium/classificação , Composição de Bases , Proteínas MutL/genética
13.
Gynecol Endocrinol ; 40(1): 2358227, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38807420

RESUMO

OBJECTIVE: The aim of this study was to explore the impact of growth hormone (GH) therapy on the onset and progression of puberty in girls with idiopathic short stature. METHODS: This study included 541 girls aged between 4.5 and 10.6 years who were receiving GH treatment, monitored over a 22-year follow-up period. Of these, 126 girls have been followed up to the onset of menarche. The participants were divided into two groups: a ISS control group (n = 66) and a group receiving daily GH treatment at a dose of 0.15 iu/kg (n = 60). We assessed the pubertal development and GH usage of these girls every three months. RESULTS: (1) There was no significant difference in the onset of puberty between the growth hormone (GH) treatment group and the control group; however, the average duration of puberty was longer in the treatment group compared to the control group. (2) During puberty, there were no significant differences in height growth between the treated and untreated groups. (3) The duration of GH treatment showed a significant negative correlation with the age at onset of gonadal development and the age at menarche in females within the treatment group. CONCLUSION: GH treatment does not seem to accelerate the onset of puberty but may extend its duration, without significantly impacting height growth during puberty. Additionally, longer GH treatment duration is linked to earlier gonadal development and menarche in females.


Assuntos
Estatura , Transtornos do Crescimento , Hormônio do Crescimento Humano , Menarca , Puberdade , Humanos , Feminino , Criança , Hormônio do Crescimento Humano/uso terapêutico , Hormônio do Crescimento Humano/administração & dosagem , Puberdade/efeitos dos fármacos , Transtornos do Crescimento/tratamento farmacológico , Menarca/efeitos dos fármacos , Estatura/efeitos dos fármacos , Pré-Escolar , Seguimentos , Adolescente
14.
J Immunol ; 212(11): 1609-1620, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38768409

RESUMO

In individuals diagnosed with AIDS, the primary method of sustained suppression of HIV-1 replication is antiretroviral therapy, which systematically increases CD4+ T cell levels and restores immune function. However, there is still a subset of 10-40% of people living with HIV who not only fail to reach normal CD4+ T cell counts but also experience severe immune dysfunction. These individuals are referred to as immunological nonresponders (INRs). INRs have a higher susceptibility to opportunistic infections and non-AIDS-related illnesses, resulting in increased morbidity and mortality rates. Therefore, it is crucial to gain new insights into the primary mechanisms of immune reconstitution failure to enable early and effective treatment for individuals at risk. This review provides an overview of the dynamics of key lymphocyte subpopulations, the main molecular mechanisms of INRs, clinical diagnosis, and intervention strategies during immune reconstitution failure, primarily from a multiomics perspective.


Assuntos
Infecções por HIV , HIV-1 , Reconstituição Imune , Humanos , HIV-1/imunologia , Infecções por HIV/imunologia , Infecções por HIV/tratamento farmacológico , Reconstituição Imune/imunologia , Subpopulações de Linfócitos/imunologia , Linfócitos T CD4-Positivos/imunologia
15.
BMC Vet Res ; 20(1): 204, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38755662

RESUMO

Actinobacillus pleuropneumoniae (APP) causes porcine pleuropneumonia (PCP), which is clinically characterized by acute hemorrhagic, necrotizing pneumonia, and chronic fibrinous pneumonia. Although many measures have been taken to prevent the disease, prevention and control of the disease are becoming increasingly difficult due to the abundance of APP sera, weak vaccine cross-protection, and increasing antibiotic resistance in APP. Therefore, there is an urgent need to develop novel drugs against APP infection to prevent the spread of APP. Naringin (NAR) has been reported to have an excellent therapeutic effect on pulmonary diseases, but its therapeutic effect on lung injury caused by APP is not apparent. Our research has shown that NAR was able to alleviate APP-induced weight loss and quantity of food taken and reduce the number of WBCs and NEs in peripheral blood in mice; pathological tissue sections showed that NAR was able to prevent and control APP-induced pathological lung injury effectively; based on the establishment of an in vivo/in vitro model of APP inflammation, it was found that NAR was able to play an anti-inflammatory role through inhibiting the MAPK/NF-κB signaling pathway and exerting anti-inflammatory effects; additionally, NAR activating the Nrf2 signalling pathway, increasing the secretion of antioxidant enzymes Nqo1, CAT, and SOD1, inhibiting the secretion of oxidative damage factors NOS2 and COX2, and enhancing the antioxidant stress ability, thus playing an antioxidant role. In summary, NAR can relieve severe lung injury caused by APP by reducing excessive inflammatory response and improving antioxidant capacity.


Assuntos
Infecções por Actinobacillus , Actinobacillus pleuropneumoniae , Lesão Pulmonar Aguda , Flavanonas , Proteína 1 Associada a ECH Semelhante a Kelch , Fator 2 Relacionado a NF-E2 , NF-kappa B , Animais , Camundongos , Infecções por Actinobacillus/veterinária , Infecções por Actinobacillus/tratamento farmacológico , Actinobacillus pleuropneumoniae/efeitos dos fármacos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/prevenção & controle , Flavanonas/uso terapêutico , Flavanonas/farmacologia , Heme Oxigenase-1 , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteínas de Membrana , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
Front Neurosci ; 18: 1231883, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38533447

RESUMO

Objective: Subthreshold depression (StD)/subsyndromal depression refers to a threatening precursor to depression. Aerobic exercise is a promising self-supportive adjunctive intervention and an effective measure for StD. Our study utilizes regional homogeneity (ReHo) to investigate the impact of aerobic exercise on resting-state brain function. Methods: A total of 78 subjects, aged between 18 and 48 years, (StD group, n = 44; healthy control (HC) group, n = 34) engaged in moderate-intensity aerobic exercise 3-4 times per week for 8 weeks. Resting-state brain function and structural images were acquired before and after the exercise intervention. The ReHo method was employed to analyze abnormal changes in regional brain function, and a correlation analysis was performed using the Patient Health Questionnaire-9 (PHQ-9) and Self-Rating Anxiety Scale (SAS) scores. Results: The principal observation reveals synchronous abnormalities in the right anterior cingulate gyrus of the brain in StD subjects compared to HCs at baseline, with these differences dissipating after the implementation of aerobic exercise. After completing the aerobic exercise program, the StD group exhibited a difference in the right middle cingulate gyrus, while the left supplementary motor area (SMA) was altered in the HC group. Conclusion: Disparities in neural synchronization are evident between HCs and StD subjects, and the implementation of aerobic exercise intervention can effectively mitigate these distinctions, leading to a significant reduction in depressive symptoms among StD subjects. The primary mechanism of StD symptoms may involve the inhibition of the anterior cingulate gyrus, while the effects of aerobic exercise may be related to the modulation of neural synchronization of emotional reflexes. The discovery of these fMRI evidence findings may offer novel strategies for early detection and intervention in cases of StD.

17.
J Fungi (Basel) ; 10(3)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38535188

RESUMO

Root rot as a result of Salvia miltiorrhiza is a common root disease caused by Fusarium spp., which has become one of the main diseases affecting the production of S. miltiorrhiza. Currently, several hypovirulence-related mycoviruses have been identified in many phytopathogenic fungi, including Fusarium spp., which show potential as biological controls. In this study, we report a new mycovirus, Fusarium oxysporum partitivirus 1 (FoPV1), isolated from F. oxysporum strain FCR51, which is a causal agent of S. miltiorrhiza dry rot. The FoPV1 genome contains two double-stranded RNA segments (dsRNA1 and dsRNA2). The size of dsRNA1 is 1773 bp, and it encodes a putative RNA-dependent RNA polymerase (RdRp). The dsRNA2 is 1570 bp in length, encoding a putative capsid protein (CP). Multiple sequence alignments and phylogenetic analyses based on the amino acid sequences of the RdRp and the CP proteins indicated that FoPV1 appears to be a new member of the family Partitiviridae that is related to members of the genus Gammapartitivirus. Pathogenicity assay showed that FoPV1 confers hypervirulence to its host, F. oxysporum. This is the first report of a partitivirus infecting F. oxysporum and the first hypovirulence-related mycovirus from the causal agent of S. miltiorrhiza dry rot.

18.
J Affect Disord ; 354: 323-330, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38494138

RESUMO

BACKGROUND: Arthritis is relatively common among middle-aged and older people and is a significant public health problem. However, research on the relationship between arthritis and mental health in older populations is currently limited. METHODS: Data were obtained from the Chinese Longitudinal Healthy Longevity Survey. The 10-item Center for Epidemiologic Studies Depression Scale and 7-item Generalized Anxiety Disorder Scale were used to evaluate depressive and anxiety symptoms. Arthritis status was self-reported. Linear and logistic regression analyses were conducted to assess the impact of arthritis on depression, anxiety, and comorbid depression/anxiety symptoms. RESULTS: A total of 11,104 participants aged ≥65 years (mean age, 83.1 ± 11.1 years) were included in the analysis. We detected positive associations of arthritis with depression symptoms (adjusted odds ratio [OR]: 1.57, 95 % confidence interval [CI] 1.33 to 1.86), anxiety symptoms (adjusted OR: 1.48, 95 % CI: 1.15 to 1.90), and comorbid depression/anxiety symptoms (adjusted OR: 1.88, 95 % CI: 1.41 to 2.5) in the older adult population. Participants with arthritis had higher anxiety (adjusted linear regression coefficient: 0.43, 95 % CI: 0.24 to 0.63) and depression (adjusted linear regression coefficient: 0.87, 95 % CI: 0.57 to 1.14) scores compared with those without arthritis. In addition, there were no significant interaction effects between arthritis and participant characteristics on depression symptoms, anxiety symptoms, or comorbid depression/anxiety symptoms. CONCLUSIONS: Arthritis was positively associated with depression symptoms, anxiety symptoms, and comorbid depression/anxiety symptoms among older adults. Further cohort studies are needed to validate these associations.


Assuntos
Artrite , Depressão , Pessoa de Meia-Idade , Humanos , Idoso , Idoso de 80 Anos ou mais , Depressão/epidemiologia , Depressão/complicações , Estudos Transversais , Autorrelato , Ansiedade/epidemiologia , Ansiedade/complicações , Artrite/epidemiologia , China/epidemiologia
19.
Heliyon ; 10(4): e26198, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38404781

RESUMO

Characterized by severe deficits in communication, most individuals with autism spectrum conditions (ASC) experience significant language dysfunctions, thereby impacting their overall quality of life. Wernicke's area, a classical and traditional brain region associated with language processing, plays a substantial role in the manifestation of language impairments. The current study carried out a mega-analysis to attain a comprehensive understanding of the neural mechanisms underpinning ASC, particularly in the context of language processing. The study employed the Autism Brain Image Data Exchange (ABIDE) dataset, which encompasses data from 443 typically developing (TD) individuals and 362 individuals with ASC. The objective was to detect abnormal functional connectivity (FC) between Wernicke's area and other language-related functional regions, and identify frequency-specific altered FC using Wernicke's area as the seed region in ASC. The findings revealed that increased FC in individuals with ASC has frequency-specific characteristics. Further, in the conventional frequency band (0.01-0.08 Hz), individuals with ASC exhibited increased FC between Wernicke's area and the right thalamus compared with TD individuals. In the slow-5 frequency band (0.01-0.027 Hz), increased FC values were observed in the left cerebellum Crus II and the right lenticular nucleus, pallidum. These results provide novel insights into the potential neural mechanisms underlying communication deficits in ASC from the perspective of language impairments.

20.
Front Neurol ; 15: 1298477, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38356887

RESUMO

Objective: This study aimed to develop an arbitrary-dimensional nerve root reconstruction magnetic resonance imaging (ANRR-MRI) technique for identifying the leakage orificium of sacral meningeal cysts (SMCs) without spinal nerve root fibres (SNRFs). Methods: This prospective study enrolled 40 consecutive patients with SMCs without SNRFs between March 2021 and March 2022. Magnetic resonance neural reconstruction sequences were performed for preoperative evaluation. The cyst and the cyst-dura intersection planes were initially identified based on the original thin-slice axial T2-weighted images. Sagittal and coronal images were then reconstructed by setting each intersecting plane as the centre. Then, three-dimensional reconstruction was performed, focusing on the suspected leakage point of the cyst. Based on the identified leakage location and size of the SMC, individual surgical plans were formulated. Results: This cohort included 30 females and 10 males, with an average age of 42.6 ± 12.2 years (range, 17-66 years). The leakage orificium was located at the rostral pole of the cyst in 23 patients, at the body region of the cyst in 12 patients, and at the caudal pole in 5 patients. The maximum diameter of the cysts ranged from 2 cm to 11 cm (average, 5.2 ± 1.9 cm). The leakage orificium was clearly identified in all patients and was ligated microscopically through a 4 cm minimally invasive incision. Postoperative imaging showed that the cysts had disappeared. Conclusion: ANRR-MRI is an accurate and efficient approach for identifying leakage orificium, facilitating the precise diagnosis and surgical treatment of SMCs without SNRFs.

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