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1.
Braz. j. biol ; 84: e250821, 2024. tab
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1345541

RESUMO

Abstract The present study aimed to determine the effect of different levels of protein on the growth, body composition, amino acid profile and serology of Channa marulius fingerlings. The experiment was conducted in ten happas installed in earthen ponds, each stocked with 10 fishes for 90 days. Four commercial fish feeds having 25%, 30%, 32% and 40% crude protein (CP) levels were fed to fish at 3% of their wet body weight three times a day. The results of the study revealed that highest weight gain, feed conversion ratio and survival rate were observed in 30% protein feed. Meanwhile, moisture content was higher in fish fed with 30% CP feed while highest crude protein was recorded in 40% CP fed fish. Lowest fat content was observed in 32% CP feed. Amino acid profile of fish revealed better results in 30% CP feed. Total protein, glucose and globulin were also highest in fish feeding 30% CP feed, while albumin was highest in 40% CP feed. It is concluded that 30% CP feed showed better results in terms of growth, amino acid profile and serological parameters without effecting fish body composition.


Resumo O presente estudo teve como objetivo determinar o efeito de diferentes níveis de proteína sobre o crescimento, composição corporal, perfil de aminoácidos e sorologia de alevinos de Channa marulius. O experimento foi conduzido em dez happas instalados em tanques de terra, cada um abastecido com 10 peixes, por 90 dias. Quatro alimentos para peixes comerciais com níveis de 25%, 30%, 32% e 40% de proteína bruta (PB) foram dados aos peixes com 3% de seu peso corporal úmido três vezes ao dia. Os resultados do estudo revelaram que maior ganho de peso, taxa de conversão alimentar e taxa de sobrevivência foram observados em 30% de proteína alimentar. Enquanto isso, o conteúdo de umidade foi maior em peixes alimentados com 30% de PB, enquanto a proteína bruta mais alta foi registrada em peixes alimentados com 40% de PB. O menor conteúdo de gordura foi observado em rações com 32% de PB. O perfil de aminoácidos dos peixes revelou melhores resultados na ração com 30% de PB. Proteína total, glicose e globulina também foram maiores em peixes alimentados com ração com 30% de PB, enquanto a albumina foi mais alta com 40% de PB. Conclui-se que a ração com 30% de PB apresentou melhores resultados em termos de crescimento, perfil de aminoácidos e parâmetros sorológicos sem afetar a composição corporal dos peixes.


Assuntos
Animais , Peixes , Ração Animal/análise , Paquistão , Composição Corporal , Lagoas , Dieta
2.
Braz. j. biol ; 84: e253613, 2024. tab
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1345548

RESUMO

Abstract Soybean meal is an inexpensive plant origin protein which has been used in practical diets as a replacement of animal protein such as fish meal or chicken meal, due to the uneconomical price of animal protein diets. Consequently, a research study was conducted on some commercial species of Indian major carps i.e. Catla (Cattla cattla), Rohu (Labeo rohita) and Mrigala (Cirhinus mrigala) (Hamilton, 1822) to estimate optimum dietary protein requirement of soy bean meal in diet in an intensive polyculture. Three different diets (SBM I, SBM II and SBM III) were formulated by 80%, 50% and 20% replacement of fish meal with soybean meal from a 45% fish meal diet (control).Highest monthly mean weight gain was obtained by SBM II (with 35% CP and about 50% substitution of fish meal), while SBM III (45% Crude Protein and about 20% substitution of fish meal) was stood second. All tested diets respond enormously by producing high yield as compare to control diet, though SBM II generated highest yield among all. On the bases of the following research, it was revealed that the SBM can surrogate even50% fish meal without any augmentation of other amino acids in the diet of Indian major carps.


Resumo O farelo de soja é uma proteína de origem vegetal de baixo custo que tem sido usada em dietas práticas como um substituto da proteína animal, como farinha de peixe ou farinha de frango, devido ao preço não econômico das dietas com proteína animal. Consequentemente, um estudo/pesquisa foi realizado com algumas espécies comerciais de carpas principais indianas, ou seja, Catla (Cattla cattla), Rohu (Labeo rohita) e Mrigala (Cirhinus mrigala) (Hamilton, 1822), para estimar a necessidade ideal de proteína dietética de farelo de soja na dieta em uma policultura intensiva. Três dietas diferentes (SBM I, SBM II e SBM III) foram formuladas por 80%, 50% e 20% de substituição de farinha de peixe por farelo de soja de uma dieta de 45% de farinha de peixe (controle). O maior ganho de peso médio mensal foi obtido por SBM II (com 35% PB e cerca de 50% de substituição de farinha de peixe), enquanto SBM III (45% de proteína bruta e cerca de 20% de substituição de farinha de peixe) ficou em segundo lugar. Todas as dietas testadas respondem enormemente produzindo alto rendimento em comparação com a dieta controle, embora SBM II tenha gerado o maior rendimento entre todas. Com base na pesquisa a seguir, foi revelado que o SBM pode substituir até 50% da farinha de peixe sem qualquer aumento de outros aminoácidos na dieta das carpas principais indianas.


Assuntos
Animais , Carpas , Cyprinidae , Soja , Alimentos Marinhos , Dieta/veterinária , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal
3.
Braz. j. biol ; 84: e256732, 2024. tab, graf, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1364524

RESUMO

Germin-like proteins (GLPs) play an important role against various stresses. Vitis vinifera L. genome contains 7 GLPs; many of them are functionally unexplored. However, the computational analysis may provide important new insight into their function. Currently, physicochemical properties, subcellular localization, domain architectures, 3D structures, N-glycosylation & phosphorylation sites, and phylogeney of the VvGLPs were investigated using the latest computational tools. Their functions were predicted using the Search tool for the retrieval of interacting genes/proteins (STRING) and Blast2Go servers. Most of the VvGLPs were extracellular (43%) in nature but also showed periplasmic (29%), plasma membrane (14%), and mitochondrial- or chloroplast-specific (14%) expression. The functional analysis predicted unique enzymatic activities for these proteins including terpene synthase, isoprenoid synthase, lipoxygenase, phosphate permease, receptor kinase, and hydrolases generally mediated by Mn+ cation. VvGLPs showed similarity in the overall structure, shape, and position of the cupin domain. Functionally, VvGLPs control and regulate the production of secondary metabolites to cope with various stresses. Phylogenetically VvGLP1, -3, -4, -5, and VvGLP7 showed greater similarity due to duplication while VvGLP2 and VvGLP6 revealed a distant relationship. Promoter analysis revealed the presence of diverse cis-regulatory elements among which CAAT box, MYB, MYC, unnamed-4 were common to all of them. The analysis will help to utilize VvGLPs and their promoters in future food programs by developing resistant cultivars against various biotic (Erysiphe necator and in Powdery Mildew etc.) and abiotic (Salt, drought, heat, dehydration, etc.) stresses.


As proteínas do tipo germin (GLPs) desempenham um papel importante contra vários estresses. O genoma de Vitis vinifera L. contém 7 GLPs; muitos deles são funcionalmente inexplorados. No entanto, a análise computacional pode fornecer informações importantes sobre sua função. Atualmente, as propriedades físico-químicas, localização subcelular, arquitetura de domínio, estruturas 3D, sítios de N-glicosilação e fosforilação e estudos filogenéticos dos VvGLPs foram conduzidos usando as ferramentas computacionais mais recentes. Suas funções foram previstas usando a ferramenta Search para recuperação de genes/proteínas em interação (STRING) e servidores Blast2Go. A maioria dos VvGLPs são extracelulares (43%) na natureza, mas também mostraram expressão periplasmática (29%), na membrana plasmática (14%) e específica para mitocôndrias ou cloroplastos (14%). A análise funcional previu atividades enzimáticas únicas para essas proteínas, incluindo terpeno sintase, isoprenoide sintase, lipoxigenase, fosfato permease, receptor quinase e hidrolases geralmente mediadas por cátion Mn +. VvGLPs mostraram similaridade na estrutura geral, forma e posição do domínio cupin. Funcionalmente, os VvGLPs controlam e regulam a produção de metabólitos secundários para lidar com vários estresses. Filogeneticamente, VvGLP1, -3, -4, -5 e VvGLP7 mostraram maior similaridade devido à duplicação, enquanto VvGLP2 e VvGLP6 revelaram uma relação distante. A análise do promotor revelou a presença de diversos elementos cis-reguladores, entre os quais CAAT box, MYB, MYC, sem nome-4, sendo comum a todos eles. A análise ajudará a utilizar VvGLPs e seus promotores em programas alimentares futuros, desenvolvendo cultivares resistentes contra vários estresses bióticos (Erysiphe necator e no oídio, etc.) e abióticos (sal, seca, calor, estresse hídrico, etc.).


Assuntos
Estresse Fisiológico/genética , Proteínas , Vitis/genética
4.
Braz. j. biol ; 84: e254646, 2024. tab, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1360224

RESUMO

Chronic stress (CS) can contribute to dysfunction in several organs including liver and kidney. This study was performed to investigate the changes in serum biochemistry, histological structure, as well as in localization of tyrosine phosphorylated proteins (TyrPho) and Heat shock protein 70 (Hsp-70) in liver and kidney tissues of CS rats induced by two stressors (restrained and force swimming) for 60 consecutive days. Samples of blood, liver, and kidney were collected from adult male Sprague-Dawley rats in each group. Our results showed that serum biochemical parameters including corticosterone, blood sugar, urea nitrogen, creatinine, cholesterol, triglyceride, HDL-C, LDL-C, ALT, AST, alkaline phosphatase in CS group were significantly different from that in normal group in both liver and kidney tissues. Although histological structure was not changed. TyrPho expression was significantly increased in liver lysate but significantly decreased in kidney. Hsp-70 expression in liver increased whereas in kidney decreased. In conclusion, CS can induce changes in liver and kidney functions.


O estresse crônico (SC) pode contribuir para a disfunção em vários órgãos, incluindo fígado e rim. Este estudo foi realizado para investigar as alterações na bioquímica sérica, estrutura histológica, bem como na localização de proteínas tirosina fosforiladas (TyrPho) e proteína de choque térmico 70 (Hsp-70) em tecidos hepáticos e renais de ratos CS induzidas por dois estressores (restrito e natação forçada) por 60 dias consecutivos. Amostras de sangue, fígado e rim foram coletadas de ratos Sprague-Dawley machos adultos em cada grupo. Nossos resultados mostraram que os parâmetros bioquímicos séricos, incluindo corticosterona, glicemia, nitrogênio ureico, creatinina, colesterol, triglicerídeos, HDL-C, LDL-C, ALT, AST, fosfatase alcalina no grupo CS foram significativamente diferentes do grupo normal em ambos os fígados e tecidos renais. Embora a estrutura histológica não tenha sido alterada, a expressão de TyrPho aumentou significativamente no lisado hepático, mas diminuiu significativamente no rim. A expressão de Hsp-70 no fígado aumentou, enquanto que no rim diminuiu. Em conclusão, a CS pode induzir alterações nas funções hepáticas e renais.


Assuntos
Ratos , Estresse Fisiológico , Ratos Sprague-Dawley , Rim/anatomia & histologia , Fígado/anatomia & histologia
5.
BMC Neurosci ; 24(1): 10, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36721107

RESUMO

BACKGROUND: Glioblastoma (GBM) is the most common malignant intracranial tumor with a low survival rate. However, only few drugs responsible for GBM therpies, hence new drug development for it is highly required. The natural product Cudraflavone B (CUB) has been reported to potentially kill a variety of tumor cells. Currently, its anit-cancer effect on GBM still remains unknown. Herein, we investigated whether CUB could affect the proliferation and apoptosis of GBM cells to show anti-GBM potential. RESULTS: CUB selectively inhibited cell viability and induced cell apoptosis by activating the endoplasmic reticulum stress (ER stress) related pathway, as well as harnessing the autophagy-related PI3K/mTOR/LC3B signaling pathway. Typical morphological changes of autophagy were also observed in CUB treated cells by microscope and scanning electron microscope (SEM) examination. 4-Phenylbutyric acid (4-PBA), an ER stress inhibitor, restored the CUB-caused alteration in signaling pathway and morphological change. CONCLUSIONS: Our finding suggests that CUB impaired cell growth and induced cell apoptosis of glioblastoma through ER stress and autophagy-related signaling pathways, and it might be an attractive drug for treatment of GBM.

6.
BMC Vet Res ; 19(1): 28, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36721143

RESUMO

BACKGROUND: Bovine herpes virus (BoHV 1 and BoHV-5) are the causative agents of infectious bovine rhinotracheitis (IBR). IBR is responsible for important economic losses in the cattle industry. The envelope glycoprotein B (gB) is essential for BoHV infection of cattle's upper respiratory and genital tract. gB is one of the main candidate antigens for a potential recombinant vaccine since it induces a strong and persistent immune response. RESULTS: In this study, gB of BoHV-1 and BoHV-5 was characterized in terms of function, structure, and antigenicity through bioinformatics tools. gB showed conserved sequence and structure, so, both domains named PH Like 1 and 2 domains of each virus were selected for the design of a bivalent vaccine candidate. The immunoinformatic study showed that these two domains have epitopes recognizable by B and T lymphocytes, followed by this, the cDNA domains from BoHV-1/5 gB (Domains-gB) were transformed into the yeast Komagataella phaffii GS115 (previously known as Pichia pastoris). A recombinant protein with molecular weight of about 110 kDa was obtained from the culture media. The vaccine candidate protein (Domains-gB) was recognized by a monoclonal antibody from a commercial ELISA kit used for IBR diagnostic, which may suggest that the epitopes are conserved of the entire infectious virus. CONCLUSION: Overall, it was shown that the recombinant domains of BoHV-1/5 gB have antigenic and immunogenic properties similar to the native gB. This vaccine candidate is promising to be used in future studies to assess its immunogenicity in an animal model.

7.
Respir Res ; 24(1): 37, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36721187

RESUMO

BACKGROUND: Our previous studies have suggested that bromodomain protein 4 (BRD4) is increased in the lung of stable chronic obstructive pulmonary disease (COPD) patients, which has been shown to be involved in inflammatory responses. We investigated its role in the viral exacerbation of COPD. METHODS: BRD4, interleukin (IL)-6 and IL-8 were measured in the blood and sputum of stable COPD patients and patients with viral exacerbation. Mice were exposed to cigarette smoke (CS) and/or infected with influenza virus as an in vivo model. BRD4, IL-6 and keratinocyte-derived chemokine (KC) were measured in the lung. BEAS-2B cells were treated with CS extract and/or influenza virus as an in vitro model. BRD4, IL-6 and IL-8 were measured in the cells and/or culture supernatant. RESULTS: BRD4 was increased in COPD patients with viral exacerbation compared with those in stable condition and its expression was correlated with IL-6 and IL-8 expression. Inflammatory cells, IL-6, KC and BRD4 were synergistically induced in the lung of mice by viral infection and CS exposure, and the former three were decreased by JQ1 (BRD4 inhibitor) treatment. IL-6, IL-8 and BRD4 were significantly induced by CS extract and influenza virus in bronchial epithelial cells, and this upregulation was suppressed by knockdown of BRD4 expression. CONCLUSIONS: Our findings indicate that CS and viruses may synergistically induce IL-6 and IL-8 expression through their synergistic induction of BRD4 expression, which might contribute to the enhanced inflammatory response in the viral exacerbation of COPD.

8.
Fluids Barriers CNS ; 20(1): 8, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36721242

RESUMO

BACKGROUND: The multidrug resistance (MDR) transporters, P-glycoprotein (P-gp, encoded by ABCB1) and breast cancer resistance protein (BCRP/ABCG2) contribute to the blood-brain barrier (BBB), protecting the brain from drug exposure. The impact of infection on MDR in the developing human BBB remains to be determined. We hypothesized that exposure to bacterial and viral pathogen-associated molecular patterns (PAMPs) modify MDR expression and activity in human fetal brain endothelial cells (hfBECs) isolated from early and mid-gestation brain microvessels. METHODS: We modelled infection (4 h and 24 h) using the bacterial PAMP, lipopolysaccharide (LPS; a toll-like receptor [TLR]-4 ligand) or the viral PAMPs, polyinosinic polycytidylic acid (Poly I:C; TLR-3 ligand) and single-stranded RNA (ssRNA; TLR-7/8 ligand). mRNA expression was assessed by qPCR, whereas protein expression was assessed by Western blot or immunofluorescence. P-gp and BCRP activity was evaluated by Calcein-AM and Chlorin-6 assays. RESULTS: TLRs-3,4 and 8 were expressed by the isolated hfBECs. Infection mimics induced specific pro-inflammatory responses as well as changes in P-gp/ABCB1 or BCRP/ABCG2 expression (P < 0.05). LPS and ssRNA significantly decreased P-gp activity at 4 and 24 h in early and mid-gestation (P < 0.03-P < 0.001), but significantly increased BCRP activity in hfBECs in a dose-dependent pattern (P < 0.05-P < 0.002). In contrast, Poly-IC significantly decreased P-gp activity after 4 h in early (P < 0.01) and mid gestation (P < 0.04), but not 24 h, and had no overall effect on BCRP activity, though BCRP activity was increased with the highest dose at 24 h in mid-gestation (P < 0.05). CONCLUSIONS: Infectious PAMPs significantly modify the expression and function of MDR transporters in hfBECs, though effects are PAMP-, time- and dose-specific. In conclusion, bacterial and viral infections during pregnancy likely have profound effects on exposure of the fetal brain to physiological and pharmacological substrates of P-gp and BCRP, potentially leading to altered trajectories of fetal brain development.

9.
Microbiome ; 11(1): 18, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36721246

RESUMO

BACKGROUND: Narrow host range is a major limitation for phage applications, but phages can evolve expanded host range through adaptations in the receptor-binding proteins. RESULTS: Here, we report that Pseudomonas phage K8 can evolve broader host range and higher killing efficiency at the cost of virion stability. Phage K8 host range mutant K8-T239A carries a mutant version of the putative baseplate wedge protein GP075, termed GP075m. While phage K8 adsorbs to hosts via the O-specific antigen of bacterial LPS, phage K8-T239A uses GP075m to also bind the bacterial core oligosaccharide, enabling infection of bacterial strains resistant to K8 infection due to modified O-specific antigens. This mutation in GP075 also alters inter-protein interactions among phage proteins, and reduces the stability of phage particles to environmental stressors like heat, acidity, and alkalinity. We find that a variety of mutations in gp075 are widespread in K8 populations, and that the gp075-like genes are widely distributed among the domains of life. CONCLUSION: Our data show that a typical life history tradeoff occurs between the stability and the host range in the evolution of phage K8. Reservoirs of viral gene variants may be widely present in phage communities, allowing phages to rapidly adapt to any emerging environmental stressors. Video Abstract.

10.
Protein Sci ; : e4586, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36721353

RESUMO

In addition to their membrane-bound chlorophyll a/c light-harvesting antenna, the cryptophyte algae have evolved a unique phycobiliprotein antenna system located in the thylakoid lumen. The basic unit of this antenna consists of two copies of an αß protomer where the α and ß subunits scaffold different combinations of a limited number of linear tetrapyrrole chromophores. While the ß subunit is highly conserved, encoded by a single plastid gene, the nuclear-encoded α subunits have evolved diversified multigene families. It is still unclear how this sequence diversity results in the spectral diversity of the mature proteins. By careful examination of three newly-determined crystal structures in comparison with three previously obtained, we show how the α subunit amino acid sequences control chromophore conformations and hence spectral properties even when the chromophores are identical. Previously we have shown that α subunits control the quaternary structure of the mature αß.αß complex (either open or closed), however, each species appeared to only harbor a single quaternary form. Here we show that species of the Hemiselmis genus contain expressed α subunit genes that encode both distinct quaternary structures. Finally, we have discovered a common single-copy gene (expressed into protein) consisting of tandem copies of a small α subunit that could potentially scaffold pairs of light harvesting units. Together, our results show how the diversity of the multigene α subunit family produces a range of mature cryptophyte antenna proteins with differing spectral properties, and the potential for minor forms that could contribute to acclimation to varying light regimes. This article is protected by copyright. All rights reserved.

11.
Infect Drug Resist ; 16: 477-486, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36721632

RESUMO

Background: Periprosthetic joint infection (PJI) is a catastrophic complication after total joint arthroplasty (TJA). Timely and accurate diagnosis is important for the management of PJI. Currently, many biomarkers are available for the diagnosis of PJI, but which inflammatory biomarker combination has the best diagnostic value has not been reported. Materials and Methods: We retrospectively analyzed 244 patients who underwent revision knee or hip arthroplasty in our institution. They were divided into two groups: 87 in the PJI group and 157 in the aseptic failure (AF) group. The preoperative C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), CRP-to-albumin ratio (CAR), CRP-to-lymphocyte ratio (CLR), neutrophil-to-albumin ratio (NAR) and platelet-to-albumin ratio (PAR) were determined and compared between the two groups. Receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to assess the diagnostic value of all biomarkers, and the optimal cut-off value, positive predictive value (PPV) and negative predictive value (NPV) were further calculated by the Youden index. Results: The NLR, PLR, CAR, CLR, NAR and PAR of the PJI group were significantly higher than those of the AF group (P<0.001). According to the ROC and AUC results, the diagnostic value of CAR and CLR was considered excellent with AUCs of 0.931 and 0.935, respectively. The diagnostic value of NAR (0.739) and PAR (0.785) were fair, the diagnostic value of NLR (0.694) was poor, and PLR (0.535) had no diagnostic ability. Subgroup analysis showed no significant differences in combined inflammatory biomarkers between the two groups. Conclusion: CAR and CLR are valuable combined inflammatory biomarkers for diagnosing PJI, while other markers were of limited value for the diagnosis of PJI.

12.
Asian J Urol ; 10(1): 50-57, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36721699

RESUMO

Objective: Deleted in liver cancer 1 (DLC1) is a GTPase-activating protein that is reported as a suppressor in certain human cancers. However, the detailed biological function of DLC1 is still unclear in human prostate cancer (PCa). In the present study, we aimed to explore the function of DLC1 in PCa cells. Methods: Silencing and overexpression of DLC1 were induced in an androgen-sensitive PCa cell line (LNCaP) using RNA interference and lentiviral vector transduction. The Cell Counting Kit-8 assay was performed to determine cell proliferation. The cell cycle was examined by performing a propidium iodide staining assay. Results: Our results indicated that DLC1 overexpression markedly suppressed the proliferation and cell cycle progression of LNCaP cells. Moreover, DLC1 expression was negatively correlated with Rho-associated protein kinase (ROCK) expression in LNCaP cells. Importantly, this study showed that the ROCK inhibitor Y27632 restored the function of DLC1 in LNCaP cells and reduced the tumorigenicity of LNCaP cells in vivo. Conclusion: Our results indicated that DLC1 overexpression markedly suppressed the proliferation and cell cycle progression of PCa cells and negatively correlated with ROCK expression in PCa cells and tissue.

13.
J Orthop Translat ; 39: 43-54, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36721767

RESUMO

Objective: To investigate the therapeutic effects of static magnetic field (SMF) and its regulatory mechanism in the repair of osteoarthritic cartilage. Methods: Fourteen-week-old female C57BL/6 mice were randomly divided into the sham operation group and the osteoarthritis (OA) groups with and without SMF application. SMF was applied at 200 â€‹mT for two consecutive weeks. Changes in knee cartilage were examined by histomorphometry, and the chondrogenesis and migration of endogenous stem cells were assessed. The expression of SRY-related protein 9 (SOX9), Collagen type II (COL2), matrix metallopeptidase 13 (MMP13), stromal cell-derived factor 1/C-X-C chemokine receptor type 4 (SDF-1/CXCR4), Piezo1 and other genes was evaluated, and the mechanism of SMF's action was tested using the CXCR4 inhibitor, AMD3100, and Piezo1 siRNA. Results: SMF significantly decreased the OARSI scores after induction of OA. SMF was beneficial to chondrogenesis by elevating SOX9. In the OA mouse model, an increase in MMP13 with a decrease in COL2 led to the destruction of the cartilage extracellular matrix, which was suppressed by SMF. SMF promoted the migration of cartilage-derived stem/progenitor cells and bone marrow-derived mesenchymal stem cells (MSCs). It increased SDF-1 and CXCR4, while the CXCR4 inhibitor significantly suppressed the beneficial effects of SMF. The application of Piezo1 siRNA inhibited the SMF-induced increase of CXCR4. Conclusion: SMF enhanced chondrogenesis and improved cartilage extracellular matrices. It activated the Piezo1-mediated SDF-1/CXCR4 regulatory axis and promoted the migration of endogenous stem cells. Collectively, it attenuated the pathological progression of cartilage destruction in OA mice. The Translational potential of this article: The findings in this study provided convincing evidence that SMF could enhance cartilage repair and improve OA symptoms, suggesting that SMF could have clinical value in the treatment of OA.

14.
Iran J Child Neurol ; 17(1): 99-110, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36721830

RESUMO

Objectives: Precise and early diagnosis of neonatal asphyxia may improve outcomes. Recent studies aim to identify diagnostic biomarkers in neonates at risk for brain damage. The current study was designed to evaluate the diagnostic value of new biomarkers for neonatal asphyxia. Materials & Methods: This prospective study was conducted with an available sampling of infants upper 35 weeks of gestational age, including neonates with asphyxia (case group) and healthy controls, 2014-2022, in Ghaem Hospital, Mashhad, Iran. Data collection was performed utilizing a researcher-made questionnaire, including maternal and neonatal characteristics, as well as clinical and laboratory evaluation. Serum umbilical cord levels of interleukin-6 (IL6), interleukin-1-beta (IL- 1ß), pro-oxidant-antioxidant balance (PAB), and heat shock protein-70 (HSP70), as well as nucleated red blood cells count (NRBC), were determined. Data were analyzed by t-test, Chi-square, receiver operating characteristic (ROC), and regression models. Results: The differences in variables IL6, IL1ß, PAB, NRBC/100WBC, and HSP70 were statistically significant between the two groups (in all cases, P<0.0001). In the diagnosis of asphyxia, the most sensitive marker (89%) was IL1ß more than 2.39 pg/ml and HSP 70 upper than 0.23 ng/ml, while IL6 was higher than 9pg/ml, determined as the most specific marker (85%). Furthermore, a combination of HSP + PAB and IL6 + lL1b + PAB + NRBC/100WBC possesses the prediction power of 93.2% and 87.3%, respectively, for diagnosing asphyxia. Conclusion: According to data analysis, the combination of new biochemical markers (NRBC count, IL6, IL1ß, PAB, and HSP 70) could be a reliable marker for diagnosing infants with asphyxia.

15.
Glycobiology ; 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36721988

RESUMO

Thrombospondin 1 (THBS1) is a secreted extracellular matrix glycoprotein that regulates a variety of cellular and physiological processes. THBS1's diverse functions are attributed to interactions between the modular domains of THBS1 with an array of proteins found in the extracellular matrix. THBS1's three Thrombospondin Type 1 Repeats (TSRs) domains are modified with O-linked glucose-fucose disaccharide and C-mannose. It is unknown whether these modifications impact trafficking and/or function of THBS1 in vivo. The O-fucose is added by Protein O-fucosyltransferase 2 (POFUT2) and is sequentially extended to the disaccharide by ß3glucosyltransferase (B3GLCT). The C-mannose is added by one or more of four C-mannosyltransferases. O-fucosylation by POFUT2/B3GLCT in the endoplasmic reticulum has been proposed to play a role in quality control by locking TSR domains into their 3-dimensional fold, allowing for proper secretion of many O-fucosylated substrates. Prior studies showed the siRNA knockdown of POFUT2 in HEK293T cells blocked secretion of TSRs 1-3 from THBS1. Here we demonstrated that secretion of THBS1 TSRs 1-3 was not reduced by CRISPR-Cas9-mediated knockout of POFUT2 in HEK293T cells and demonstrated that knockout of Pofut2 or B3glct in mice did not reduce trafficking of endogenous THBS1 to secretory granules of platelets, a major source of THBS1. Additionally, we demonstrated that all three TSRs from platelet THBS1 were highly C-mannosylated, which has been shown to stabilize TSRs in vitro. Combined these results suggested that POFUT2 substrates with TSRs that are also modified by C-mannose may be less susceptible to trafficking defects resulting from loss of the glucose-fucose disaccharide.

16.
Metallomics ; 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36722151

RESUMO

Copper is a highly reactive element involved in a myriad of biological reactions. Thus, while essential for mammalian cells, its concentrations must be kept in check in order to avoid toxicity. This metal participates in redox reactions and may exacerbate oxidative stress in aerobic organisms. Nonetheless, the actual driving force of copper-induced cell death is yet unknown. Likely, free copper ions may target different biomolecules which are crucial for the proper functioning of an organism. In this work, we show that free copper induces protein aggregation in serum. The wide set of proteins present in these biological samples are not equally prone to copper-induced aggregation and some, such as albumin, are highly resistant whereas γ-globulins are highly sensitive. The identity of the proteins in the aggregates becomes fairly homogeneous as metal concentrations go as low as 20 µM. The identification of the proteins by mass spectrometry indicates a preponderance of IgG and a minor presence of other different proteins. Therefore, free copper in blood may serve to the formation of circulating protein aggregates with a core of IgG. This may impact on health not only due to the activity of aggregated IgG but also due to the many proteins co-aggregated. Understanding whether the γ-globulin core and the heterogeneous subgroup of proteins elicit differential responses in the organisms requires further research.

17.
J R Soc Interface ; 20(199): 20220510, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36722169

RESUMO

Biochemical networks are at the heart of cellular information processing. These networks contain distinct facets: (i) processing of information from the environment via cascades/pathways along with network regulation and (ii) modification of substrates in different ways, to confer protein functionality, stability and processing. While many studies focus on these factors individually, how they interact and the consequences for cellular systems behaviour are poorly understood. We develop a systems framework for this purpose by examining the interplay of network regulation (canonical feedback and feed-forward circuits) and multisite modification, as an exemplar of substrate modification. Using computational, analytical and semi-analytical approaches, we reveal distinct and unexpected ways in which the substrate modification and network levels combine and the emergent behaviour arising therefrom. This has important consequences for dissecting the behaviour of specific signalling networks, tracing the origins of systems behaviour, inference of networks from data, robustness/evolvability and multi-level engineering of biomolecular networks. Overall, we repeatedly demonstrate how focusing on only one level (say network regulation) can lead to profoundly misleading conclusions about all these aspects, and reveal a number of important consequences for experimental/theoretical/data-driven interrogations of cellular signalling systems.

18.
Genetics ; 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36722258

RESUMO

The auxin-inducible degradation system has been widely adopted in the Caenorhabditis elegans research community for its ability to empirically control the spatiotemporal expression of target proteins. This system can efficiently degrade auxin-inducible degron (AID)-tagged proteins via the expression of a ligand-activatable AtTIR1 protein derived from A. thaliana that adapts target proteins to the endogenous C. elegans proteasome. While broad expression of AtTIR1 using strong, ubiquitous promoters can lead to rapid degradation of AID-tagged proteins, cell type-specific expression of AtTIR1 using spatially restricted promoters often results in less efficient target protein degradation. To circumvent this limitation, we have developed a FLP/FRT3-based system that functions to reanimate a dormant, high-powered promoter that can drive sufficient AtTIR1 expression in a cell type-specific manner. We benchmark the utility of this system by generating a number of tissue-specific FLP-ON::TIR1 drivers to reveal genetically separable cell type-specific phenotypes for several target proteins. We also demonstrate that the FLP-ON::TIR1 system is compatible with enhanced degron epitopes. Finally, we provide an expandable toolkit utilizing the basic FLP-ON::TIR1 system that can be adapted to drive optimized AtTIR1 expression in any tissue or cell type of interest.

19.
J Cell Mol Med ; 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36722323

RESUMO

XPO1 (Exportin-1) is the nuclear export protein responsible for the normal shuttling of several proteins and RNA species between the nucleocytoplasmic compartment of eukaryotic cells. XPO1 recognizes the nuclear export signal (NES) of its cargo proteins to facilitate its export. Alterations of nuclear export have been shown to play a role in oncogenesis in several types of solid tumour and haematologic cancers. Over more than a decade, there has been substantial progress in targeting nuclear export in cancer using selective XPO1 inhibitors. This has resulted in recent approval for the first-in-class drug selinexor for use in relapsed, refractory multiple myeloma and diffuse large B-cell lymphoma (DLBCL). Despite these successes, not all patients respond effectively to XPO1 inhibition and there has been lack of biomarkers for response to XPO1 inhibitors in the clinic. Using haematologic malignancy cell lines and samples from patients with myelodysplastic neoplasms treated with selinexor, we have identified XPO1, NF-κB(p65), MCL-1 and p53 protein levels as protein markers of response to XPO1 inhibitor therapy. These markers could lead to the identification of response upon XPO1 inhibition for more accurate decision-making in the personalized treatment of cancer patients undergoing treatment with selinexor.

20.
Stroke ; 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36722344

RESUMO

BACKGROUND: Insulin resistance is associated with stroke recurrence and poor functional outcomes of nondiabetic patients with ischemic stroke. The study aimed to investigate whether the association between insulin resistance and the prognosis of nondiabetic patients with ischemic stroke was mediated by systematic inflammation. METHODS: Patients with ischemic stroke but without a history of diabetes who were enrolled in CNSR-III (Third China National Stroke Registry) were included in the study and followed up for 1 year after stroke onset. Insulin resistance was determined by using the homeostasis model assessment for insulin resistance (HOMA-IR) method. hs-CRP (high-sensitivity C-reactive protein) and Lp-PLA2 (lipoprotein-associated phospholipase A2) activity were measured at baseline. The primary outcome was stroke recurrence, and other outcomes included composite vascular events, mortality, and poor functional outcome (modified Rankin Scale score, 3-6). Multivariable Cox or logistic regression analyses were performed to estimate the association between HOMA-IR and the study outcomes. A mediation analysis was performed to examine the relationship between insulin resistance and the study outcomes mediated by systemic inflammation. RESULTS: Among a total of 3808 nondiabetic patients with ischemic stroke who were included in the study, the median HOMA-IR was 1.79 (interquartile range, 1.05-2.97). After adjustments for potential confounders, higher HOMA-IR quartiles were associated with higher risks of stroke recurrence, ischemic stroke, and composite vascular events, especially in the large artery atherosclerosis subtype. hs-CRP partially mediated the association between the HOMA-IR index and the prognosis of ischemic stroke (mediation proportion, 5.9% for stroke recurrence and 7.5% for composite vascular events). No evidence of Lp-PLA2 activity mediating the association of insulin resistance with stroke outcomes was observed. CONCLUSIONS: Our study found that insulin resistance was associated with poor clinical outcomes in nondiabetic patients with ischemic stroke, which was partially mediated by hs-CRP with a modest amount.

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