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1.
Biochem Biophys Res Commun ; 525(3): 706-713, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32139124

RESUMO

GGNBP1 is known as gametogenetin protein 1 (GGN1)-interacting protein. It is specifically expressed in the mitochondria of the testis, while its functional role during spermatogenesis is still unknown. Here, we showed that the disruption of Ggnbp1 resulted in abnormal spermiogenesis in around 40% mice, while the others show no defects in the genital system. Moreover, upon treatment with low dose of bisphenol A (BPA), Ggnbp1 knockout mice were more sensitive to environmental pollutant than control mice. The treatment led to decrease in sperm motility and production of abnormal spermatozoa. These results suggest that GGNBP1 mainly ensures proper spermiogenesis in response to various stresses in male mice.

2.
Autophagy ; 16(1): 18-27, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31203720

RESUMO

Sexual reproduction is the most common form of reproduction among eukaryotes, which is characterized by a series of massive cellular or tissue renovations. Recent studies have revealed novel functions of autophagy during sexual reproductive processes, ranging from yeast to mammals. In mammals, autophagy is indispensable for spermatogenesis and oogenesis, and it participates in early embryonic development and maternal-fetus crosstalk to ensure the development of embryos or fetuses. Thus, autophagy provides the molecular basis for resource allocation among parents and their offspring, providing an important way to benefit the next generation.Abbreviations: ATG: autophagy-related; Becn1: beclin 1, autophagy related; CMA: chaperone-mediated autophagy; epg: ectopic PGL granules; ES: ectoplasmic specialization; EVTs: extravillous trophoblasts; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; PCD: programmed cell death; PTB: preterm birth; STB: syncytiotrophoblast.

3.
Adv Exp Med Biol ; 1206: 359-374, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31776994

RESUMO

Autophagy is a conserved catabolic process that delivers intracellular proteins and organelles to the lysosome for degradation and recycling. Evidences over the past decades have proved that autophagy participates in cell fate decision and also plays a key role in regulating cellular energy and nutrient stores. Lipid droplets (LDs) are the main lipid storage form in living organisms. The process of autophagic degradation of LDs is referred to lipophagy or macrolipophagy. Lipophagy is not only indispensable for the cellular lipid metabolism but also closely associated with several metabolic disorders such as obesity, hepatic steatosis, atherosclerosis, and so on. Here, we summarize recent progress in understanding the molecular mechanisms of lipophagy regulation and the emerging roles of lipophagy in various biological processes and metabolic disorders.


Assuntos
Autofagia , Metabolismo dos Lipídeos , Humanos , Gotículas Lipídicas , Lisossomos , Doenças Metabólicas/fisiopatologia , Pesquisa/tendências
4.
Adv Exp Med Biol ; 1206: 453-468, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31776998

RESUMO

Autophagy, a major degradation/recycling pathway, plays an essential role in cellular homeostasis maintenance, cell fate decision, and reproductive development. During reproduction, sperms and eggs, the specialized haploid gametes produced by the meiotic process of the germ cells in male and female respectively, are fused to form a new zygote that develops into fetus through embryogenesis and maternal-fetal crosstalk. Researches carried out in the past few years have proved that autophagy plays a key role in the regulation of reproduction process, and blockage of autophagy process likely contributes to reproductive abnormalities and even infertility. Here we summerize the recent progress in exploring the functional roles of autophagy in reproductive processes, such as spermatogenesis, folliculogenesis, fertilization, embryogenesis, and maternal-fetal crosstalk, in both animals and plants.


Assuntos
Autofagia , Reprodução , Animais , Feminino , Humanos , Infertilidade , Masculino , Reprodução/fisiologia , Espermatogênese/fisiologia , Espermatozoides
5.
Front Cell Dev Biol ; 7: 195, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31620437

RESUMO

During sexual reproduction, two haploid gametes fuse to form the zygote, and the acrosome is essential to this fusion process (fertilization) in animals. The acrosome is a special kind of organelle with a cap-like structure that covers the anterior portion of the head of the spermatozoon. The acrosome is derived from the Golgi apparatus and contains digestive enzymes. With the progress of our understanding of acrosome biogenesis, a number of models have been proposed to address the origin of the acrosome. The acrosome has been regarded as a lysosome-related organelle, and it has been proposed to have originated from the lysosome or the autolysosome. Our review will provide a brief historical overview and highlight recent findings on acrosome biogenesis in mammals.

6.
Oxid Med Cell Longev ; 2019: 9702562, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428232

RESUMO

Extracellular vesicles (EVs) are a heterogeneous group of membrane-bounded vesicles that are believed to be produced and secreted by presumably all cell types under physiological and pathological conditions, including tumors. EVs are very important vehicles in intercellular communications for both shorter and longer distances and are able to deliver a wide range of cargos including proteins, lipids, and various species of nucleic acids effectively. EVs have been emerging as a novel biotherapeutic platform to efficiently deliver therapeutic cargos to treat a broad range of diseases including cancer. This vast potential of drug delivery lies in their abilities to carry a variety of cargos and their ease in crossing the biological membranes. Similarly, their presence in a variety of body fluids makes them a potential biomarker for early diagnosis, prognostication, and surveillance of cancer. Here, we discuss the relatively least and understudied aspects of EV biology and tried to highlight the obstacles and limitations in their clinical applications and also described most of the new warfronts to beat cancer at multiple stages. However, much more challenges still remain to evaluate EV-based therapeutics, and we are very much hopeful that the current work prompts further discovery.


Assuntos
Vesículas Extracelulares/metabolismo , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Biomarcadores/metabolismo , Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Portadores de Fármacos/química , Vesículas Extracelulares/química , Vesículas Extracelulares/imunologia , Humanos , MicroRNAs/metabolismo , Neoplasias/diagnóstico , Neoplasias/imunologia
7.
Bosn J Basic Med Sci ; 19(1): 31-42, 2019 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-30599090

RESUMO

Spermatogenesis is a tightly controlled, multi-step process in which mature spermatozoa are produced. Disruption of regulatory mechanisms in spermatogenesis can lead to male infertility, various diseases of male reproductive system, or even cancer. The spermatogenic impairment in infertile men can be associated with different etiologies, and the exact molecular mechanisms are yet to be determined. MicroRNAs (miRNAs) are a type of non-protein coding RNAs, about 22 nucleotides long, with an essential role in post-transcriptional regulation. miRNAs have been recognized as important regulators of various biological processes, including spermatogenesis. The aim of this review is to summarize the recent literature on the role of miRNAs in spermatogenesis, male infertility and reproductive cancers, and to evaluate their potential in diagnosis, prognosis and therapy of disease. Experimental evidence shows that aberrant expression of miRNAs affects spermatogenesis at multiple stages and in different cell types, most often resulting in infertility. In more severe cases, dysregulation of miRNAs leads to cancer. miRNAs have enormous potential to be used as diagnostic and prognostic markers as well as therapeutic targets in male infertility and reproductive system diseases. However, to exploit this potential fully, we need a better understanding of miRNA-mediated regulation of spermatogenesis, including the characterization of yet unidentified miRNAs and related regulatory mechanisms.


Assuntos
Neoplasias dos Genitais Masculinos/genética , Infertilidade Masculina/genética , MicroRNAs/genética , Animais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Regulação da Expressão Gênica no Desenvolvimento , Neoplasias dos Genitais Masculinos/diagnóstico , Humanos , Infertilidade Masculina/diagnóstico , Masculino , Espermatogênese/genética
8.
Can J Gastroenterol Hepatol ; 2018: 4739637, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29850455

RESUMO

This study was aimed to find histological changes in the extrahepatic organs, hepatic iron deposition, and gene expression of some iron regulatory proteins in rats after sterile muscle abscess during the acute intoxication of Nerium oleander leaves decoction. 10 ml/kg of the leaves extract was injected intramuscularly in Wistar rats (200-225 g, n = 4). Control animals received saline injection of matched volume. Animals were anesthetized and sacrificed after 3, 6, 12, and 24 h after administration of decoction. Lungs, kidney, spleen, and liver were extracted and processed for histopathological examination while portion of liver tissue was proceeded for iron regulatory gene expression quantification. Sections of all studied organs were found with signs of cellular dysfunction with infiltration of variety of leucocytes. In the lungs section at 3 h time point mononuclear cell infiltrates were observed while in alveolar tissue at 24 h time point dilation and even collapse in some of the alveoli were evident. In kidney sections distortion of renal tubules and epithelial cells with shrinkage of glomeruli was noted at all studied time points. In the splenic section of 12 h time point, degeneration, depopulation, and shrinkage of white pulp have been noted. Distension of the red pulp along with activation of splenic follicles was evident after 24 h onset of APR. Significant changes in the expression of acute phase cytokine and iron regulatory genes were noted. IL-6 and Hepc gene expression were strongly upregulated up to 12 h whereby Tf gene expression showed an early upregulation at 3 h time point followed by downregulation on later points while Hjv gene expression showed an overall downregulation at all study time points compared to control. It is concluded that inherent toxins present in the N. oleander can induce acute phase response and cause severe histological changes in the organs and marked changes in the regulation of iron regulatory proteins thus cannot be practiced routinely.


Assuntos
Insuficiência de Múltiplos Órgãos/induzido quimicamente , Insuficiência de Múltiplos Órgãos/patologia , Nerium/toxicidade , Folhas de Planta , Animais , Biópsia por Agulha , Modelos Animais de Doenças , Imuno-Histoquímica , Rim/efeitos dos fármacos , Rim/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Paquistão , RNA/análise , Distribuição Aleatória , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real/métodos , Valores de Referência , Baço/efeitos dos fármacos , Baço/patologia
9.
Front Biosci (Schol Ed) ; 10: 119-126, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28930521

RESUMO

Human genome project unveiled that only 1.5.-2.0.% of the genome is protein coding. ENCODE and related studies showed that most part of the genome transcribed into RNAs, and most of them do not code for a functional proteins, hence the name non-coding RNAs (ncRNAs). ncRNAs are small ncRNAs (less than 200 nucleotides) and long ncRNAs (longer than 200 nucleotides up to 10 kb). They act as a direct link between highly ordered chromosome structures, gene expression and serve as a bridge between genome and chromatin modification complexes as guides, scaffolds, and decoys. Highly regulated hematopoietic differentiation is required for formation of all types of blood cells. Among a variety of lncRNAs only few hematopoitic lncRNAs have been studied extensivelyand most of them are not functionally characterized. The role of these lncRNAs remains partially undetermined but their involvement in the regulation of various genes and protein synthesis has been proved even in hematopoiesis. So, the present review is a mere effort to highlight the role of lncRNAs involved in the development and regulation of hematopoiesis.


Assuntos
Hematopoese/genética , RNA Longo não Codificante/genética , Animais , Diferenciação Celular/genética , Humanos
10.
Am J Transl Res ; 9(11): 4726-4737, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29218075

RESUMO

Interleukin-32 theta (IL-32θ) is newly identified isoform of IL-32 which plays a vital role in inflammatory responses. Like IL-32α and IL-32ß, IL-32θ isoform acts as an intracellular inflammatory modulator. It results in reduction of IL-1ß production by attenuating the expression of PU.1 and inhibition of monocytes differentiation into macrophages. IL-32θ hinders TNF-α expression by inhibiting p38 MAPK and inhibitor of κB (IκB) as well. It also reserved STAT3-ZEB1 pathway leading to the inhibition of epithelial-mesenchymal transition (EMT) and stemness. Hence, it can be concluded that IL-32θ is an anti-inflammatory cytokine that can act as a tumor suppressor and can play vital role in colon cancer therapies. IL-32θ also plays a crucial role in immune system responses and cellular differentiation during disease pathogenesis. To our best knowledge this is the first ever review to condense the importance, precise mode of action in disease progression and latent remedial implications of IL-32θ in several inflammatory disorders.

11.
Reproduction ; 154(3): R65-R79, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28696245

RESUMO

Meiosis is a specialized process that produces haploid gametes from diploid cells by a single round of DNA replication followed by two successive cell divisions. It contains many special events, such as programmed DNA double-strand break (DSB) formation, homologous recombination, crossover formation and resolution. These events are associated with dynamically regulated chromosomal structures, the dynamic transcriptional regulation and chromatin remodeling are mainly modulated by histone modifications, termed 'histone codes'. The purpose of this review is to summarize the histone codes that are required for meiosis during spermatogenesis and oogenesis, involving meiosis resumption, meiotic asymmetric division and other cellular processes. We not only systematically review the functional roles of histone codes in meiosis but also discuss future trends and perspectives in this field.


Assuntos
Código das Histonas , Meiose/fisiologia , Oogênese/fisiologia , Espermatogênese/fisiologia , Animais , Montagem e Desmontagem da Cromatina , Humanos
12.
Mediators Inflamm ; 2016: 8413768, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27143819

RESUMO

A vast variety of nonstructural proteins have been studied for their key roles and involvement in a number of biological phenomenona. Interleukin-32 is a novel cytokine whose presence has been confirmed in most of the mammals except rodents. The IL-32 gene was identified on human chromosome 16 p13.3. The gene has eight exons and nine splice variants, namely, IL-32α, IL-32ß, IL-32γ, IL-32δ, IL-32ε, IL-32ζ, IL-32η, IL-32θ, and IL-32s. It was found to induce the expression of various inflammatory cytokines including TNF-α, IL-6, and IL-1ß as well as macrophage inflammatory protein-2 (MIP-2) and has been reported previously to be involved in the pathogenesis and progression of a number of inflammatory disorders, namely, inflammatory bowel disease (IBD), gastric inflammation and cancer, rheumatoid arthritis, and chronic obstructive pulmonary disease (COPD). In the current review, we have highlighted the involvement of IL-32 in gastric cancer, gastric inflammation, and chronic rhinosinusitis. We have also tried to explore various mechanisms suspected to induce the expression of this extraordinary cytokine as well as various mechanisms of action employed by IL-32 during the mediation and progression of the above said problems.


Assuntos
Gastrite/imunologia , Gastrite/metabolismo , Interleucinas/metabolismo , Sinusite/imunologia , Sinusite/metabolismo , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/metabolismo , Animais , Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Doença Crônica , Humanos , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/metabolismo , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/metabolismo
13.
J Immunol Res ; 2016: 2148129, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28050571

RESUMO

Interleukin-22 (IL-22) is a pluripotent T cell-derived cytokine which is a member of IL-10 cytokine family. It is the only interleukin produced by immune cells but does not target immune system components. IL-22 is mainly produced by dendritic cells (DCs) and TH17, TH22, NK, and NKT cells and targets a number of body tissues including liver, pancreas, and other epithelial tissues. It provokes a series of downstream signaling pathways upon binding with IL-22R complex which protects liver damage through STAT3 activation. IL-22BP is an inhibitor of IL-22 which has 20-1000x more affinity to bind with IL-22 compared to IL-22R1 that inhibits IL-22 activity. Its level was found to be positively correlated with the severity of liver damage and fibrosis. So, the present review is an effort to reveal the exact mechanism lying in the hepatoprotective activity of IL-22 and some of its future therapeutic implications.


Assuntos
Interleucinas/metabolismo , Cirrose Hepática/prevenção & controle , Regeneração Hepática/imunologia , Receptores de Interleucina/metabolismo , Fator de Transcrição STAT3/metabolismo , Células Dendríticas/imunologia , Humanos , Interleucinas/imunologia , Células Matadoras Naturais/imunologia , Cirrose Hepática/imunologia , Células T Matadoras Naturais/imunologia , Receptores de Interleucina/imunologia , Transdução de Sinais/imunologia , Células Th17/imunologia
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