RESUMEN

Celiac disease, characterized as an autoimmune disorder, possesses the capacity to affect multiple organs and systems. Earlier research has indicated an increased risk of kidney diseases associated with celiac disease. However, the potential causal relationship between genetic susceptibility to celiac disease and the risk of kidney diseases remains uncertain. We conducted Mendelian randomization analysis using nonoverlapping European population data, examining the link between celiac disease and 10 kidney traits in whole-genome association studies. We employed the inverse variance-weighted method to enhance statistical robustness, and results' reliability was reinforced through rigorous sensitivity analysis. Mendelian randomization analysis revealed a genetic susceptibility of celiac disease to an increased risk of immunoglobulin A nephropathy (OR = 1.44; 95% confidence interval [CI] = 1.17-1.78; P = 5.7 × 10-4), chronic glomerulonephritis (OR = 1.15; 95% CI = 1.08-1.22; P = 2.58 × 10-5), and a decline in estimated glomerular filtration rate (beta = -0.001; P = 2.99 × 10-4). Additionally, a potential positive trend in the causal relationship between celiac disease and membranous nephropathy (OR = 1.37; 95% CI = 1.08-1.74; P = 0.01) was observed. Sensitivity analysis indicated the absence of pleiotropy. This study contributes novel evidence establishing a causal link between celiac disease and kidney traits, indicating a potential association between celiac disease and an elevated risk of kidney diseases. The findings provide fresh perspectives for advancing mechanistic and clinical research into kidney diseases associated with celiac disease.

Asunto(s)

Enfermedad Celíaca , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Enfermedad Celíaca/genética , Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/epidemiología , Humanos , Enfermedades Renales/genética , Enfermedades Renales/epidemiología , Enfermedades Renales/etiología , Tasa de Filtración Glomerular , Glomerulonefritis por IGA/genética , Glomerulonefritis por IGA/epidemiología , Causalidad , Glomerulonefritis Membranosa/genética , Glomerulonefritis Membranosa/epidemiología

RESUMEN

Enterovirus C116 (EV-C116) is a new member of the enterovirus C group which is closely associated with several infectious diseases. Although sporadic studies have detected EV-C116 in clinical samples worldwide, there is currently limited information available. In this study, two EV-C-positive fecal specimens were detected in apparently healthy children, which harbored low abundance, through meta-transcriptome sequencing. Based on the prototypes of several EV-Cs, two lineages were observed. Lineage 1 included many types that could not cause EV-like cytopathic effect in cell culture. Three genogroups of EV-C116 were divided in the maximum likelihood tree, and the two strains in this study (XZ2 and XZ113) formed two different lineages, suggesting that EV-C116 still diffuses worldwide. Obvious inter-type recombination events were observed in the XZ2 strain, with CVA22 identified as a minor donor. However, another strain (XZ113) underwent different recombination situations, highlighting the importance of recombination in the formation of EV-Cs biodiversity. The EV-C116 strains could propagate in rhabdomyosarcoma cell cultures at low titer; however, EV-like cytopathic effects were not observed. HEp-2, L20B, VERO, and 293T cell lines did not provide an appropriate environment for EV-C116 growth. These results challenge the traditional recognition of the uncultured nature of EV-C116 strains and explain the difficulty of clinical detection.

Asunto(s)

Infecciones por Enterovirus , Enterovirus , Niño , Humanos , Enterovirus/genética , Infecciones por Enterovirus/epidemiología , China/epidemiología , Antígenos Virales , Células HEK293

RESUMEN

BACKGROUND: The pain caused by recurrent aphthous stomatitis (RAS) and the recurrent nature of RAS lead to diminished quality of life for RAS patients. An alternative treatment for RAS is the oral administration of the Chinese herbal medicine Zhibai Dihuang pill (ZBDHP). Our study aims to investigate the clinical efficacy of ZBDHP when used in combination with Western medicine (WM) for the treatment of RAS and its effectiveness in preventing the recurrence of RAS. METHODS: Following the PRISMA 2020 guidelines, we conducted a literature search on 7 electronic databases according to predefined criteria. The methodological quality of randomized controlled trials (RCTs) was evaluated based on the Cochrane Handbook, and data analysis was performed using RevMan 5.3 software. RESULTS: A meta-analysis which included 7 studies and 669 participants in total was carried out in this study. The quantitative analysis revealed that the combined treatment of ZBDHP and WM has witnessed significantly improved overall clinical efficacy (RR = 1.20, 95% CI [1.12, 1.28], P < .05), reduced recurrence rate (RR = 0.24, 95% CI [0.13, 0.45], P < .05), decreased ulcer area (MD = -0.75, 95% CI [-0.91, -0.59], P < .05), and reduced pain visual simulation score (MD = -0.42, 95% CI [-0.52, -0.33], P < .05). No significant heterogeneity was observed among the studies. Qualitative analysis showed that the combination therapy significantly reduced serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 and interleukin-10, shortened ulcer healing time and pain disappearance time, with no adverse effects observed. CONCLUSION: It was found that the combination of ZBDHP and WM is more effective in treating RAS than the use of WM alone, which thus provides clinicians with a more optimal treatment option. However, due to limitations in the methodological quality of the included original studies and the small sample size, we hold the opinion that more rigorous and scientific clinical trials are needed to further evaluate the efficacy of ZBDHP in treating RAS.

Asunto(s)

Medicamentos Herbarios Chinos , Estomatitis Aftosa , Humanos , Medicamentos Herbarios Chinos/uso terapéutico , Estomatitis Aftosa/tratamiento farmacológico , Úlcera/tratamiento farmacológico , Dolor/tratamiento farmacológico

RESUMEN

Nutrient resorption is a fundamental physiological process in plants, with important ecological controls over numerous ecosystem functions. However, the role of community assembly in driving responses of nutrient resorption to perturbation remains largely unknown. Following the Price equation framework and the Community Assembly and Ecosystem Function framework, we quantified the contribution of species loss, species gain, and shared species to the reduction of community-level nutrient resorption efficiency in response to multi-level nitrogen (N) addition in a temperate steppe, after continuous N addition for seven years. Reductions of both N and phosphorus (P) resorption efficiency (NRE and PRE, respectively) were positively correlated with N addition levels. The dissimilarities in species composition between N-enriched and control communities increased with N addition levels, and N-enriched plots showed substantial species losses and gains. Interestingly, the reduction of community-scale NRE and PRE mostly resulted from N-induced decreases in resorption efficiency for the shared species in the control and N-enriched communities. There were negative correlations between the contributions of species richness effect and species identity effect and between the number and identity of species gained for the changes in both NRE and PRE following N enrichment. By simultaneously considering N-induced changes in species composition and in species-level resorption, our work presents a more complete picture of how different community assembly processes contribute to N-induced changes in community-level resorption.

Asunto(s)

Ecosistema , Nitrógeno , Nitrógeno/análisis , Plantas , Fósforo , Nutrientes , Suelo , Hojas de la Planta/química

RESUMEN

Recent findings found that TiO2 nanoparticles (TiO2-NPs) have male reproductive toxicity. However, few reports have studied the toxicity of TiO2-NPs in crustaceans. In this study, we first chose the freshwater crustacean Eriocheir sinensis (E. sinensis) to explore the male toxicity of TiO2-NP exposure and the underlying mechanisms. Three nm and 25 nm TiO2-NPs at a dose of 30 mg/kg bw induced apoptosis and damaged the integrity of the haemolymph-testis-barrier (HTB, a structure similar to the blood-testis-barrier) and the structure of the seminiferous tubule. The 3-nm TiO2-NPs caused more severe spermatogenesis dysfunction than the 25-nm TiO2-NPs. We initially confirmed that TiO2-NP exposure affected the expression patterns of adherens junctions (α-catenin and ß-catenin) and induced tubulin disorganization in the testis of E. sinensis. TiO2-NP exposure caused reactive oxygen species (ROS) generation and an imbalance of mTORC1-mTORC2 (mTORC1/rps6/Akt levels were increased, while mTORC2 activity was not changed). After using the ROS scavenger NAC to inhibit ROS generation, both the mTORC1-mTORC2 imbalance and alterations in AJs were rescued. More importantly, the mTORC1 inhibitor rapamycin abolished mTORC1/rps6/Akt hyperactivation and partially restored the alterations in AJs and tubulin. Collectively, the mTORC1-mTORC2 imbalance induced by TiO2-NPs was involved in the mechanism of AJ and HTB disruption, resulting in spermatogenesis in E. sinensis.

Asunto(s)

Nanopartículas , Testículo , Masculino , Humanos , Testículo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Tubulina (Proteína)/metabolismo , Uniones Adherentes/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Espermatogénesis/fisiología , Titanio/toxicidad , Titanio/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Nanopartículas/toxicidad , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Diana Mecanicista del Complejo 2 de la Rapamicina/metabolismo

RESUMEN

OBJECTIVE: This study investigated the relationship between the glucocorticoid-induced transcript 1 (GLCCI1) gene variant and the degree of improvement in lung function with inhaled corticosteroids (ICS). METHODS: We searched the PubMed, Embase, Cochrane Library, CBM, CNKI and Wanfang databases to obtain studies on the GLCCI1 rs37973 variant and the efficacy of ICS in asthma. RESULTS: The overall meta-analysis showed that patients with the GG phenotype (mutant homozygotes) exhibited significantly smaller forced expiratory volume in 1 sec (FEV1) change than patients with the AG phenotype (mutant heterozygous) (MD = -0.08, 95% CI [-0.12, -0.03], P = 0.001). Compared with the AA phenotype (wild homozygotes), the GG phenotype (MD = -4.23, 95% CI [-6.09, -2.38], P < 0.00001) and AG phenotype (MD = -1.92, 95% CI [-2.35, -1.49], P < 0.00001) had significantly smaller FEV1%pred changes. The FEV1 change subgroup analysis showed that the GG phenotype group was smaller than the AA phenotype group at 8 (MD = -0.53, 95% CI [-0.91, -0.14], P = 0.007), 12 (MD = -0.16, 95% CI [-0.30, -0.02], P = 0.02) and 24 (MD = -0.09, 95% CI [-0.17, -0.01], P = 0.02) weeks of treatment; the GG phenotype group was smaller than the AG phenotype group at 12 weeks (MD = -0.08, 95% CI [-0.15, -0.01], P = 0.02). CONCLUSION: This meta-analysis suggests that the GLCCI1 rs37973 variant affects the efficacy of ICS and that the presence of the G allele attenuates the improvement in lung function with ICS.

Asunto(s)

Antiasmáticos , Asma , Humanos , Receptores de Glucocorticoides/genética , Genotipo , Asma/tratamiento farmacológico , Asma/genética , Corticoesteroides/uso terapéutico , Glucocorticoides/uso terapéutico , Administración por Inhalación

RESUMEN

INTRODUCTION: The aim of this meta-analysis was to evaluate the effects of acellular nerve grafts (ANGs) with bone marrow mesenchymal stem cells (BMSCs) or Schwann cells (SCs) on the treatment of sciatic nerve defect in rats. EVIDENCE ACQUISITION: Electronic databases were accessed to identify eligible targets. ANGs data were extracted for meta-analysis using Review Manager 5.3. EVIDENCE SYNTHESIS: The rats subjected to ANGs+BMSCs or ANGs+SCs are characterized by different sciatic nerve function index, nerve conduction, latency, amplitude, myelin sheath thickness, myelinated nerve fibers and gastrocnemius wet weight. accompanied with evidently superior recovery of limb function. These differences are of statistical significance (P<0.05) when compared to that of control group with ANGs only. CONCLUSIONS: ANGs with BMSCs or SCs can promote nerve regeneration and functional recovery in peripheral nerve defects.

Asunto(s)

Células Madre Mesenquimatosas , Células de Schwann , Ratas , Animales , Ratas Sprague-Dawley , Células de Schwann/trasplante , Regeneración Nerviosa/fisiología , Nervio Ciático

RESUMEN

Cell adhesion and stable signaling regulation are fundamental ways of maintaining homeostasis. Among them, the Wnt/ß-CATENIN signaling plays a key role in embryonic development and maintenance of body dynamic homeostasis. At the same time, the key signaling molecule ß-CATENIN in the Wnt signaling can also function as a cytoskeletal linker protein to regulate tissue barriers, cell migration, and morphogenesis. Dysregulation of the balance between Wnt signaling and adherens junctions can lead to disease. How ß-CATENIN maintains the independence of these two functions, or mediates the interaction and balance of these two functions, has been explored and debated for a long time. In this study, we will focus on five aspects of ß-CATENIN chaperone molecules, phosphorylation of ß-CATENIN and related proteins, epithelial mesenchymal transition, ß-CATENIN homolog protein γ-CATENIN and disease, thus deepening the understanding of the Wnt/ß-CATENIN signaling and the homeostasis between cell adhesion and further addressing related disease problems.

Asunto(s)

Vía de Señalización Wnt , beta Catenina , beta Catenina/metabolismo , Adhesión Celular , Vía de Señalización Wnt/fisiología , Movimiento Celular , Fosforilación

RESUMEN

Objective: To investigate the clinical characteristics of patients with acute phosphine poisoning, and to follow up and evaluate the prognosis of patients. Methods: In May 2022, 12 patients with phosphine poisoning by respiratory inhalation in Beijing Chao-Yang Hospital of Capital Medical University were analyzed. The patients were treated with symptomatic support therapy. Three months later, patients were re-evaluated the symptoms of poisoning, pulmonary function and magnetic resonance imaging (MRI) of the brain to understand the prognosis of the phosphine poisoning. Results: The main symptoms of 12 patients were respiratory and central nervous system symptoms with hypoxia. The symptoms of poisoning improved after treatment. Follow-up found that the patients had different degrees of residual symptoms. Pulmonary function showed increased airway resistance. Airway challenge test was positive in some patients. MRI of the head of some patients showed small ischemic focus in bilateral frontal lobes. Conclusion: Acute phosphine poisoning may cause persistent damage to the respiratory system and central system, and residual symptoms after 3 months.

Asunto(s)

Humanos , Estudios de Seguimiento , Fosfinas , Pulmón , Enfermedades Pulmonares , Compuestos de Aluminio , Intoxicación/diagnóstico

RESUMEN

To evaluate the quality and quantify bioactive constituents in different parts of Angelicae Sinensis Radix, an efficient, high-speed, high-sensitivity high-performance liquid chromatography and triple quadrupole mass spectrometry method was used for simultaneous detection of 12 chemical compounds including L-tryptophan, chlorogenic acid, caffeic acid, ferulic acid, isoferulic acid, senkyunolide I, guanosine, proline, L-glutamine, γ-aminobutyric acid, glutamic acid, and arginine in 52 batches of Angelicae Sinensis Radix from Gansu, China. The established methods were validated by good linearity (R2≥0.9921), limits of detection (0.0001-0.0156 µg/mL), limits of quantitation (0.0006-0.0781 µg/mL), stability (RSD≤7.77%), repeatability (RSD≤6.79%), intra- and interday precisions (RSD≤6.00% and RSD≤6.39%, respectively) and recovery (90.90-107.16%). According to the quantitative results, the contents of the hydrophilic compounds were higher in the head, while the medium and weak polar components were mainly concentrated in the tail. Finally, principal component analysis results revealed that Angelicae Sinensis Radix could be divided into different medicinal sites based on polar components such as amino acids, nucleosides. The combination of liquid chromatography-tandem mass spectrometry and principal component analysis is a simple and reliable method for pattern recognition and quality evaluation of Angelicae Sinensis Radix.

Asunto(s)

Angelica sinensis , Medicamentos Herbarios Chinos , Espectrometría de Masas en Tándem/métodos , Quimiometría , Angelica sinensis/química , Cromatografía Liquida , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química

RESUMEN

There are two kinds of toxins in sea anemones: neurotoxins and pore forming toxins. As a representative of the sodium channel toxin, the neurotoxin ATX II in neurotoxin mainly affects the process of action potential and the release of transmitter to affect the inactivation of the sodium channel. As the representatives of potassium channel toxins, BgK and ShK mainly affect the potassium channel current. EqTx and Sticholysins are representative of pore forming toxins, which can form specific ion channels in cell membranes and change the concentration of internal and external ions, eventually causing hemolytic effects. Based on the above mechanism, toxins such as ATX II can also cause toxic effects in tissues and organs such as heart, lung and muscle. As an applied aspect it was shown that sea anemone toxins often have strong toxic effects on tumor cells, induce cancer cells to enter the pathway of apoptosis, and can also bind to monoclonal antibodies or directly inhibit relevant channels for the treatment of autoimmune diseases.

Asunto(s)

Neurotoxinas , Anémonas de Mar , Animales , Neurotoxinas/toxicidad , Neurotoxinas/metabolismo , Anémonas de Mar/metabolismo , Canales de Sodio/metabolismo , Canales de Sodio/farmacología , Canales de Potasio/metabolismo , Canales de Potasio/farmacología , Membrana Celular/metabolismo

RESUMEN

OBJECTIVE: The present study aims to explore the correlation of the transforming growth factor ß (TGF-ß), drosophila mothers against decapentaplegic protein gene (SMAD) 2/3/4, and leukemia inhibitory factors (LIF) with the cyst formation of hepatic Echinococcus granulosus in young children. METHODS: A total of 40 patients who met the diagnostic criteria for children's hydatid disease in people's Hospital of Xinjiang Uygur Autonomous Region between January 2020 and June 2021 were enrolled a s the study subjects. The cystic fluid of these children was collected as the case group and the corresponding infected viscera or pericystic tissue as the control group, with 40 cases in each group. In vitro cultured protoscolice of hydatid cyst, four groups including control group, LIF siRNA group, LIF factor group and SMAD4 siRNA group were divided by inhibiting TGF-ß/SMADs signal pathway. Each assay was performed in triplicate. The expression of TGF-ß, SMAD2/3/4 and LIF were detected. RESULTS: The results of the clinical trial showed that the contents of SMAD2 and SMAD3 were increased in the case group compared with the control group; the differences were statistically significant (P < 0.05). The expression levels of TGF-ß, Smad4, and LIF increased in the case group compared with the control group; however, the differences were not statistically significant. The results of further in vitro experiments, the expression levels of TGF-ß, SMAD 2/3/4, and LIF after adding siRNA to interfere with Smad4 decreased in the case group compared with the control group; the differences were statistically significant (P < 0.05). Compared with the control group, the expression levels of TGF-ß, SMAD2/3/4, and LIF increased after treatment with added LIF in the case group, and the expression levels of TGF-ß, SMAD2/3/4, and LIF decreased after adding siRNA to interfere with LIF in the case group; the differences were all statistically significant (P < 0.05). CONCLUSION: SMAD2 and SMAD3 have a certain clinical relevance with hydatidosis in young children. The LIF expression level may be related to the cystic transformation of protoscoleces. It has been suggested that the TGF-ß/Smads/LIF signaling pathway may be present in the process of protoscoleces cyst formation; this provides a research basis for the prevention and treatment of post-infection parasitism of E. multilocularis eggs in young children.

Asunto(s)

Quistes , Echinococcus , Animales , ARN Interferente Pequeño , Factor de Crecimiento Transformador beta

RESUMEN

Two polysaccharides from Carthamus tinctorius L. (CTLP-1 and CTLP-2) were purified, and their structures were analyzed by physical and chemical testing. CTLP-1 had a mass of 5900 Da that was composed of arabinose, glucose, and galactose with a mass molar ratio of 6.7:4.2:1. The backbone of CTLP-1 was →1)-α-GalAp-(1→4)-α-Arap-(1→2)-α-Glup-(4→. CTLP-2 had a mass of 8200 Da that was composed of arabinose, glucose, and galactose with a mass molar ratio of 16.76:4.28:1. The backbone of CTLP-2 was →1)-α-Galp-(2,6 →1)-α-Arap-(4,6 →1)-α-Glup-(3→. Both of them exhibited a high reducing power, hydroxyl radical scavenging activity, DPPH radical scavenging activity and ABTS radical scavenging activity, moderate Fe2+ chelating activity and superoxide anion scavenging activity, implying that they might be potential antioxidants.

RESUMEN

Objective: This study was to examine the anti-inflammatory effect of sappanone A on interleukin- (IL-) 1ß-stimulated osteoarthritis (OA) chondrocytes. Methods: Chondrocytes were pretreated with sappanone A for 2 h before subsequent IL-1ß stimulation. The mRNA expression levels of iNOs, COX-2, aggrecan, and collagen-II were measured with qRT-PCR. The levels of TNF-α, IL-6, IL-8, MMP-3, and MMP-13 were determined by ELISA. The protein levels of iNOs, COX-2, ADAMTS-4, ADAMTS-5, aggrecan, collagen-II, p-p65, p65, IκBα, Nrf2, and HO-1 were assessed by Western blot. Results: Sappanone A inhibited the IL-1ß-stimulated production of NO, PGE2, iNOS, COX-2, TNF-α, IL-6, and IL-8 in OA chondrocytes. In addition, sappanone A suppressed the expression of MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5 in IL-1ß-stimulated OA chondrocytes. The degradation of ECM components was reversed by sappanone A. Sappanone A prevented NF-κB activation while enhanced Nrf2/HO-1 activation in IL-1ß-treated chondrocytes. Conclusion: Sappanone A may be a potent therapeutic agent for OA.

Asunto(s)

Condrocitos , Osteoartritis , Agrecanos/metabolismo , Agrecanos/farmacología , Antiinflamatorios/uso terapéutico , Condrocitos/metabolismo , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 2/farmacología , Ciclooxigenasa 2/uso terapéutico , Dinoprostona/metabolismo , Dinoprostona/farmacología , Dinoprostona/uso terapéutico , Humanos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Isoflavonas , Metaloproteinasa 13 de la Matriz/genética , Metaloproteinasa 13 de la Matriz/metabolismo , Metaloproteinasa 13 de la Matriz/farmacología , Metaloproteinasa 3 de la Matriz/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Inhibidor NF-kappaB alfa/metabolismo , FN-kappa B/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismo , ARN Mensajero/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

Spermatogenesis is a finely regulated process of germ cell proliferation and differentiation that leads to the production of sperm in seminiferous tubules. Although the mammalian target of rapamycin (mTOR) signaling pathway is crucial for spermatogenesis in mammals, its functions and molecular mechanisms in spermatogenesis remain largely unknown in nonmammalian species, particularly in Crustacea. In this study, we first identified es-Raptor (the core component of mTOR complex 1) and es-Rictor (the core component of mTOR complex 2) from the testis of Eriocheir sinensis. Dynamic localization of es-Raptor and es-Rictor implied that these proteins were indispensable for the spermatogenesis of E. sinensis. Furthermore, es-Raptor and es-Rictor knockdown results showed that the mature sperm failed to be released, causing almost empty lumens in the testis. We investigated the reasons for these effects and found that the actin-based cytoskeleton was disrupted in the knockdown groups. In addition, the integrity of the testis barrier (similar to the blood-testis barrier in mammals) was impaired and affected the expression of cell junction proteins. Further study revealed that es-Raptor and es-Rictor may regulate spermatogenesis via both mTORC1- and mTORC2-dependent mechanisms that involve es-rpS6 and es-Akt/es-PKC, respectively. Moreover, to explore the testis barrier in E. sinensis, we established a cadmium chloride (CdCl2)-induced testis barrier damage model as a positive control. Morphological and immunofluorescence results were similar to those of the es-Raptor and es-Rictor knockdown groups. Altogether, es-Raptor and es-Rictor were important for spermatogenesis through maintenance of the actin filament network and cell junctions in E. sinensis.

Asunto(s)

Braquiuros , Semen , Animales , Masculino , Diana Mecanicista del Complejo 1 de la Rapamicina , Espermatogénesis/fisiología , Citoesqueleto de Actina , Uniones Intercelulares , Proteínas/farmacología , Mamíferos

RESUMEN

Male sterility is a worldwide health problem which has troubled many unfortunate families and attracted widespread attention in the field of reproduction. Retinoic acid (RA) is a metabolite of vitamin A. Previous studies have shown that insufficient intake of vitamin A can lead to male infertility. Similarly, RA-deficiency can lead to abnormal spermatogenesis in men. RA signaling is inseparable from hormone stimulation, such as FSH, testosterone and others. It can regulate spermatogenesis as well, including the proliferation and differentiation of spermatogonia, meiosis, spermiogenesis and spermiation. To promote or inhibit spermatogenesis, RA regulates Stra8, Kit, GDNF, BMP4 and other factors in various pathways. At the self-renewal stage, RA inhibits spermatogonia renewal by directly or indirectly inhibiting DMRT, GDNF and Cyclin. At the stage of differentiation and meiosis, RA controls SSC differentiation through Kit induction and Nanos2 inhibition, and controls spermatogonia meiotic entry through up- regulation of Stra8. At the stage of spermiogenesis, RARα945;, as a key regulator, regulates spermatogenesis by up regulating Stra8 while binding with RA. Although RA plays an important role in all stages of spermatogenesis, RA signaling is more important in the early stage of spermatogonia (spg) differentiation and spermatocyte(spc) meiosis. According to the principle of RA signaling that regulates spermatogenesis, we also speculate on the future clinical application of RA, such as potential induction of SSC in vitro, contraception and restoring spermatogenesis. This paper reviews the regulatory pathways of RA, and prospects the clinical applications of RA signaling in the future.

Asunto(s)

Tretinoina , Vitamina A , Masculino , Humanos , Transducción de Señal

RESUMEN

The generation of functional sperm relies on spermatogonial stem cells (SSCs) as they can maintain a stem cell pool for continuous generation of functional spermatozoa. The maintenance of SSCs is regulated by several factors. In this paper, we summarize the niche and intrinsic factors in regulating SSC self-renewal and proliferation. GDNF regulates SSC self-renewal through Ras-ERK1/2, SFC, PI3K/Akt and MEK/ERK-mTOR signaling pathways. FGF activates MAPK2K1, ERK and Akt pathways and EGF activates ERK and Akt pathways to induce SSC proliferation. Wnt ligands regulate SSC self-renewal and proliferation through both ß-catenin dependent and independent pathways. SCF1 and CXCL12 are also found to have roles in SSC maintenance. As for intrinsic factors in SSCs, ETV5, Bcl6b, Lhx1, ID4 and Nanos2 are regulated by niche factors. They act as the downstream factors of niche factors in regulating SSC self-renewal and proliferation. Transcriptional factors OCT4 and PLZF, as well as FOXO1 in SSCs can directly regulate SSC self-renewal and proliferation. Although we have identified the factors, the detailed mechanism of these factors in regulating SSC fate determination is largely unknown. Here, we summarize factors which have roles in SSC fate determination and hope it will be beneficial for further study and treatment of male infertility.

Asunto(s)

Autorrenovación de las Células , beta Catenina , Animales , Masculino , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Factor Neurotrófico Derivado de la Línea Celular Glial/farmacología , Proteínas Proto-Oncogénicas c-akt , Fosfatidilinositol 3-Quinasas , Ligandos , Factor de Crecimiento Epidérmico , Proliferación Celular , Semen/metabolismo , Mamíferos/metabolismo , Serina-Treonina Quinasas TOR , Quinasas de Proteína Quinasa Activadas por Mitógenos

RESUMEN

The PI3K/AKT signaling pathway is one of the most crucial regulatory mechanisms in animal cells, which can mainly regulate proliferation, survival and anti-apoptosis in cell lines. In the seminiferous epithelium, most studies were concentrated on the role of PI3K/AKT signaling in immature Sertoli cells (SCs) and spermatogonia stem cells (SSCs). PI3K/AKT signaling can facilitate the proliferation and anti-apoptosis of immature Sertoli cells and spermatogenic cells. Besides, in mature Sertoli cells, this pathway can disintegrate the structure of the blood-testis barrier (BTB) via regulatory protein synthesis and the cytoskeleton of Sertoli cells. All of these effects can directly and indirectly maintain and promote spermatogenesis in male testis.

Asunto(s)

Proteínas Proto-Oncogénicas c-akt , Células de Sertoli , Animales , Masculino , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Epitelio Seminífero/metabolismo , Células de Sertoli/metabolismo , Transducción de Señal , Espermatogénesis/fisiología , Testículo

RESUMEN

BACKGROUND: Pneumonia is a serious pediatric lung injury disease caused by Mycoplasma pneumoniae (M. pneumoniae) with increasing global prevalence every year. The WHO has reported that nearly 19% of children die due to pneumonia worldwide. OBJECTIVE: The present research was conducted to discover the ameliorative properties of geraniol against M. pneumoniae-provoked pneumonia in mice through the modulation of inflammatory responses. METHODOLOGY: The pneumonia was provoked in the male Swiss albino mice via infecting animals with 100 µl of M. pneumoniae for 2 days and supplemented concurrently with 20 mg/kg of geraniol for 3 days. 100 mg/kg of azithromycin was used as a standard drug. The nitric oxide (NO) level and MPO activity were measured using kits. The SOD activity, GSH, and MDA levels were studied using standard methods. The polymerase chain reaction (PCR) study was performed to examine the M. pneumoniae DNA load. The inflammatory cytokines status was assessed by assay kits. The ERK1/2, JNK1/2, and NF-κB expressions were studied by reverse-transcription (RT-PCR). The lung tissues were analyzed microscopically to investigate the histological alterations. RESULTS: Geraniol treatment effectively reduced lung weight, NO level, and MPO activity in the pneumonia mice. The total cells and M. pneumoniae DNA load were also decreased by the geraniol. The SOD activity and GSH level were improved and MDA was decreased by the geraniol treatment. The IL-1, IL-6, IL-8, TNF-α, and TGF status were appreciably depleted by the geraniol in the pneumonia mice. Geraniol also suppressed the ERK1/2 and NF-κB expressions in the lung tissues. Histological findings also suggest the therapeutic roles of geraniol against pneumonia in mice. CONCLUSION: In summary, our results proved the beneficial roles of geraniol against the M. pneumoniae-provoked pneumonia. Geraniol could be a hopeful therapeutic agent to treat pneumonia in the future.

Asunto(s)

Lesión Pulmonar , Neumonía por Mycoplasma , Monoterpenos Acíclicos , Animales , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Pulmón/metabolismo , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/etiología , Lesión Pulmonar/metabolismo , MAP Quinasa Quinasa 4/metabolismo , Masculino , Ratones , Mycoplasma pneumoniae/metabolismo , FN-kappa B/metabolismo , Neumonía por Mycoplasma/tratamiento farmacológico , Neumonía por Mycoplasma/metabolismo , Transducción de Señal , Superóxido Dismutasa/metabolismo

RESUMEN

Global climate change is a major threat to biodiversity, which may increase the extinction risk of rare species, particularly those like Ostrya rehderiana Chun (Betulaceae) with very few remaining extant wild individuals. We aimed to estimate the potential distribution of O. rehderiana under climate change and to analyze possible relevant climatic factors. Maximum entropy (Maxent) was employed to model the potential distribution of O. rehderiana under present and future climate scenarios. Suitable habitat areas in different periods and the main contributing climate factors were identified using species distribution models. The minimum temperature in winter and precipitation seasonality were the principal climatic factors influencing the establishment of O. rehderiana. The proportion of high potential distribution area in China was 3.91% and would further shrink significantly under changing climate, especially reduce by 97% under high radiative forcing. The extinction risk of O. rehderiana would still be extraordinarily high under future climate scenarios. The Tianmu and Luoxiao Mountains would be the only potential refugia for O. rehderiana in the future. Special conservation efforts are urgently required to rescue extremely endangered species as O. rehderiana. We propose priorities for the conservation region and suggestions for conservation management strategies.

Asunto(s)

Cambio Climático , Especies en Peligro de Extinción , Animales , Betulaceae , Biodiversidad , China , Ecosistema , Humanos