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1.
Biomolecules ; 13(1)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36671503

RESUMO

Strategies to promote dental pulp stem cells (DPSCs) functions including proliferation, migration, pro-angiogenic effects, and odontogenic/osteogenic differentiation are in urgent need to restore pulpitis-damaged dentin/pulp regeneration and DPSCs-based bone tissue engineering applications. Cannabidiol (CBD), an active component of Cannabis sativa has shown anti-inflammation, chemotactic, anti-microbial, and tissue regenerative potentials. Based on these facts, this study aimed to analyze the effect of CBD on DPSCs proliferation, migration, and osteogenic/odontogenic differentiation in basal and inflammatory conditions. Highly pure DPSCs with characteristics of mesenchymal stem cells (MSCs) were successfully isolated, as indicated by the results of flowcytometry and multi-lineage (osteogenic, adipogenic, and chondrogenic) differentiation potentials. Among the concentration tested (0.1-12.5 µM), CBD (2.5 µM) showed the highest anabolic effect on the proliferation and osteogenic/odontogenic differentiation of DPSCs. Pro-angiogenic growth factor VEGF mRNA expression was robustly higher in CBD-treated DPSCs. CBD also prompted the migration of DPSCs and CBD receptor CB1 and CB2 expression in DPSCs. TNF-α inhibited the viability, migration, and osteogenic/odontogenic differentiation of DPSCs and CBD reversed these effects. CBD alleviated the TNF-α-upregulated expression of pro-inflammatory cytokines TNF-α, interleukin (IL)-1ß, and IL-6 in DPSCs. In conclusion, our results indicate the possible application of CBD on DPSCs-based dentin/pulp and bone regeneration.


Assuntos
Canabidiol , Osteogênese , Osteogênese/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Canabidiol/farmacologia , Canabidiol/metabolismo , Polpa Dentária , Células-Tronco , Células Cultivadas , Regeneração , Diferenciação Celular , Proliferação de Células
2.
EBioMedicine ; 88: 104433, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36623453

RESUMO

BACKGROUND: Successful embryo implantation requires the attachment of a blastocyst to the receptive endometrial epithelium, which was disturbed in the women with recurrent implantation failure (RIF). Endometrial ß3-integrin was the most important adhesion molecule contributing to endometrial receptivity in both humans and mice. Nur77 has been proven indispensable for fertility in mice, here we explore the role of Nur77 on embryo-epithelial adhesion and potential treatment to embryo implantation failure. METHODS: The expression and location of Mst1 and Nur77 in endometrium from fertile women and RIF patients were examined by IHC, qRT-PCR and Western blotting. In vitro kinase assay following with LC-MS/MS were used to identify the phosphorylation site of Nur77 activated by Mst1. The phosphorylated Nur77 was detected by phos-tag SDS-PAGE assay and specific antibody against phospho-Nur77-Thr366. The effect of embryo-epithelium interaction was determined in the BeWo spheroid or mouse embryo adhesion assay, and delayed implantation mouse model. RNA-seq was used to explore the mechanism by which Nur77 derived peptide promotes endometrial receptivity. FINDINGS: Endometrial Mammalian sterile 20 (STE20)-like kinase 1 (Mst1) expression level was decreased in the women with RIF than that in the fertile control group, while Mst1 activation in the epithelial cells promoted trophoblast-uterine epithelium adhesion. The effect of Nur77 mediated trophoblast-uterine epithelium adhesion was facilitated by active Mst1. Mechanistically, mst1 promotes the transcription activity of Nur77 by phosphorylating Nur77 at threonine 366 (T366), and consequently increased downstream target ß3-integrin expression. Furthermore, a Nur77-derived peptide containing phosphorylated T366 markedly promoted mouse embryo attachment to Ishikawa cells ([4 (2-4)] vs [3 (2-4)]) and increased the embryo implantation rate (4 vs 1.4) in a delayed implantation mouse model by regulating integrin signalling. Finally, it is observed that the endometrial phospho-Nur77 (T366) level is decreased by 80% in the women with RIF. INTERPRETATION: In addition to uncovering a potential regulatory mechanism of Mst1/Nur77/ß3-integrin signal axis involved in the regulation of embryo-epithelium interaction, our finding provides a novel marker of endometrial receptivity and a potential therapeutic agent for embryo implantation failure. FUNDING: National Key Research and Development Program of China (2018YFC1004400), the National Natural Science Foundation of China (82171653, 82271698, 82030040, 81971387 and 30900727), and National Institutes of Health grants (R01HL103869).

3.
Rev. bras. med. esporte ; 29: e2021_0333, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1387954

RESUMO

ABSTRACT Periodontal disease (PD) is an inflammatory oral disease and alveolar bone loss is the most important sign of PD. However, the effects of exercise on inflammatory factors and alveolar bone loss in individuals with PD have been little studied. This meta-analysis assesses the effect of physical exercise on alveolar bone loss (ABL) and the inflammatory profile of PD in animal models. Relevant studies published through July 2020 in PubMed, Medline, Embase and Web of Science were searched after developing a PICOS statement. Quality assessment and risk of bias were analyzed according to the SYRCLE protocol. A total of 52 references were retrieved, 4 of which were considered eligible for inclusion. A total of thirty-four male Wistar rats from the included studies were evaluated for alveolar bone loss and assessed for inflammatory profile. The results indicated that physical exercise could reduce alveolar bone loss (95% CI -2.85 to -0.82, p = 0.002) and the pro-inflammatory tumor necrosis factor-α (TNF-α) in serum or gingival tissue (95% CI -0.45 to -0.24, p < 0.00001). Inversely, exercise increased anti-inflammatory interleukin-10 (IL-10) in serum or gingival tissue (95% CI 0.28 to 0.69, p < 0.00001). However, one study reported a negative result in the expression of TNF-α and IL-10. Current evidence indicates that physical exercise contributes to ameliorate PD by reducing alveolar bone loss and inflammation in animal PD models, which suggests that moderate exercise can be implemented in clinical practice to maintain periodontal health. Level of Evidence I; Systematic Review and Meta-analysis


RESUMEN La enfermedad periodontal (EP) es una enfermedad inflamatoria oral y la pérdida de hueso alveolar es su signo más importante. Sin embargo, los efectos del ejercicio sobre los factores inflamatorios y la pérdida ósea alveolar en individuos con EP han sido poco estudiados. Este meta-análisis evalúa el efecto del ejercicio sobre la pérdida ósea alveolar (POA) y el perfil inflamatorio de la EP en modelos animales. Se llevaron a cabo estudios relevantes publicados hasta julio de 2020 en PubMed, Medline, Embase y Web of Science tras desarrollar la investigación con el método PICO. La evaluación de la calidad y el riesgo de sesgo se analizaron según el protocolo SYRCLE. Se recuperó un total de 52 referencias, cuatro de las cuales se consideraron elegibles para su inclusión. En un total de 34 ratas Wistar macho de los estudios incluidos se evaluó la pérdida de hueso alveolar y el perfil inflamatorio. Los resultados indicaron que el ejercicio puede reducir la pérdida de hueso alveolar (IC del 95%: -2,85 a -0,82; p = 0,002) y el factor de necrosis tumoral proinflamatorio-α (TNFα) en suero o tejido gingival (IC del 95%: -0,45 a -0,24; p < 0,00001). Por el contrario, el ejercicio aumentó la interleucina-10 (IL-10) antiinflamatoria en el suero o en el tejido gingival (IC del 95%: 0,28 a 0,69; p < 0,00001). Sin embargo, un estudio informó de un resultado negativo en la expresión de TNFα e IL-10. Las pruebas actuales indican que el ejercicio contribuye a mejorar la EP al reducir la pérdida de hueso alveolar y la inflamación en modelos animales de EP, lo que sugiere que se puede implementar el ejercicio moderado en la práctica clínica para mantener la salud periodontal. Nivel de Evidencia I; Revisión Sistemática y Meta-análisis.


RESUMO A doença periodontal (DP) é uma doença inflamatória oral e a perda óssea alveolar é seu sinal mais importante. No entanto, os efeitos do exercício sobre os fatores inflamatórios e a perda óssea alveolar em indivíduos com DP têm sido pouco estudados. Esta metanálise avalia o efeito do exercício físico sobre a perda óssea alveolar (POA) e o perfil inflamatório da DP em modelos animais. Estudos relevantes publicados até julho de 2020 em PubMed, Medline, Embase e Web of Science foram pesquisados depois de desenvolver a pesquisa com o método PICO. A avaliação da qualidade e o risco de viés foram analisados de acordo com o protocolo SYRCLE. Um total de 52 referências foram recuperadas, quatro das quais foram consideradas elegíveis para inclusão. Um total de 34 ratos Wistar machos dos estudos incluídos foram avaliados quanto à perda de osso alveolar e avaliados quanto ao perfil inflamatório. Os resultados indicaram que o exercício físico pode reduzir a perda de osso alveolar (IC 95% -2,85 a -0,82, p = 0,002) e o fator de necrose tumoral pró-inflamatório-α (TNFα) no soro ou tecido gengival (IC 95% -0,45 a -0,24, p < 0,00001). Inversamente, o exercício aumentou a interleucina-10 anti-inflamatória (IL-10) no soro ou no tecido gengival (IC 95% 0,28 a 0,69, p < 0,00001). Contudo, um estudo relatou resultado negativo na expressão de TNFα e IL-10. As evidências atuais indicam que o exercício físico contribui para melhorar a DP, reduzindo a perda de osso alveolar e a inflamação em modelos animais de DP, o que sugere que o exercício moderado pode ser implementado na prática clínica para manter a saúde periodontal. Nível de Evidência I; Revisão Sistemática e Metanálise.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36535840

RESUMO

OBJECTIVES: This study aimed to use machine learning algorithms to build an efficient forecasting model of atrial fibrillation after cardiac surgery, and to compare the predictive performance of machine learning to traditional logistic regression. DESIGN: A retrospective study. SETTING: Second Affiliated Hospital of Zhejiang University School of Medicine. PARTICIPANTS: The study comprised 1,400 patients who underwent valve and/or coronary artery bypass grafting surgery with cardiopulmonary bypass from September 1, 2013 to December 31, 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two machine learning approaches (gradient-boosting decision tree and support-vector machine) and logistic regression were used to build predictive models. The performance was compared by the area under the curve (AUC). The clinical practicability was assessed using decision curve analysis. Postoperative atrial fibrillation occurred in 519 patients (37.1%). The AUCs of the support-vector machine, logistic regression, and gradient boosting decision tree were 0.777 (95% CI: 0.772-0.781), 0.767 (95% CI: 0.762-0.772), and 0.765 (95% CI: 0.761-0.770), respectively. As decision curve analysis manifested, these models had achieved appropriate net benefit. CONCLUSION: In the authors' study, the support-vector machine model was the best predictor; it may be an effective tool for predicting atrial fibrillation after cardiac surgery.

5.
Int J Mol Sci ; 23(22)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36430316

RESUMO

Severe environmental pollution problems arising from toxic dyestuffs (e.g., methyl orange) are receiving increasing attention. Therefore, dyes' safe removal has become a research hotspot. Among the many physical-chemical removal techniques, adsorption using renewable biological resources has proved to be more advantageous over others due to its effectiveness and economy. Chitosan is a natural, renewable biopolymer obtained by deactivated chitin. Thus, the magnetic resin of chitosan microspheres (MRCM), prepared by reversed-phase suspension cross-linking polymerization, was used to remove methyl orange from a solution in a batch adsorption system. The main results are as follows: (1) The results of physical and swelling properties of MRCM indicated that MRCM was a type of black spherical, porous, water-absorbing, and weak alkali exchange resin, and it had the ability to adsorb methyl orange when it was applied in solutions above pH 2.0. (2) In batch adsorption studies, the maximum adsorption capacity was obtained at pH 5; the adsorption equilibrium time was 140 min; and the maximum adsorption was reached at 450 mg/L initial concentration. (3) Among the three isotherm adsorption models, Langmuir achieved the best fit for the adsorption of methyl orange onto MRCM. (4) The adsorption thermodynamics indicated that the adsorption was spontaneous, with increasing enthalpy, and was driven by the entropy. (5) The pseudo-second-order kinetics equation was most suitable to describe the adsorption kinetics, and the adsorption kinetics was also controlled by the liquid-film diffusion dynamics. Consequently, MRCM with relatively higher methyl orange adsorption exhibited the great efficiency for methyl orange removal as an environment-friendly sorbent. Thus, the findings are useful for methyl orange pollution control in real-life wastewater treatment applications.


Assuntos
Quitosana , Adsorção , Quitosana/química , Cinética , Microesferas , Concentração de Íons de Hidrogênio , Termodinâmica , Fenômenos Magnéticos
6.
World J Clin Cases ; 10(29): 10638-10646, 2022 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-36312503

RESUMO

BACKGROUND: Preoperative conditions in pediatric liver transplant recipients are understandably complex. Compared with adults, children have lesser compensatory abilities and demand greater precision during procedural executions. In the setting of end-stage liver disease, the heightened perioperative risk of coexistent cardiovascular pathology may impact graft survival as well. Requirements for anesthesia and perioperative management are thus more rigorous, calling for individualized treatments that reflect specific cardiovascular constraints and proposed surgical plans. CASE SUMMARY: Reports of perioperative anesthesia management and liver transplant prognostication in pediatric patients with concurrent atrial septal defects are scarce. Herein, we detail the course of liver transplantation in a child with dual afflictions, focusing on perioperative anesthesia management and the important contributions of the anesthesiologist (pre- and perioperatively) to a positive therapeutic outcome, despite the clinical hurdles imposed. CONCLUSION: Children with atrial septal defects bear substantially more than customary perioperative risk during orthotopic liver transplants, given their compromised cardiopulmonary reserves and functional states. Comprehensive preoperative cardiovascular assessments, including use of agitated-saline contrast echocardiography (to characterize intracardiac shunting) and multidisciplinary deliberation, may offer insights into structural cardiac pathophysiologic effects and transplant-related hemodynamic changes that impact new grafts. At the same time, active and effective monitoring and other measures should be taken to maintain hemodynamic stability in the perioperative period, avoid entry of bubbles into the circulation, and ease congestion in newly grafted livers. Such efforts are crucial for transplantation success and graft survival.

7.
Neurochem Int ; 161: 105435, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36273706

RESUMO

Nicotinamide adenine dinucleotide (NAD+) is an omnipresent metabolite that participates in redox reactions. Multiple NAD+-consuming enzymes are implicated in numerous biological processes, including transcription, signaling, and cell survival. Multiple pieces of evidence have demonstrated that NAD+-consuming enzymes, including poly(ADP-ribose) polymerases (PARPs), sirtuins (SIRTs), and sterile alpha and TIR motif-containing 1 (SARM1), play major roles in peripheral neuropathic pain of various etiologies. These NAD+ consumers primarily participate in peripheral neuropathic pain via mechanisms such as mitochondrial dysfunction, oxidative stress, and inflammation. Furthermore, NAD+ synthase and nicotinamide phosphoribosyltransferase (NAMPT) have recently been found to contribute to the regulation of pain. Here, we review the evidence indicating the involvement of NAD+ metabolism in the pathological mechanisms of peripheral neuropathic pain. Advanced understanding of the molecular and cellular mechanisms associated with NAD+ in peripheral neuropathic pain will facilitate the development of novel treatment options for diverse types of peripheral neuropathic pain.


Assuntos
Neuralgia , Sirtuínas , Humanos , NAD/metabolismo , Sirtuínas/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Oxirredução
8.
Cell Death Discov ; 8(1): 415, 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36216824

RESUMO

Embryo adhesion is a very important step in the embryo implantation process. Homeobox A10 (HOXA10), a key transcriptional factor of endometrial receptivity, is indispensable for embryo adhesion. However, how to control the activation status of HOXA10 remains elusive. Here, we found that Mitogen-activated protein kinase kinase kinase 4 (MEKK4) was associated with HOXA10 and directly phosphorylated HOXA10 at threonine 362. This MEKK4-mediated phosphorylation enhanced HOXA10-mediated transcriptional responses and adhesion between the embryo and endometrial epithelium. Specific deletion or kinase inactivation of MEKK4 in endometrial epithelial cells attenuates adhesion between embryo and epithelium. Therefore, the identification of MEKK4 as a novel physiological positive regulator of HOXA10 activation provides mechanistic insights to improve embryo implantation success. Moreover, when Thr362 was mutated to alanine (T362A) to mimic its dephosphorylation, the protein stability and transcriptional regulation of HOXA10 were decreased. In addition, HOXA10 -promoted embryo adhesion was weakened after the mutation of Thr362, suggesting that the phosphorylation of HOXA10 at this site may be a new indicator for evaluating endometrial receptivity and judging the 'implantation window'.

9.
Front Cell Dev Biol ; 10: 954214, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120577

RESUMO

Background: N6-methyladenosine (m6A) modification is a dynamic and reversible post-transcriptional RNA modification prevalent in eukaryotic cells. YT521-B homology domain family 2 (YTHDF2) has been identified as a member of m6A reader protein involving in many vital biological processes, whereas its role and functional mechanisms in cancers remain unclear. Methods: Bioinformatics analyses were performed on multiple databases including GTEx, TCGA, GEO and Cbioportal to explore the connection between YTHDF2 expression and its genomic changes including tumor mutation burden, microsatellite instability and mismatch repair in 33 different cancer types. We also investigated the association of YTHDF2 expression with prognosis, immune infiltration, tumor microenvironment, immune checkpoints and chemokines. Besides, the correlation of YTHDF2 expression with copy number variation and promoter methylation was also studied in tumors compared with normal tissues. At last, we analyzed the protein-protein interacting network and related genes of YTHDF2 to enrich its potential functional mechanism in tumor development and progression. Real-time qPCR was used to verify the expression of YTHDF2-related genes in colorectal cancer cells, and immunohistochemical staining was adopted to verify immune infiltration in tissue sections from 51 hepatocellular carcinoma patients. Results: YTHDF2 was overexpressed in a majority of tumor types and associated with their poor overall survival, progression-free interval, and disease-specific survival. The correlation of YTHDF2 expression with tumor mutation burden, microsatellite instability and mismatch repair was also detected in most of the tumor types. Moreover, YTHDF2 might participate in the immune regulation through influencing the expression of immune checkpoint genes and the infiltration of immunocytes in tumor microenvironment. Notably, we demonstrated a positive correlation between YTHDF2 expression and the infiltration of CD8+ T cells and macrophages in many tumors, and it was verified in 51 clinic hepatocellular carcinoma tissues. In addition, the involvement of YTHDF2 in "Spliceosome" and "RNA degradation" were two potential functional mechanisms underlying its influence on tumor progression. The regulation of YTHDF2 on predicted genes has been verified in CRC cells. Conclusion: YTHDF2 might be a new therapeutic target and a potential biomarker of cancer immune evasion and poor prognosis.

10.
Biomater Adv ; 138: 212876, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35913233

RESUMO

Mitochondrial damage is one of the primary causes of neuronal cell death in Parkinson's disease (PD). In PD patients, the mitochondrial damage can be repaired or irreversible. Therefore, mitochondrial damage repair becomes a promising strategy for PD treatment. In this research, hyaluronic acid nanoparticles (HA-NPs) of different molecular weights are used to protect the mitochondria and salvage the mild and limited damage in mitochondria. The HA-NPs with 2190 k Dalton (kDa) HA can improve the mitochondrial function of SH-SY5Y cells and PTEN induced putative kinase 1 (PINK1) knockout mouse embryo fibroblast (MEF) cells. In cases of irreversible damage, NPs with ubiquitin specific peptidase 30 (USP30) siRNA are used to promote mitophagy. Meanwhile, by adding PINK1 antibodies, the NPs can selectively target the irreversibly damaged mitochondria, preventing the excessive clearance of healthy mitochondria.


Assuntos
Nanopartículas , Neuroblastoma , Doença de Parkinson , Animais , Humanos , Camundongos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Nanopartículas/uso terapêutico , Neuroblastoma/metabolismo , Doença de Parkinson/tratamento farmacológico , Proteínas Quinases/genética , Tioléster Hidrolases/metabolismo , Ubiquitina-Proteína Ligases/genética
11.
Front Pharmacol ; 13: 938979, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935847

RESUMO

Itaconate plays a prominent role in anti-inflammatory effects and has gradually been ushered as a promising drug candidate for treating inflammatory diseases. However, its significance and underlying mechanism for inflammatory pain remain unexplored. In the current study, we investigated the effects and mechanisms of Dimethyl Itaconate (DI, a derivative of itaconate) on Complete Freund's adjuvant (CFA)-induced inflammatory pain in a rodent model. Here, we demonstrated that DI significantly reduced mechanical allodynia and thermal hyperalgesia. The DI-attenuated neuroinflammation was evident with the amelioration of infiltrative macrophages in peripheral sites of the hind paw and the dorsal root ganglion. Concurrently, DI hindered the central microglia activation in the spinal cord. Mechanistically, DI inhibited the expression of pro-inflammatory factors interleukin (IL)-1ß and tumor necrosis factor alpha (TNF-α) and upregulated anti-inflammatory factor IL-10. The analgesic mechanism of DI was related to the downregulation of the nod-like receptor protein 3 (NLRP3) inflammasome complex and IL-1ß secretion. This study suggested possible novel evidence for prospective itaconate utilization in the management of inflammatory pain.

12.
Int J Mol Sci ; 23(15)2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35955410

RESUMO

The bioactive lipid lysophosphatidylcholine (LPC), a major phospholipid component of oxidized low-density lipoprotein (Ox-LDL), originates from the cleavage of phosphatidylcholine by phospholipase A2 (PLA2) and is catabolized to other substances by different enzymatic pathways. LPC exerts pleiotropic effects mediated by its receptors, G protein-coupled signaling receptors, Toll-like receptors, and ion channels to activate several second messengers. Lysophosphatidylcholine (LPC) is increasingly considered a key marker/factor positively in pathological states, especially inflammation and atherosclerosis development. Current studies have indicated that the injury of nervous tissues promotes oxidative stress and lipid peroxidation, as well as excessive accumulation of LPC, enhancing the membrane hyperexcitability to induce chronic pain, which may be recognized as one of the hallmarks of chronic pain. However, findings from lipidomic studies of LPC have been lacking in the context of chronic pain. In this review, we focus in some detail on LPC sources, biochemical pathways, and the signal-transduction system. Moreover, we outline the detection methods of LPC for accurate analysis of each individual LPC species and reveal the pathophysiological implication of LPC in chronic pain, which makes it an interesting target for biomarkers and the development of medicine regarding chronic pain.


Assuntos
Aterosclerose , Dor Crônica , Aterosclerose/metabolismo , Dor Crônica/tratamento farmacológico , Humanos , Lipoproteínas LDL/metabolismo , Lisofosfatidilcolinas/metabolismo , Fosfolipases A2/metabolismo , Receptores Acoplados a Proteínas G , Transdução de Sinais
13.
Transl Androl Urol ; 11(6): 750-760, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35812194

RESUMO

Background: Homeodomain (HD) proteins contain an evolutionarily conserved helix-turn-helix (HTH) DNA-binding motif and act as transcription factors to control gene expression. A previous study showed that the HD gene Homez is highly enriched in adult testes. However, the role of HOMEZ in spermatogenesis and male fertility remains unknown. Methods: Using CRISPR/Cas9 technology, Homez mutant mice were generated and performed histological, immunofluorescence, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot and mating assays to analyze the phenotype of Homez mutants. Results: Molecular phylogenetic analyses indicated that the HOMEZ is evolutionarily conserved among mammalian species. qRT-PCR and Western blot analyses showed that Homez is highly expressed in the testis, with a relatively increased expression trend during spermatogenesis. Homez mutant males were viable and showed no differences in body and testis weight compared to their wild-type. In addition, mating between Homez mutant males and wild-type females produced normal litter sizes. Moreover, histopathology detected complete spermatogenesis in the seminiferous tubules and mature spermatozoa in the epididymides from Homez knockout males. Furthermore, significantly increased transcription of three Zhx genes were found in Homez mutatnt testes compared with wild-type testes. Conclusions: Homez knockout mice are fertile and are not essential for germ cell development. These findings could prevent unnecessary duplicative work by other groups.

14.
Biomolecules ; 12(6)2022 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-35740951

RESUMO

Since no definitive cure for COVID-19 is available so far, one of the challenges against the disease is understanding the clinical features and the laboratory inflammatory markers that can differentiate among different severity grades of the disease. The aim of the present study is a comprehensive and longitudinal evaluation of SCD14-ST and other new inflammatory markers, as well as cytokine storm molecules and current inflammatory parameters, in order to define a panel of biomarkers that could be useful for a better prognostic prediction of COVID-19 mortality. SCD14-ST, as well as the inflammatory markers IL-6, IL-10, SuPAR and sRAGE, were measured in plasma-EDTA of ICU COVID-19 positive patients. In this longitudinal study, SCD14-ST resulted significantly higher in patients who eventually died compared to those who were discharged from the ICU. The results suggest that the new infection biomarker SCD14-ST, in addition to new generation inflammatory biomarkers, such as SuPAR, sRAGE and the cytokines IL-6 and IL-10, can be a useful prognostic tool associated with canonical inflammatory parameters, such as CRP, to predict SARS-CoV-2 outcome in ICU patients.


Assuntos
COVID-19 , Receptores de Lipopolissacarídeos , Biomarcadores , COVID-19/diagnóstico , Humanos , Interleucina-10 , Interleucina-6 , Estudos Longitudinais , Receptores de Ativador de Plasminogênio Tipo Uroquinase , SARS-CoV-2
15.
BMC Anesthesiol ; 22(1): 194, 2022 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-35733086

RESUMO

BACKGROUND: Cough caused by endotracheal tube (ETT) placement is ubiquitous and correlates with adverse outcomes. Remifentanil administration via target-controlled infusion (TCI) is one of the cough prevention measures used during recovery. In a pilot study, lidocaine administered via the perforated outer cuff of a dual-cuff endotracheal tube was also found to prevent cough due to ETT placement. We therefore compared these two cough prevention approaches during recovery after thyroidectomy in a single-centre, double-blind, randomised study conducted in China during the period from 09/10/2020 to 30/04/2021. METHODS: Ninety-eight female patients aged 18-65 years with American Society of Anaesthesiologists Physical Status scores of I and II were scheduled to undergo thyroidectomy. The ETT contained an internal cuff covered by a perforated outer cuff to allow for lidocaine delivery. Patients were randomised to receive either 4 ml of saline solution (Group R, n = 49) or 4 ml of 2% lidocaine in the outer cuff (Group L, n = 49) at the beginning of skin suturing. Remifentanil (2 ng/ml) was maintained in Group R until extubation, while remifentanil was maintained in Group L until the end of skin suturing. The primary outcome was cough during patient transfer, at 1 min before extubation, and at extubation. The secondary outcomes were haemodynamics and other recovery parameters. RESULTS: Primary outcomes were compared between remifentanil vs. lidocaine application, namely, the incidence of cough during patient transfer (0% in Group R vs. 0% in Group L), at 1 min before extubation (22.45% in Group R vs. 4.08% in Group L; P = 0.015), and at extubation (61.22% in Group R vs. 20.41% in Group L; P < 0.001). Compared with remifentanil, lidocaine more effectively decreased heart rate elevation and hypoxemia at 5 min after extubation, the spontaneous respiration recovery time, the extubation time, the duration of post-anaesthesia care unit (PACU) stay, Richmond Agitation-Sedation Scale scores in the agitated range and Critical-Care Pain Observation Tool scores. CONCLUSION: Lidocaine administered via the perforated outer cuff of the ETT significantly improved recovery from general anaesthesia compared to remifentanil in female patients after thyroidectomy. TRIAL REGISTRATION: Chinese Clinical Trial Registry (No. ChiCTR2000038653), registered on 27/09/2020.


Assuntos
Lidocaína , Tireoidectomia , Anestesia Geral/efeitos adversos , Tosse/etiologia , Método Duplo-Cego , Feminino , Humanos , Intubação Intratraqueal/efeitos adversos , Projetos Piloto , Remifentanil/uso terapêutico , Tireoidectomia/efeitos adversos
16.
Front Immunol ; 13: 896745, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35757759

RESUMO

Periodontitis is an infectious oral disease, which leads to the destruction of periodontal tissues and tooth loss. Although the treatment of periodontitis has improved recently, the effective treatment of periodontitis and the periodontitis-affected periodontal tissues is still a challenge. Therefore, it is urgent to explore new therapeutic strategies for periodontitis. Natural products show anti-microbial, anti-inflammatory, anti-oxidant and bone protective effects to periodontitis and most of these natural products are safe and cost-effective. Among these, the plant-derived exosome-like nanoparticles (PELNs), a type of natural nanocarriers repleted with lipids, proteins, RNAs, and other active molecules, show the ability to enter mammalian cells and regulate cellular activities. Reports from the literature indicate the great potential of PELNs in the regulation of immune functions, inflammation, microbiome, and tissue regeneration. Moreover, PELNs can also be used as drug carriers to enhance drug stability and cellular uptake in vivo. Since regulation of immune function, inflammation, microbiome, and tissue regeneration are the key phenomena usually targeted during periodontitis treatment, the PELNs hold the promising potential for periodontitis treatment. This review summarizes the recent advances in PELNs-related research that are related to the treatment of periodontitis and regeneration of periodontitis-destructed tissues and the underlying mechanisms. We also discuss the existing challenges and prospects of the application of PELNs-based therapeutic approaches for periodontitis treatment.


Assuntos
Produtos Biológicos , Exossomos , Nanopartículas , Periodontite , Animais , Anti-Inflamatórios/uso terapêutico , Produtos Biológicos/uso terapêutico , Exossomos/metabolismo , Inflamação/tratamento farmacológico , Mamíferos , Nanopartículas/uso terapêutico , Periodontite/tratamento farmacológico
17.
Cell Mol Life Sci ; 79(6): 286, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534740

RESUMO

Endocytosis is controlled by a well-orchestrated molecular machinery, where the individual players as well as their precise interactions are not fully understood. We now show that syndapin I/PACSIN 1 is expressed in pancreatic ß cells and that its knockdown abrogates ß cell endocytosis leading to disturbed plasma membrane protein homeostasis, as exemplified by an elevated density of L-type Ca2+ channels. Intriguingly, inositol hexakisphosphate (InsP6) activates casein kinase 2 (CK2) that phosphorylates syndapin I/PACSIN 1, thereby promoting interactions between syndapin I/PACSIN 1 and neural Wiskott-Aldrich syndrome protein (N-WASP) and driving ß cell endocytosis. Dominant-negative interference with endogenous syndapin I/PACSIN 1 protein complexes, by overexpression of the syndapin I/PACSIN 1 SH3 domain, decreases InsP6-stimulated endocytosis. InsP6 thus promotes syndapin I/PACSIN 1 priming by CK2-dependent phosphorylation, which endows the syndapin I/PACSIN 1 SH3 domain with the capability to interact with the endocytic machinery and thereby initiate endocytosis, as exemplified in ß cells.


Assuntos
Proteínas do Citoesqueleto , Ácido Fítico , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proteínas do Citoesqueleto/metabolismo , Endocitose/fisiologia , Fosforilação
18.
PeerJ Comput Sci ; 8: e982, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35634126

RESUMO

Time series appear in many scientific fields and are an important type of data. The use of time series analysis techniques is an essential means of discovering the knowledge hidden in this type of data. In recent years, many scholars have achieved fruitful results in the study of time series. A statistical analysis of 120,000 literatures published between 2017 and 2021 reveals that the topical research about time series is mostly focused on their classification and prediction. Therefore, in this study, we focus on analyzing the technical development routes of time series classification and prediction algorithms. 87 literatures with high relevance and high citation are selected for analysis, aiming to provide a more comprehensive reference base for interested researchers. For time series classification, it is divided into supervised methods, semi-supervised methods, and early classification of time series, which are key extensions of time series classification tasks. For time series prediction, from classical statistical methods, to neural network methods, and then to fuzzy modeling and transfer learning methods, the performance and applications of these different methods are discussed. We hope this article can help aid the understanding of the current development status and discover possible future research directions, such as exploring interpretability of time series analysis and online learning modeling.

19.
Cell Transplant ; 31: 9636897211066508, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35156411

RESUMO

We exploited the anterior chamber of the eye (ACE) of immunodeficient mice as an ectopic site for both transplantation and microimaging of engineered surrogate islets from human induced pluripotent stem cells (hiPSC-SIs). These islets contained a majority of insulin-expressing cells, positive or negative for PDX1 and NKX6.1, and a minority of glucagon- or somatostatin-positive cells. Single, non-aggregated hiPSC-SIs were satisfactorily engrafted onto the iris. They underwent gradual vascularization and progressively increased their light scattering signals, reflecting the abundance of zinc-insulin crystal packaged inside mature insulin secretory granules. Intracameral hiPSC-SIs retrieved from recipients showed enhanced insulin immunofluorescence in correlation with the parallel increase in overall vascularization and light backscattering during the post-transplantation period. This approach enables longitudinal, nondestructive and intravital microimaging of cell fates, engraftment, vascularization and mature insulin secretory granules of single hiPSC-SI grafts, and may offer a feasible and reliable means to screen compounds for promoting in vivo hiPSC-SI maturation.


Assuntos
Células-Tronco Pluripotentes Induzidas , Células Secretoras de Insulina , Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas , Animais , Humanos , Insulina , Camundongos
20.
Neurochem Int ; 154: 105296, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35121012

RESUMO

The metabolite itaconate has both anti-inflammatory and immunomodulatory effects. However, its influence on chronic pain is unclear. Here, we demonstrated that intraperitoneal injection of the itaconate derivative dimethyl itaconate (DI) alleviated chronic pain symptoms, such as allodynia and hyperalgesia, in spinal nerve ligation (SNL) and inflammatory pain models. Moreover, intraperitoneal DI reduced the secretion of inflammatory cytokines (i.e., interleukin-1ß, tumour necrosis factor-alpha) in dorsal root ganglion (DRG), spinal cord and hind paw tissues, suppressed the activation of macrophages in the DRG and glial cells in the spinal dorsal horn and decreased the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the DRG and spinal cord. DI boosted nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) levels in the DRG and spinal cord of SNL mice. Intraperitoneal administration of the Nrf2 inhibitor ML385 abolished the analgesic effect of DI and decreased the expression of Nrf2 in the DRG and spinal cord. Similarly, administration of DI potently reversed the lipopolysaccharide (LPS)-induced inflammatory effect in microglia. Reduction of endogenous itaconate levels by pretreatment with immune-responsive gene 1 (IRG1) siRNA blocked Nrf2 expression, which impaired the analgesic and anti-inflammatory effects of DI in vitro. Therefore, our findings revealed for the first time that intraperitoneal DI elicited anti-inflammatory effect and sustained chronic pain relief, which may be regarded as a promising therapeutic agent for chronic pain treatment.


Assuntos
Dor Crônica , Neuralgia , Animais , Dor Crônica/tratamento farmacológico , Gânglios Espinais/metabolismo , Hiperalgesia/metabolismo , Camundongos , Neuralgia/metabolismo , Doenças Neuroinflamatórias , Ratos , Ratos Sprague-Dawley , Medula Espinal/metabolismo , Corno Dorsal da Medula Espinal , Succinatos
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