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1.
Cell Signal ; 124: 111453, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39366533

RESUMO

BACKGROUND: Tumor-associated macrophages (TAMs) play an important role in the recurrence and progression of clear cell renal cell carcinoma (ccRCC). However, the specified mechanism has not been elucidated. METHODS: Single-cell and transcriptome analysis were applied to characterize the heterogeneity of TAMs. SCENIC would infer regulators of different subsets of TAMs. The CellChat algorithm was used to infer macrophage-tumor interaction networks, whereas pseudo-time traces were used to parse cell evolution and dynamics. RESULTS: In this study, single-cell transcriptomic data of ccRCC were analyzed. Notably, the macrophages were clustered to select the cluster with a tendency toward M2-type TAM, which has an impact on the occurrence and metastasis of ccRCC. This macrophage cluster was defined as "TAM2". And this study revealed that TCF7L2 as a potential transcription factor regulating TAM2 transcriptional heterogeneity and differentiation. Pseudotime traces showed TCF7L2 trajectories during TAM2 cell cluster development. In addition, the results of cell interaction showed that TAM2 had the highest number and strength of interactions with cancer cells and endothelial cells. In vitro experiments, this study found that TCF7L2 was highly expressed in TAMs and promoted the polarization of macrophages to M2-type macrophages. And then overexpression of TCF7L2 in macrophages markedly promoted ccRCC invasion and proliferation. CONCLUSION: TCF7L2 could play a key role in the progression of ccRCC via enhancing TAMs recruitment and M2-type polarization.

2.
Zhonghua Nan Ke Xue ; 30(5): 450-455, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-39210496

RESUMO

The incidence of male infertility has been increasing year by year, and one of the major causes is testicular spermatogenic epithelial injury, which affects the spermatogenic function of the testis. Ferroptosis is a novel mode of cell death and plays an important role in testicular cell injury. Some traditional Chinese medicines can intervene in the progression of testicular injury by regulating the ferroptosis pathway in testicular spermatogenic epithelia. This paper focuses on the effect of traditional Chinese drugs in regulating the ferroptosis pathway in testicular cells, and summarizes the advances in the studies of traditional Chinese medicines in the treatment of testicular spermatogenic epithelial injury, aiming to provide a theoretical basis for the selection of relevant medicines and their clinical application.


Assuntos
Medicamentos de Ervas Chinesas , Ferroptose , Infertilidade Masculina , Medicina Tradicional Chinesa , Espermatogênese , Ferroptose/efeitos dos fármacos , Masculino , Humanos , Medicina Tradicional Chinesa/métodos , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Infertilidade Masculina/tratamento farmacológico , Infertilidade Masculina/etiologia , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais
3.
Arch Toxicol ; 98(11): 3763-3775, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39192019

RESUMO

Chlorfenapyr is a novel broad-spectrum insecticide derived from natural pyrrole derivatives produced by Streptomyces spp. It acts as a pro-insecticide and is metabolically converted to the active metabolite, tralopyril. Chlorfenapyr poisoning is known for its delayed neurological symptoms and high mortality. Unfortunately, information on the toxicokinetics, metabolism and tissue distribution of chlorfenapyr and tralopyril is still lacking. In this study, the metabolic profile, toxicokinetics and tissue distribution of chlorfenapyr and tralopyril after oral administration at a toxic dose in mice were investigated. Twenty metabolites were identified in plasma, urine and feces, which were mainly formed by dealkylation, oxidative dechlorination and reductive dechlorination. Toxicokinetic results showed that chlorfenapyr was rapidly converted to tralopyril after administration, and the in vivo half-life (t1/2), area under the curve (AUC) and peak concentration (Cmax) values of tralopyril were significantly higher than those of chlorfenapyr (P < 0.05). Tissue distribution experiments confirmed that the metabolite tralopyril had a longer half-life, a lower clearance and a wide distribution in different organs and tissues compared to chlorfenapyr. It was also able to cross the blood-brain barrier, suggesting a potential association with brain lesions. In addition, a sensitive and rapid LC-MS/MS analytical method was established for the detection of chlorfenapyr and tralopyril. In conclusion, this study provided valuable metabolic, toxicokinetic and tissue distribution information, contributing to future risk assessment and forensic identification in cases of chlorfenapyr poisoning. We recommend considering the assessment of tralopyril levels, which may be of greater therapeutic importance in the management of chlorfenapyr poisoning.


Assuntos
Inseticidas , Piretrinas , Toxicocinética , Animais , Distribuição Tecidual , Inseticidas/toxicidade , Inseticidas/farmacocinética , Camundongos , Masculino , Piretrinas/farmacocinética , Piretrinas/toxicidade , Piretrinas/metabolismo , Administração Oral , Meia-Vida , Área Sob a Curva , Fezes/química
4.
Artigo em Inglês | MEDLINE | ID: mdl-38990461

RESUMO

Cardiac fibrosis following myocardial infarction (MI) seriously affects the prognosis and survival rate of patients. This study aimed to determine the effect and regulation mechanism of the dedicator of cytokinesis 2 (DOCK2) during this process. Experiments were carried out in mice in vivo, and in Ang II treated cardiac fibroblasts (CFs) in vitro. DOCK2 was increased in mouse myocardial tissues after MI and Ang II-treated CFs. In MI mice, DOCK2 silencing improved cardiac function, and ameliorated cardiac fibrosis. DOCK2 knockdown suppressed the activation of CFs and decreased the expression of α-SMA, collagen I, and collagen III. Suppression of DOCK2 mitigated Ang II induced migration of CFs. DOCK2 inhibition reduced the activity of the PI3K/Akt and Wnt/ß-catenin pathways, while this change could be reversed by the pathway activators, SC79 and SKL2001. In summary, DOCK2 suppression improves cardiac dysfunction and attenuates cardiac fibrosis after MI via attenuating PI3K/Akt and Wnt/ß-catenin pathways.

6.
Adv Sci (Weinh) ; 11(25): e2401623, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38639391

RESUMO

Proteolysis-targeting chimeras (PROTACs) have emerged as a promising strategy for targeted protein degradation and drug discovery. To overcome the inherent limitations of conventional PROTACs, an innovative drugtamer-PROTAC conjugation approach is developed to enhance tumor targeting and antitumor potency. Specifically, a smart prodrug is designed by conjugating "drugtamer" to a nicotinamide phosphoribosyltransferase (NAMPT) PROTAC using a tumor microenvironment responsible linker. The "drugtamer" consists of fluorouridine nucleotide and DNA-like oligomer. Compared to NAMPT PROTAC and the combination of PROTAC + fluorouracil, the designed prodrug AS-2F-NP demonstrates superior tumor targeting, efficient cellular uptake, improved in vivo potency and reduced side effects. This study provides a promising strategy for the precise delivery of PROTAC and synergistic antitumor agents.


Assuntos
Antineoplásicos , Animais , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Humanos , Linhagem Celular Tumoral , Proteólise/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Pró-Fármacos/farmacologia , Pró-Fármacos/química , Modelos Animais de Doenças , Nicotinamida Fosforribosiltransferase/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Sinergismo Farmacológico
7.
Mol Nutr Food Res ; 68(8): e2300797, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38549456

RESUMO

SCOPE: l-Theanine (l-Thea) is an amino acid which is naturally present in tea leaves. It has been associated with possible health advantages, including obesity prevention, but the underlying molecular mechanisms have not been elucidated. METHODS AND RESULTS: A multiomics approach is utilized to examine the mechanism by which l-Thea exerts its antiobesity effects. This study reveals that l-Thea administration significantly ameliorates high-fat diet (HFD)-induced obesity in rats by improving body weight and hyperlipidemia. l-Thea mitigates HFD-induced inflammation and reverses hepatic and colonic damage, and intestinal barrier. This research verifies that the preventive effect of l-Thea on obesity in rats induced by an HFD with colitis is accomplished by suppressing the phosphorylation of important proteins in the NF-κB/mitogen-activated protein kinase (MAPK) pathways. Metabolome analysis reveals that l-Thea regulates HFD-induced metabolic disorders, specifically through modulation of steroid hormone biosynthesis. Microbiome analysis reveals that l-Thea mitigates HFD-induced dysbiosis by increasing the relative abundance of obesity-associated probiotic bacteria, including Blautia coccoides and Lactobacillus murinus, while simultaneously suppressing the abundance of pathogenic bacteria. CONCLUSIONS: l-Thea alleviates colitis generated by an HFD by restoring the integrity of the intestinal barrier, suppressing inflammation through regulation of MAPK/NF-κB signaling pathways, and enhancing microbial metabolism in colon.


Assuntos
Colo , Dieta Hiperlipídica , Obesidade , Animais , Masculino , Ratos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Colo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Disbiose , Microbioma Gastrointestinal/efeitos dos fármacos , Glutamatos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
8.
Front Genet ; 15: 1353438, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38456015

RESUMO

Background: Previous observational studies have investigated the association between sleep-related traits and male fertility; however, conclusive evidence of a causal connection is lacking. This study aimed to explore the causal relationship between sleep and male fertility using Mendelian randomisation. Methods: Eight sleep-related traits (chronotype, sleep duration, insomnia, snoring, dozing, daytime nap, oversleeping, and undersleeping) and three descriptors representing male fertility (male infertility, abnormal sperm, and bioavailable testosterone levels) were selected from published Genome-Wide Association Studies. The causal relationship between sleep-related traits and male fertility was evaluated using multiple methods, including inverse variance weighting (IVW), weighted median, Mendelian randomisation-Egger, weighted model, and simple model through two-sample Mendelian randomisation analysis. Mendelian randomisation-Egger regression was used to assess pleiotropy, Cochrane's Q test was employed to detect heterogeneity, and a leave-one-out sensitivity analysis was conducted. Results: Genetically-predicted chronotype (IVW,OR = 1.07; 95%CL = 1.04-1.12; p = 0.0002) was suggestively associated with bioavailable testosterone levels. However, using the IVW method, we found no evidence of a causal association between other sleep traits and male fertility. Conclusion: This study found that chronotype affects testosterone secretion levels. However, further studies are needed to explain this mechanism.

9.
Dalton Trans ; 53(9): 4119-4126, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38315146

RESUMO

To bring about a revolution in energy storage through Li-ion batteries, it is crucial to develop a scalable preparation method for Si-based composite anodes. However, the severe volume expansion and poor ionic transport properties of Si-based composites present significant challenges. Previous research focused on SiO and nano Si/C composites to address these issues. In this study, mechanical milling was used to introduce a SiOx layer onto the surface of Si by mixing Si and SiO2 in a 1 : 1 mass ratio. The resulting Si+SiO2 composites (denoted as SS50) exhibited an initial coulombic efficiency (ICE) of 73.5% and high rate performance. To further stabilize the overall structure, kerosene was introduced as a carbon source precursor to generate a coating layer. The resulting multiphase composite structure (SiOx+SiO2+C), designated as SS50-900C, demonstrated a capacity retention of 79.5% over 280 cycles at its capacity of 487 mA h g-1. These results suggest that a cost-effective mechanical ball milling refinement of Si+SiO2 and a gas-phase encapsulation process can significantly improve the electrochemical performance of Si-based composites.

10.
J Nanobiotechnology ; 22(1): 33, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238760

RESUMO

BACKGROUND: The complex etiology and pathogenesis underlying Chronic Non-Bacterial Prostatitis (CNP), coupled with the existence of a Blood Prostate Barrier (BPB), contribute to a lack of specificity and poor penetration of most drugs. Emodin (EMO), a potential natural compound for CNP treatment, exhibits commendable anti-inflammatory, anti-oxidant, and anti-fibrosis properties but suffers from the same problems as other drugs. METHODS: By exploiting the recognition properties of lactoferrin (LF) receptors that target intestinal epithelial cells (NCM-460) and prostate epithelial cells (RWPE-1), a pathway is established for the transrectal absorption of EMO to effectively reach the prostate. Additionally, hyaluronic acid (HA) is employed, recognizing CD44 receptors which target macrophages within the inflamed prostate. This interaction facilitates the intraprostatic delivery of EMO, leading to its pronounced anti-inflammatory effects. A thermosensitive hydrogel (CS-Gel) prepared from chitosan (CS) and ß-glycerophosphate disodium salt (ß-GP) was used for rectal drug delivery with strong adhesion to achieve effective drug retention and sustained slow release. Thus, we developed a triple-targeted nanoparticle (NPs)/thermosensitive hydrogel (Gel) rectal drug delivery system. In this process, LF, with its positive charge, was utilized to load EMO through dialysis, producing LF@EMO-NPs. Subsequently, HA was employed to encapsulate EMO-loaded LF nanoparticles via electrostatic adsorption, yielding HA/LF@EMO-NPs. Finally, HA/LF@EMO-NPs lyophilized powder was added to CS-Gel (HA/LF@EMO-NPs Gel). RESULTS: Cellular assays indicated that NCM-460 and RWPE-1 cells showed high uptake of both LF@EMO-NPs and HA/LF@EMO-NPs, while Raw 264.7 cells exhibited substantial uptake of HA/LF@EMO-NPs. For LPS-induced Raw 264.7 cells, HA/LF@EMO-NPs can reduce the inflammatory responses by modulating TLR4/NF-κB signaling pathways. Tissue imaging corroborated the capacity of HA/LF-modified formulations to breach the BPB, accumulating within the gland's lumen. Animal experiments showed that rectal administration of HA/LF@EMO-NPs Gel significantly reduced inflammatory cytokine expression, oxidative stress levels and fibrosis in the CNP rats, in addition to exerting anti-inflammatory effects by inhibiting the NF-κB signaling pathway without obvious toxicity. CONCLUSION: This triple-targeted NPs/Gel rectal delivery system with slow-release anti-inflammatory, anti-oxidant, and anti-fibrosis properties shows great potential for the effective treatment of CNP.


Assuntos
Quitosana , Emodina , Nanopartículas , Prostatite , Humanos , Masculino , Ratos , Animais , Hidrogéis , Emodina/farmacologia , Emodina/uso terapêutico , Prostatite/tratamento farmacológico , Antioxidantes , NF-kappa B , Sistemas de Liberação de Medicamentos/métodos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Portadores de Fármacos
11.
Reprod Sci ; 31(1): 222-238, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37679557

RESUMO

As a rare disease leading to male infertility, idiopathic hypogonadotropic hypogonadism (IHH) has strong heterogeneity of clinical phenotype and gene mutation. At present, there is no effective diagnosis and treatment method for this disease. This study is to explore the possible new pathogenic gene of idiopathic hypogonadotrophic hypogonadism and the pathological mechanism affecting its occurrence. We performed a whole-exome sequencing on 9 patients with normosmic idiopathic hypogonadotropic hypogonadism (nIHH), 19 varicocele patients with asthenospermia, oligospermia, or azoospermia, 5 patients with simple nonobstructive azoospermia, and 13 normal healthy adult males and carried out comparative analysis, channel analysis, etc. After preliminary sequencing screening, 309-431 genes harbouring variants, including SNPs and indels, were predicted to be harmful per single patient in each group. In genetic variations of nIHH patients' analysis, variants were detected in 10 loci and nine genes in nine patients. And in co-analysis of the three patient groups, nine nIHH patients, 19 VC patients, and five SN patients shared 116 variants, with 28 variant-harbouring genes detected in five or more patients. We found that the NEFH, CCDC177, and PCLO genes and the Gene Ontology pathways GO:0051301: cell division and GO:0090066: regulation of anatomical structure size may be key factors in the pathogenic mechanism of IHH. Our results suggest that the pathogenic mechanism of IHH is not limited to the central nervous system effects of GnRH but may involve other heterogeneous pathogenic genetic variants that affect peripheral organs.


Assuntos
Azoospermia , Hipogonadismo , Varicocele , Adulto , Humanos , Masculino , Azoospermia/genética , Sequenciamento do Exoma , Varicocele/genética , Hipogonadismo/genética , Hipogonadismo/diagnóstico , Mutação
12.
Int J Impot Res ; 36(2): 110-117, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37198341

RESUMO

This study aimed to summarize the characteristics of the top 100 most-cited publications on Peyronie's disease (PD) research and to analyse past and current research hotspots and trends. The SCI-E database of the Web of Science Core Collection (WoSCC) provided us with the top 100 most-cited publications in PD research, from which we took the following information: general trend of publication, year of publication, nation/region, institution, journal, author, and keywords. VOSviewer (version 1.6.18) and Excel (version 2016) were used for information analysis. Through a standardized search, we ultimately found 1019 papers in the field of PD research, from which we extracted the 100 articles that had received the highest citations. The articles were published between 1949 and 2016. The United States is a major contributor to PD research (n = 67). The University of California, Los Angeles, was the institution with the largest number of articles (n = 11). These articles were published in 16 journals, with the largest number appearing in the Journal of Urology (n = 47). The author with the most articles was Levine LA (n = 9). Gelbard MK's articles had the highest citation frequency (n = 1158). Erectile dysfunction (n = 19) was the keyword with the highest frequency, indicating that PD-related erectile dysfunction was the leading focus of research in this field. Most of the keywords that have appeared in the past decade are related to the clinical treatment of PD. Therefore, we believe that improving patients' erectile function to the greatest extent in clinical treatment is the frontier and hot spot of future research.


Assuntos
Disfunção Erétil , Induração Peniana , Urologia , Masculino , Humanos , Bibliometria , Bases de Dados Factuais
13.
Reprod Sci ; 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057530

RESUMO

BACKGROUND: Obesity, insulin resistance, and hyperandrogenemia are commonly seen in women with polycystic ovary syndrome (PCOS), and these three conditions form a vicious cycle leading to reproductive and metabolic abnormalities. Metformin improves the symptoms of PCOS by increasing insulin sensitivity but is not therapeutically optimal. Recent studies have reported that sodium-glucose co-transporter protein receptor inhibitors improve insulin resistance and reduce the weight of patients with PCOS. We performed a meta-analysis to assess the influence of sodium-glucose co-transporter protein-2 (SGLT2) inhibitors on anthropometric, glycolipid metabolism and reproductive outcomes after therapy of overweight/obese women with PCOS. METHODS: We searched the relevant literature published up to April 2023. Information on the effect of SGLT2 inhibitors on overweight/obese patients with PCOS was extracted independently by two reviewers. Review Manager 5.3 was used for meta-analysis. RESULTS: Five randomized controlled trials that met our criteria were retrieved. Our meta-analysis demonstrated that in overweight/obese patients with PCOS, SGLT2 inhibitors treatment was significantly superior to metformin treatment in terms of reducing body weight (P = 0.02, I2 = 36%), decreasing dehydroepiandrosterone sulfate concentrations [SMD = -0.42, 95% CI (-0.76, -0.07), I2 = 22%, P = 0.02], and reducing the incidence of nausea [RR = 0.35, 95% CI (0.21, 0.60), I2 = 71%, P = 0.0001]. CONCLUSIONS: SGLT2 inhibitors are a possible alternative therapy for treating overweight/obese women with PCOS who do not respond favorably to metformin treatment. However, further large randomized controlled trials and cost-effectiveness analyses are warranted to guide the implementation of SGLT2 inhibitors treatment in this population.

14.
Transl Androl Urol ; 12(8): 1336-1350, 2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37680229

RESUMO

Background: Androgen deprivation therapy (ADT) is an effective prostate cancer (PCa) treatment strategy that can curb the development or progression of the disease. This review aimed to examine and summarize available systematic reviews/meta-analyses (SRs/MAs) of exercise training on physical condition of PCa patients undergoing ADT. Methods: A comprehensive search of 8 databases was conducted for relevant literature published before April 25, 2022 with the language restrictions of Chinese and English. Two reviewers independently assessed the methodological quality, risk of bias, reporting quality, and evidence quality of the included SRs/MAs using a range of evaluation tools, including A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2, Risk of Bias in Systematic Reviews (ROBIS), the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and Grades of Recommendations, Assessment, Development and Evaluation (GRADE). Results: This review included 8 SRs/MAs which included a total of 94 studies. Ultimately, A total of 51 outcomes was included, regarding 11 different outcome categories. The AMSTAR-2 tool showed that 3 SRs/MAs had moderate methodological quality, 4 SRs/MAs had very low quality, and the remaining 1 had low quality. According to the ROBIS scale, 3 SRs/MAs had a high risk of bias. The PRISMA checklist showed that the primary reporting faults were protocol registration and funding source. The GRADE system was used to analyze the evidence quality of the 51 outcomes, and no high-quality evidence was found. However, moderate-quality evidence indicated that exercise training may improve body composition [by lowering body fat mass (BFM) and body fat rate (BFR)], muscular strength, and quality of life (QoL) in PCa patients undergoing ADT. Low-quality evidence demonstrated that exercise training could improve such symptoms as fatigue, depression, sexual function, and cardiometabolic changes. Conclusions: Available evidence suggests that exercise training may be used as an adjuvant treatment for PCa patients undergoing ADT to improve several aspects of general health. Studies with more rigorous designs and larger sample sizes are needed to support our findings with more robust evidence.

15.
World J Surg Oncol ; 21(1): 185, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37344861

RESUMO

BACKGROUND: We previously reported joint-sparing tumor resection for osteosarcoma with epiphyseal involvement in which transepiphyseal osteotomy went through the in situ ablated epiphysis. However, we do not know whether this is a safe approach when compared with joint-sacrificed tumor resection. Our objective was to compare oncologic and functional outcomes between patients who underwent joint preservation (JP) and joint replacement (JR) tumor resection. Furthermore, we identified the risk factors of local recurrence, metastasis and survival. METHODS: Eighty-nine patients with non-metastatic high-grade osteosarcoma around the knee were treated with limb-salvage surgery (JP in 47 and JR in 42). Age, gender, tumor location, pathologic fracture, plain radiographic pattern, limb diameter change, perivascular space alteration, surgical margin, local recurrence, metastasis, death, and the Musculoskeletal Tumor Society (MSTS)-93 scores were extracted from the records. Univariate analysis was performed to compare oncologic and functional outcomes. Binary logistic and cox regression models were used to identify predicted factors for local recurrence, metastasis, and survival. RESULTS: Local recurrence, metastasis and overall survival were similar in the JP and JR group (p = 0.3; p = 0.211; p = 0.143). Major complications and limb survival were also similar in the JR and JP group (p = 0.14; p = 0.181). The MSTS score of 27.06 ± 1.77 in the JP group was higher than that of 25.88 ± 1.79 in the JR group (p = 0.005). The marginal margin of soft tissue compared with a wide margin was the only independent predictor of local recurrence (p = 0.006). Limb diameter increase and perivascular fat plane disappearance during neoadjuvant chemotherapy were independent predictors for metastasis (p = 0.002; p = 0.000) and worse survival (p = 0.000; p = 0.001). CONCLUSIONS: Joint-sparing tumor resection with the ablative bone margin offers advantage of native joint preservation with favorable functional outcomes while not jeopardizing oncologic outcomes compared with joint-sacrificed tumor resection. Surgeon should strive to obtain adequate soft tissue surgical margin decreasing risk of local recurrence. Novel drug regimens might be reasonable options for patients with obvious limb diameter increase and perivascular fat disappearance during chemotherapy.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Margens de Excisão , Neoplasias Ósseas/patologia , Extremidade Inferior/patologia , Osteossarcoma/patologia , Salvamento de Membro , Estudos Retrospectivos , Resultado do Tratamento
16.
Pharm Biol ; 61(1): 271-280, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36655371

RESUMO

CONTEXT: Therapeutic effects of Qiangjing tablets (QJT) on sperm vitality and asthenozoospermia (AZS) have been confirmed. However, the mechanism of action remains unclear. OBJECTIVE: This study investigates the effects of QJT on AZS and the underlying mechanism of action. MATERIALS AND METHODS: Sixty Sprague-Dawley rats were randomly divided into six groups: Control, ORN (ornidazole; 200 mg/kg), ORN + QJT-low (0.17 g/mL), ORN + QJT-middle (0.33 g/mL), ORN + QJT-high (0.67 g/mL), and ORN + QJT + Radicicol (0.67 g/mL QJT and 20 mg/kg radicicol) groups. Pathological evaluation and analysis of mitophagy were conducted by H&E staining and transmission electron microscopy, respectively. Reactive oxygen species were detected by flow cytometry. Protein expression was determined by Western blotting. RESULTS: QJT significantly improved ORN-treated sperm motility and kinematic parameters, as well as the pathological symptoms of testicular and epididymal tissues. In particular, QJT mitigated impaired mitochondrial morphology, and increased the PHB, Beclin-1, LC3-II protein, and ROS levels (p < 0.05), and reduced the protein expression levels of LC3-I and p62 (p < 0.05). Mechanistically, QJT antagonized the downregulation of SCF and Parkin protein levels (p < 0.05). Furthermore, QJT significantly increased the protein expressions levels of LKB1, AMPKα, p-AMPKα, ULK1 and p-ULK1 (p < 0.05). The ameliorative effect of QJT on pathological manifestations, mitochondrial morphology, and the expressions of mitophagy and mitochondrial ubiquitination-related proteins was counteracted by radicicol. DISCUSSION AND CONCLUSIONS: QJT improved AZS via mitochondrial ubiquitination and mitophagy mediated by the LKB1/AMPK/ULK1 signaling pathway. Our study provides a theoretical basis for the treatment of AZS and male infertility.


Assuntos
Astenozoospermia , Medicamentos de Ervas Chinesas , Animais , Masculino , Ratos , Proteínas Quinases Ativadas por AMP , Astenozoospermia/tratamento farmacológico , Proteína Homóloga à Proteína-1 Relacionada à Autofagia , Medicamentos de Ervas Chinesas/uso terapêutico , Peptídeos e Proteínas de Sinalização Intracelular/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/uso terapêutico , Mitofagia , Ratos Sprague-Dawley , Sêmen , Motilidade dos Espermatozoides , Comprimidos/uso terapêutico , Ubiquitinação
17.
Opt Express ; 30(13): 23953-23966, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-36225066

RESUMO

High speed physical secure key distribution in a classical optical fiber channel is unprecedentedly desired for modern secure communication, but it still remains a worldwide technical challenge. In this paper, we propose and experimentally demonstrate a novel high-speed physical secure key distribution scheme based on chaotic optical signal processing and private hardware modules, which employs chaotic self-carrier phase modulation for chaotic bandwidth expansion and time-delayed shift keying of commonly driven synchronized optical chaos for physical layer security. In this scheme, the entropy source rate of synchronized chaos output from two remote response lasers is greatly expanded by chaotic self-carrier delayed nonlinear phase disturbance, which facilitates high speed key extraction from the entropy source with guaranteed randomness. Moreover, a synchronization recovery time of sub-nanosecond is achieved by dynamic keying of the chaotic delay time after chaos synchronization to accelerate the key distribution rate. Based on the proposed scheme, a high physical key distribution rate of 2.1 Gb/s over 40 km is successfully demonstrated in the experiment. The proposed solution provides a promising strategy for future high-speed key distribution based on chaotic optical signal processing and classical fiber channel.

18.
J Plast Reconstr Aesthet Surg ; 75(9): 3149-3154, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35915017

RESUMO

PURPOSE: The purpose of this study was to examine whether the results of a reconstruction using frozen autograft in combination with vascularized fibula are comparable to other reconstructive methods in limb-salvage surgery for tibial sarcoma with regard to the functional outcome and complications. METHODS: Between 2008 and 2012, nine patients with bone sarcoma of the tibia underwent excision of the affected segment that was then frozen and reimplanted with an ipsilateral vascularized fibular graft within it. Patients were examined clinically and radiographically. RESULTS: The mean follow-up was 48.8 months. The mean time to full weight-bearing was 6.2 months and to complete radiological union 6.8 months at the conjunction. One patient required a mid-thigh amputation due to local recurrence in soft tissue. No local recurrence arising from the frozen autograft was detected. Complications included wound dehiscence in 1, clawed toes in 1, temporary peroneal nerve palsy in 1, and stress fracture in 1. The average musculoskeletal tumor society functional score was 94.5%. CONCLUSIONS: Combination of a frozen tumor-bearing autograft and ipsilateral pedicled fibula is an effective reconstruction for massive bone defect arising from resection of bone sarcoma in tibia. This approach has the advantage of combining the biological properties offered by the vascularized bone graft with the mechanical endurance of the frozen autograft. The method is best indicated for intercalary defects of the tibia for selected patients. LEVEL OF EVIDENCE: Level IV, therapeutic study.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Procedimentos de Cirurgia Plástica , Sarcoma , Autoenxertos/patologia , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Transplante Ósseo/métodos , Fíbula/transplante , Humanos , Salvamento de Membro/métodos , Osteossarcoma/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Sarcoma/patologia , Sarcoma/cirurgia , Tíbia/cirurgia , Resultado do Tratamento
19.
Arch Microbiol ; 204(8): 475, 2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35829834

RESUMO

A Gram-negative, aerobic, chemoheterotrophic, rod-shaped, and motile bacterium, designated as LST-1T, was isolated from wild Stevia rebaudiana Bertoni and subjected to a polyphasic taxonomic analysis. The LST-1 strain grew optimally at 37 °C and pH 6.0-7.0 in the presence of 0.5% (w/v) NaCl. Phylogenetic analysis based on the 16S rDNA sequence indicated that LST-1 is closely related to Lelliottia jeotgali PFL01T (99.85%), Lelliottia nimipressuralis LMG10245T (98.82%), and Lelliottia amnigena LMG2784T (98.54%). Multi-locus sequence typing of concatenated partial atpD, infB, gyrB, and rpoB genes was performed to improve the resolution, and clear distinctions between the closest related type strains were observed. The results of average nucleotide identify analyses and DNA-DNA hybridization with four species (16S rDNA similarity > 98.65%) were less than 90 and 40%, respectively, verifying the distinct characteristics from other species of Lelliottia. The cellular fatty acid profile of the strain consisted of C16:0, Summed Feature3, and Summed Feature8 (possibly 16:1 w6c/16:1 w7c and 18:1 w6c) as major components. The major polar lipids included phosphatidylethanolamine, phosphatidylglycerol, an aminophospholipid, three non-characteristic phospholipids, and a non-characteristic lipid. The genome of LST-1T was 4,611,055 bp in size, with a G + C content of 55.02%. The unique combination of several phenotypic, chemotaxonomic, and genomic characteristics proved that strain LST-1T belongs to a novel species, for which the name Lelliottia steviae sp. nov. is proposed. The type strain is LST-1T (= CGMCC 1.19175T = JCM 34938T).Repositories: The genbank accession numbers for the 16S rRNA gene and genome sequences of strain LST-1T are MZ497264 and CP063663, respectively.


Assuntos
Stevia , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , DNA Ribossômico , Ácidos Graxos/análise , Tipagem de Sequências Multilocus , Hibridização de Ácido Nucleico , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Stevia/genética
20.
Pain Res Manag ; 2022: 9448620, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573644

RESUMO

Evidence shows that chronic prostatitis/chronic pelvic pain syndrome hugely impacts the body and mind. The central mechanisms in patients with CP/CPPS resulted in increased attention as neuroimaging techniques developed. This review investigated the study design and major neuroimaging findings in CP/CPPS patients to provide comprehensive evidence. Seven databases were searched and screened: PubMed, EMBASE/SCOPUS, Cochrane Library Database, China National Knowledge Infrastructure, VIP, Wanfang, and China Biology Medicine disc. Nine studies were eventually included in the analysis. The results demonstrate that the insula, anterior cingulate gyrus, postcentral gyrus, and precuneus are significantly associated with CP/CPPS patients' pain feelings and cause dysregulation of painful emotions, lowering patients' tolerance to stimulus.


Assuntos
Dor Crônica , Prostatite , Doença Crônica , Dor Crônica/complicações , Dor Crônica/diagnóstico por imagem , Humanos , Masculino , Neuroimagem , Dor Pélvica/diagnóstico por imagem , Prostatite/complicações , Prostatite/diagnóstico por imagem , Projetos de Pesquisa
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