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1.
J Orthop Surg Res ; 19(1): 123, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38317253

RESUMO

BACKGROUND: We aim to compare and assess the surgical parameters and follow-up information of one-hole split endoscopic discectomy (OSE) and microendoscopic discectomy (MED) in the treatment of LDH. METHODS: This study included 154 patients with degenerative lumbar disk disease. Sixty-eight patients underwent OSE and 86 patients MED. The VAS score for lower back and lower limb radiation pain, ODI score, modified MacNab score, estimated blood loss (EBL), length of the incision, amount of C-reactive protein, and recurrence and complication rates were examined as indicators for clinical outcomes and adverse events. RESULTS: After surgery, the VAS and ODI scores in the two groups significantly decreased. On the third day after surgery, the VAS and ODI scores of the OSE group were significantly better than those of the MED group. The VAS and ODI scores preoperatively and at 1 month, 3 months, 6 months, and 12 months following the procedure did not substantially vary between the two groups. There was less EBL and a shorter incision with OSE than with MED. There was no significant difference in the rate of complications between the two groups. CONCLUSION: Compared with MED, OSE is a new alternative option for LDH that can achieve similar and satisfactory clinical outcomes. Furthermore, OSE has many advantages, including less EBL and a smaller incision. Further clinical studies are needed to confirm the effectiveness of OSE.


Assuntos
Discotomia Percutânea , Deslocamento do Disco Intervertebral , Ferida Cirúrgica , Humanos , Deslocamento do Disco Intervertebral/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Vértebras Lombares/cirurgia , Discotomia/efeitos adversos , Discotomia/métodos , Endoscopia/métodos , Dor/etiologia , Ferida Cirúrgica/etiologia , Discotomia Percutânea/métodos
2.
World J Clin Cases ; 12(3): 587-595, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38322461

RESUMO

BACKGROUND: Paramyotonia congenita (PMC) stands as a rare sodium channelopaty of skeletal muscle, initially identified by Eulenburg. The identification of PMC often relies on electromyography (EMG), a diagnostic technique. The child's needle EMG unveiled trains of myotonic discharges with notably giant amplitudes, alongside irregular wave trains of myotonic discharges. This distinctive observation had not surfaced in earlier studies. CASE SUMMARY: We report the case of a 3-year-old female child with PMC, who exhibited laryngeal stridor, muffled speech, myotonia from birth. Cold, exposure to cool water, crying, and physical activity exacerbated the myotonia, which was relieved in warmth, yet never normalized. Percussion myotonia was observable in bilateral biceps. Myotonia symptoms remained unchanged after potassium-rich food consumption like bananas. Hyperkalemic periodic paralysis was excluded. Cranial magnetic resonance imaging yielded normal results. Blood potassium remained within normal range, while creatine kinase showed slight elevation. Exome-wide genetic testing pinpointed a heterozygous mutation on chromosome SCN4A: c.3917G>A (p.G1306E). After a six-month mexiletine regimen, symptoms alleviated. CONCLUSION: In this case revealed the two types of myotonic discharges, and had not been documented in other studies. We underscore two distinctive features: Giant-amplitude potentials and irregular waves.

3.
Cell Biol Int ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321831

RESUMO

Osteoporosis is a chronic skeletal disease and the major source of risk for fractures in aged people. It is urgent to investigate the mechanism regulating osteoporosis for developing potential treatment and prevention strategies. Osteogenic differentiation of preosteoblast enhances bone formation, which might be a promising strategy for treatment and prevention of osteoporosis. Protein disulfide isomerase family A, member 3 (PDIA3) could induce bone formation, yet the role of PDIA3 in osteogenic differentiation of preosteoblast remains unknown. In this study, m6 A RNA methylation was detected by methylated RNA immunoprecipitation (MeRIP), while mRNA stability was identified by RNA decay assay. Besides, protein-protein interaction and protein phosphorylation were determined using co-immunoprecipitation (Co-IP). Herein, results revealed that PDIA3 promoted osteogenic differentiation of preosteoblast MC3T3-E1. Besides, PDIA3 mRNA methylation was suppressed by FTO alpha-ketoglutarate dependent dioxygenase (FTO) as RNA methylation reduced PDIA3 mRNA stability during osteogenic differentiation of MC3T3-E1 cells. Moreover, ubiquitin specific peptidase 20 (USP20) improved FTO level through inhibiting FTO degradation while PDIA3 increased FTO level by enhancing USP20 phosphorylation during osteogenic differentiation of MC3T3-E1 cells, suggesting a positive feedback regulatory loop between PDIA3 and FTO. In summary, these findings indicated the mechanism of PDIA3 regulating osteogenic differentiation of preosteoblast and provided potential therapeutic targets for osteoporosis.

4.
ESC Heart Fail ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38327133

RESUMO

AIMS: This study investigated the S2 I2 N0-3 score, a simple tool comprising stroke history, insulin-treated diabetes, and N-terminal pro-brain natriuretic peptide, for forecasting mortality and morbidity in heart failure (HF) with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Analysing 890 GUIDE-IT HFrEF trial participants, we stratified them by baseline S2 I2 N0-3 risk score into three risk groups. We examined the score's association with five adverse outcomes over short (90 days) and extended periods (median follow-up of 15 months) using Cox and competing risk models. Our analysis revealed significant positive associations between the S2 I2 N0-3 strata and adverse outcomes. When analysed as a continuous variable, each point increment of the S2 I2 N0-3 score was associated with a higher risk of short- and long-term cardiovascular death [short term: hazard ratio (HR) 1.43, 95% confidence interval (CI) 1.03-1.98; long term: HR 1.18, 95% CI 1.02-1.38], all-cause death (HR 1.52, 95% CI 1.12-2.07; HR 1.18, 95% CI 1.03-1.36), HF hospitalization (HR 1.39, 95% CI 1.20-1.62; HR 1.18, 95% CI 1.06-1.31), any hospitalization (HR 1.19, 95% CI 1.06-1.34; HR 1.09, 95% CI 1.00-1.19), and the composite outcome of cardiovascular death and HF hospitalization (HR 1.39, 95% CI 1.21-1.60; HR 1.17, 95% CI 1.06-1.30). The S2 I2 N0-3 demonstrated reliable prognostic value, with C-indices ranging from 0.619 to 0.753 across outcomes and time points. When compared with the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score using Z-statistics, net reclassification index, and integrated discrimination improvement, the S2 I2 N0-3 showed comparable predictive power for all outcomes during both short- and long-term follow-ups. CONCLUSIONS: The S2 I2 N0-3 risk score had modest predictive values for both short- and long-term clinical outcomes in HFrEF patients, offering equivalent performance to the established MAGGIC score.

5.
Mol Oral Microbiol ; 2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38311876

RESUMO

Orthotopic allograft transplantation (OAT) is a significant approach to addressing organ failure. However, persistent immune responses to the allograft affect chronic rejection, which induces OAT vasculopathy (OATV) and organ failure. Porphyromonas gingivalis can infiltrate remote organs via the bloodstream, thereby intensifying the severity of cardiovascular, respiratory, and neurodegenerative diseases and cancer. GroEL, a virulence factor of P. gingivalis promotes pro-inflammatory cytokine production in host cells, which assumes to play a pivotal role in the pathogenesis of cardiovascular diseases. Although the aggravation of OATV is attributable to numerous factors, the role of GroEL remains ambiguous. Therefore, this study aimed to investigate the impact of GroEL on OATV. Aortic grafts extracted from PVG/Seac rats were transplanted into ACI/NKyo rats and in vitro human endothelial progenitor cell (EPC) and coronary artery endothelial cell (HCAEC) models. The experimental findings revealed that GroEL exacerbates OATV in ACI/NKyo rats by affecting EPC and smooth muscle progenitor cell (SMPC) function and enabling the anomalous accumulation of collagen. In vitro, GroEL spurs endothelial-mesenchymal transition in EPCs, reduces HCAEC tube formation and barrier function by downregulating junction proteins, accelerates HCAEC aging by lowering mitochondrial membrane potential and respiratory function, and impedes HCAEC migration by modulating cytoskeleton-associated molecules. This study suggests that P. gingivalis GroEL could potentially augment OATV by impacting vascular progenitor and endothelial cell functions.

6.
J Formos Med Assoc ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38341328

RESUMO

Studies have associated the development of pulmonary leukemia with the activation of the complement system. However, the roles and mechanisms of complement system-related genes (CSRGs) in acute myeloid leukemia (AML) have not been investigated extensively. This study used The Cancer Genome Atlas (TCGA)-AML and GSE37642 datasets. Differentially expressed CSRGs (CSRDEGs) were identified by overlapping genes differentially expressed between the high and low CSRG score groups and key module genes identified in a weighted gene co-expression network analysis. Univariate and multivariate Cox analyses identified CSRG-related biomarkers, which were used to build a prognostic model. After gene set enrichment analysis (GSEA), immune-related and drug-sensitivity analyses were performed in the high- and low-risk groups. Four prognosis-related biomarkers were identified and used to develop a prognostic model: MEOX2, IGFBP5, CH25H, and RAB3B. The model's performance was verified in a test cohort (a subset of samples from the TCGA-AML dataset) and a validation cohort (GSE37642). The GSEA revealed that the high-risk group was mainly enriched for Golgi organization and cytokine-cytokine receptor interactions, and the low-risk group was mainly enriched in the hedgehog signaling pathway and spliceosome. Lastly, two immune cells were found to show differential infiltration between risk groups, which correlated with the risk scores. M1 macrophage infiltration was significantly positively correlated with RAB3B expression. Sensitivity to 36 drugs differed significantly between risk groups. This study screened four CSRG-related biomarkers (MEOX2, IGFBP5, CH25H, and RAB3B) to provide a basis for predicting AML prognosis.

7.
J Cell Physiol ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38345407

RESUMO

Mechanical environment worsening is an important predisposing factor that accelerates intervertebral disc degeneration (IDD), but its specific regulatory mechanisms remain unclear. In this study, we reveal the molecular mechanisms of WTAP/YTHDF2-mediated m6A modification in abnormal stress-induced intervertebral disc (IVD) matrix degradation. WTAP expression in human nucleus pulposus cells was elevated under tension. Similarly, high WTAP expression was detected in severe degenerated human and rat nucleus pulposus tissues. Functionally, WTAP was found to increase the TIMP3 transcript methylation level under tension, resulting in YTHDF2 recognition, binding, and induction of its degradation. Reduction in TIMP3 caused increases in active matrix metalloproteinases, ultimately inducing extracellular matrix degradation in nucleus pulposus cells. Macroscopically, this promotes IDD. Additionally, in vitro and in vivo inhibition of WTAP expression or TIMP3 overexpression significantly increased stress resistance in the nucleus pulposus, thereby alleviating IDD. Our results show that abnormal stress disrupts IVD matrix stability through WTAP/YTHDF2-dependent TIMP3 m6A modification.

8.
J Oleo Sci ; 73(2): 201-213, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38311410

RESUMO

Effects of dry and wet grind on peanut oil and protein yield, oil bodies (OBs) stability, fatty acid composition, protein composition and functional characteristics were systematically analyzed. Results showed that peanut oil and protein yields reached highest at dry grind 90 s (92.56% and 83.05%, respectively), while peanut oil and protein yields were 94.58% and 85.36%, respectively, at wet grind 120 s. Peanut oil and protein yields by wet grind was 2.18% and 2.78% higher than that of dry grind, respectively. Surface protein concentration (Г) and absolute value of zeta potential of OBs extracted by wet grind (WOBs) were 11.53 mg/m 2 and 18.51 mV, respectively, which were higher than OBs extracted by dry grind (DOBs), indicating stability of WOBs was higher than DOBs. Relative contents of oleic acid and linoleic acid in peanut oil, essential and hydrophobic amino acids in protein extracted by wet grind were higher than dry grind. There was little difference in protein composition between wet and dry grind, but thermal denaturation degree of protein obtained by wet grind was lower than dry grind. Solubility, oil retention, emulsion stability, foaming and foam stability of protein obtained by wet grind were better than dry grind. Results from this study provided theoretical basis for grind pretreatment selection of aqueous enzymatic method.


Assuntos
Arachis , Gotículas Lipídicas , Óleo de Amendoim/química , Arachis/química , Gotículas Lipídicas/química , Ácidos Graxos/análise , Solubilidade
9.
J Transl Med ; 22(1): 125, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38303030

RESUMO

BACKGROUND: Previous studies have shown that changes in the microbial community of the female urogenital tract are associated with Human papillomavirus (HPV) infection. However, research on this association was mostly focused on a single site, and there are currently few joint studies on HPV infection and multiple sites in the female urogenital tract. METHODS: We selected 102 healthy women from Yunnan Province as the research object, collected cervical exfoliation fluid, vaginal, urethral, and rectal swabs for microbial community analysis, and measured bacterial load, and related cytokine content. The link between HPV, microbiota, and inflammation was comprehensively evaluated using bioinformatics methods. FINDINGS: The impact of HPV infection on the microbial composition of different parts varies. We have identified several signature bacterial genera that respond to HPV infection in several detection sites, such as Corynebacterium, Lactobacillus, Campylobacter, and Cutibacterium have been detected in multiple sites, reflecting their potential significance in cross body sites HPV infection responses. There was a solid microbial interaction network between the cervix, vagina, and urethra. The interrelationships between inflammatory factors and different bacterial genera might also affect the immune system's response to HPV infection. INTERPRETATION: It might be an effective strategy to prevent and treat HPV infection by simultaneously understanding the correlation between the microbial changes in multiple parts of the female urogenital tract and rectum and HPV infection, and controlling the microbial network related to HPV infection in different parts.


Assuntos
Infecções por Papillomavirus , Reto , Feminino , Humanos , China , Vagina/microbiologia , Bactérias , RNA Ribossômico 16S , Papillomaviridae
10.
Stem Cell Res ; 76: 103335, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38364504

RESUMO

Neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV, #615075), a rare autosomal dominant genetic disorder caused by heterozygous mutation in the CTNNB1 gene, is characterized by global developmental delay, impaired intellectual development, axial hypotonia, and dysmorphic craniofacial features with microcephaly. Here, we established an iPSC line (SDQLCHi055-A) from a patient with NEDSDV carrying a heterozygote mutation (c.854 T > A, p.L285*) in the CTNNB1 gene. The iPSC line has typical iPSCs characteristics, including pluripotency and trilineage differentiation hallmarks.

11.
Front Psychol ; 15: 1324415, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38356766

RESUMO

Background and objectives: This study's primary objective is to investigate the impact of art-making on the mental well-being of college students, who often experience heightened stress during their initial university years. Methods: Employing a comprehensive methodology, combining interviews and the Perceived Stress Scale (PSS), the research aimed to assess whether a four-week art-making intervention can effectively alleviate stress levels among college students. In the experimental group, participants engaged in a variety of art-making activities, including freehand drawing, clay modeling, and crafting. Results: The results revealed that, in the pre-test, there were no significant differences between the experimental and control groups for each assessed indicator. However, in the post-test, significant differences emerged across all indicators. Further analysis demonstrated a significant reduction in stress perception among the experimental group participants between the pre-test and post-test phases. Conclusion: In conclusion, this study provides compelling evidence that art-making has the potential to foster positive personal development and significantly reduce stress levels among college students.

12.
EClinicalMedicine ; 69: 102482, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38374967

RESUMO

Background: Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease and is associated with high mortality rates. The influence of routine clinical parameters on DKD onset in patients with type 2 diabetes mellitus (T2DM) remains uncertain. Methods: In this systematic review and meta-analysis, we searched multiple databases, including PubMed, Embase, Scopus, Web of Science, and Cochrane Library, for studies published from each database inception until January 11, 2024. We included cohort studies examining the association between DKD onset and various clinical parameters, including body mass index (BMI), hemoglobin A1c (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and serum uric acid (UA). Random-effect dose-response meta-analyses utilizing one-stage and/or cubic spline models, were used to estimate correlation strength. This study is registered in PROSPERO (CRD42022326148). Findings: This analysis of 46 studies involving 317,502 patients found that in patients with T2DM, the risk of DKD onset increased by 3% per 1 kg/m2 increase in BMI (relative risk (RR) = 1.03, confidence interval (CI) [1.01-1.04], I2 = 70.07%; GRADE, moderate); a 12% increased risk of DKD onset for every 1% increase in HbA1c (RR = 1.12, CI [1.07-1.17], I2 = 94.94%; GRADE, moderate); a 6% increased risk of DKD onset for every 5 mmHg increase in SBP (RR = 1.06. CI [1.03-1.09], I2 = 85.41%; GRADE, moderate); a 2% increased risk of DKD onset per 10 mg/dL increase in TG (RR = 1.02, CI [1.01-1.03], I2 = 78.45%; GRADE, low); an 6% decreased risk of DKD onset per 10 mg/dL increase in HDL (RR = 0.94, CI [0.92-0.96], I2 = 0.33%; GRADE, high), and a 11% increased risk for each 1 mg/dL increase in UA (RR = 1.11, CI [1.05-1.17], I2 = 79.46%; GRADE, moderate). Subgroup analysis revealed a likely higher risk association of clinical parameters (BMI, HbA1c, LDL, and UA) in patients with T2DM for less than 10 years. Interpretation: BMI, HbA1c, SBP, TG, HDL and UA are potential predictors of DKD onset in patients with T2DM. Given high heterogeneity between included studies, our findings should be interpreted with caution, but they suggest monitoring of these clinical parameters to identify individuals who may be at risk of developing DKD. Funding: Shenzhen Science and Innovation Fund, the Hong Kong Research Grants Council, and the HKU Seed Funds, and Scientific and technological innovation project of China Academy of Chinese Medical Sciences.

13.
J Chem Phys ; 160(7)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38380751

RESUMO

In this study, the total ion yield near-edge x-ray absorption fine structure spectra of four similar peptoid molecules, which differ in the numbers and positions of methyl groups, were investigated experimentally and theoretically. At each excitation energy, the intensity and branching ratio of each ionic product were measured. At a few resonant excitation energies, a specific dissociation of the C-CO bond at the nitrogen and oxygen K-edges and of the N-CO bond at the carbon K-edge was dominant, which correlated well with the predicted destination antibonding orbitals of the core electron excitation. These specific dissociation mechanisms of small peptoid molecules could provide insights into similar phenomena that occur in peptide molecules.

14.
Front Immunol ; 15: 1343450, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38361936

RESUMO

Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers. In recent years, treatment with immune checkpoint inhibitors (ICIs) has gradually improved the survival rate of patients with NSCLC, especially those in the advanced stages. ICIs can block the tolerance pathways that are overexpressed by tumor cells and maintain the protective activity of immune system components against cancer cells. Emerging clinical evidence suggests that gut microbiota may modulate responses to ICIs treatment, possibly holding a key role in tumor immune surveillance and the efficacy of ICIs. Studies have also shown that diet can influence the abundance of gut microbiota in humans, therefore, dietary interventions and the adjustment of the gut microbiota is a novel and promising treatment strategy for adjunctive cancer therapy. This review comprehensively summarizes the effects of gut microbiota, antibiotics (ATBs), and dietary intervention on the efficacy of immunotherapy in NSCLC, with the aim of informing the development of novel strategies in NSCLC immunotherapy.


Assuntos
Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Microbioma Gastrointestinal , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1 , Imunoterapia
15.
ISME J ; 18(1)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38365252

RESUMO

A key aspect of "One Health" is to comprehend how antibiotic resistomes evolve naturally. In this issue, Nguyen and colleagues pioneered an in situ investigation on the impact of protist predations on the soil microbial community and its antibiotic resistance genes (ARGs). They found that bacterivorous protists consistently increased the abundance of ARGs, such as tetracycline resistant genes. Indeed, antibiotic production is a common strategy for bacteria to evade protist predation. The rise of ARGs can be explained by the balance between antibiotic producers and resisters shaped by predatory selection. This work suggests that ARG enrichment due to biotic interactions may be less worrisome than previously thought. Unless, these ARGs are carried by or disseminated among pathogens. Therefore, it is essential to monitor the occurrence, dissemination and pathogenic hosts of ARGs, enhancing our capacity to combat antibiotic resistance.


Assuntos
Genes Bacterianos , Solo , Animais , Comportamento Predatório , Microbiologia do Solo , Antibacterianos/farmacologia
16.
Hypertension ; 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38390718

RESUMO

BACKGROUND: Wave separation analysis enables individualized evaluation of the aortic pulse wave components. Previous studies focused on the pressure height with overall positive but differing results. In the present analysis, we assessed the associations of the pressure of forward and backward (Pfor and Pref) pulse waves with prospective cardiovascular end points, with extended analysis for time to pressure peak (Tfor and Tref). METHODS: Participants in 3 IDCARS (International Database of Central Arterial Properties for Risk Stratification) cohorts (Argentina, Belgium, and Finland) aged ≥20 years with valid pulse wave analysis and follow-up data were included. Pulse wave analysis was done using the SphygmoCor device, and pulse wave separation was done using the triangular method. The primary end points consisted of cardiovascular mortality and nonfatal cardiovascular and cerebrovascular events. Multivariable-adjusted Cox regression was used to calculate hazard ratios. RESULTS: A total of 2206 participants (mean age, 57.0 years; 55.0% women) were analyzed. Mean±SDs for Pfor, Pref, Tfor, and Tfor/Tref were 31.0±9.1 mm Hg, 20.8±8.4 mm Hg, 130.8±35.5 ms, and 0.51±0.11 ms, respectively. Over a median follow-up of 4.4 years, 146 (6.6%) participants experienced a primary end point. Every 1 SD increment in Pfor, Tfor, and Tfor/Tref was associated with 27% (95% CI, 1.07-1.49), 25% (95% CI, 1.07-1.45), and 32% (95% CI, 1.12-1.56) higher risk, respectively. Adding Tfor and Tfor/Tref to existing risk models improved model prediction (∆Uno's C, 0.020; P<0.01). CONCLUSIONS: Pulse wave components were predictive of composite cardiovascular end points, with Tfor/Tref showing significant improvement in risk prediction. Pending further confirmation, the ratio of time to forward and backward pressure peak may be useful to evaluate increased afterload and signify increased cardiovascular risk.

17.
BMC Genomics ; 25(1): 198, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378450

RESUMO

BACKGROUND: Cervical cancer (CC) causes more than 311,000 deaths annually worldwide. The integration of human papillomavirus (HPV) is a crucial genetic event that contributes to cervical carcinogenesis. Despite HPV DNA integration is known to disrupt the genomic architecture of both the host and viral genomes in CC, the complexity of this process remains largely unexplored. RESULTS: In this study, we conducted whole-genome sequencing (WGS) at 55-65X coverage utilizing the PacBio long-read sequencing platform in SiHa and HeLa cells, followed by comprehensive analyses of the sequence data to elucidate the complexity of HPV integration. Firstly, our results demonstrated that PacBio long-read sequencing effectively identifies HPV integration breakpoints with comparable accuracy to targeted-capture Next-generation sequencing (NGS) methods. Secondly, we constructed detailed models of complex integrated genome structures that included both the HPV genome and nearby regions of the human genome by utilizing PacBio long-read WGS. Thirdly, our sequencing results revealed the occurrence of a wide variety of genome-wide structural variations (SVs) in SiHa and HeLa cells. Additionally, our analysis further revealed a potential correlation between changes in gene expression levels and SVs on chromosome 13 in the genome of SiHa cells. CONCLUSIONS: Using PacBio long-read sequencing, we have successfully constructed complex models illustrating HPV integrated genome structures in SiHa and HeLa cells. This accomplishment serves as a compelling demonstration of the valuable capabilities of long-read sequencing in detecting and characterizing HPV genomic integration structures within human cells. Furthermore, these findings offer critical insights into the complex process of HPV16 and HPV18 integration and their potential contribution to the development of cervical cancer.


Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/genética , Células HeLa , Infecções por Papillomavirus/genética , DNA , Genômica , Integração Viral/genética
18.
J Pharmacol Exp Ther ; 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409113

RESUMO

While agonists of mu (MOR) and kappa (KOR) opioid receptors have analgesic effects, they produce euphoria and dysphoria, respectively. Other side effects include respiratory depression and addiction for MOR agonists and sedation for KOR agonists. We reported that 17-cyclopropylmethyl-3,14ß-dihydroxy-4,5α-epoxy-6ß-{[4'-(2'-cyanopyridyl)]carboxamido}cmorphinan (NCP) displayed potent KOR full agonist and MOR partial agonist activities (58%) with 6.5x KOR-over-MOR selectivity in vitro Herein, we characterized pharmacological effects of NCP in rodents. In mice, NCP exerted analgesic effects against inflammatory pain in both the formalin test and the acetic acid writhing test, with A50 values of 47.6 and 14.4 microg/kg (s.c.), respectively. The analgesic effects in the acetic acid writhing test were mediated by the KOR. NCP at doses much higher than those effective in reducing inflammatory pain did not produce antinociception in the hot plate and tail flick tests, inhibit compound 48/80-induced scratching, cause conditioned place aversion (CPA) or preference, impair rotarod performance, inhibit locomotor activity, cause respiratory depression, or precipitate morphine withdrawal. However, NCP (10~100 microg/kg) inhibited gastrointestinal transit with a maximum of ~40% inhibition. In MOR knockout mice, NCP caused CPA, demonstrating that its lack of CPA is due to combined actions on the MOR and KOR. Following s.c. injection, NCP penetrated into the mouse brain. In rats trained to self-administer heroin, NCP (1~320 microg/kg/infusion) did not function as a reinforcer. Thus, NCP produces potent analgesic effects via KOR without side effects except constipation. Therefore, dual full KOR/partial MOR agonists with moderate KOR-over-MOR selectivity may be promising as non-addictive analgesics for inflammatory pain. Significance Statement Developing non-addictive analgesics is crucial for reducing opioid overdose deaths, minimizing drug misuse, and promoting safer pain management practices. Herein, pharmacology of a potential non-addictive analgesic, NCP, is reported. NCP has full KOR agonist / partial MOR agonist activities with a 6.5 x selectivity for KOR over MOR. Unlike MOR agonists, analgesic doses of NCP do not lead to self-administration or respiratory depression. Furthermore, NCP does not produce aversion, hypolocomotion, or motor incoordination, side effects typically associated with KOR activation.

19.
Org Lett ; 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38407049

RESUMO

A novel method for electrochemical lactonization via C(sp3)-H functionalization was developed. This metal- and oxidant-free strategy enabled the efficient synthesis of various lactones. Gram-scale reaction and derivatization of the lactone product demonstrated the synthetic utility of this methodology. Mechanistic studies using control experiments and CV curves elucidated the proposed intramolecular HAT and the oxidative cyclization pathway. An unusual Shono-type oxidation was realized through this electrochemical approach, proceeding without a traditional nucleophilic addition process.

20.
Sci Rep ; 14(1): 4049, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374379

RESUMO

Master-slave blockchain is a novel information processing technology that is domain-oriented and uses efficient cryptography principles for trustworthy communication and storage of big data. Existing indexing methods primarily target the creation of a single-structured blockchain, resulting in extensive time and memory requirements. As the scale of domain data continues to grow exponentially, master-slave blockchain systems face increasingly severe challenges with regards to low query efficiency and extended traceback times. To address these issues, this paper propose a multi-level index construction method for the master-slave blockchain (MLI). Firstly, MLI introduces a weight matrix and partitions the entire master-slave blockchain based on the master chain structure, the weight of each partition is assigned. Secondly, for the master blockchain in each partition, a master chain index construction method based on jump consistent hash (JHMI) is proposed, which takes the key value of the nodes and the number of index slots as input and outputs the master chain index. Finally, a bloom filter is introduced to improve the column-based selection function and build a secondary composite index on the subordinate blockchain corresponding to each master block. Experimental results on three constraint conditions and two types of datasets demonstrate that the proposed method reduce the index construction time by an average of 9.28%, improve the query efficiency by 12.07%, and reduce the memory overhead by 24.4%.

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