Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 184
Filtrar
1.
Leukemia ; 38(5): 1115-1130, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38555405

RESUMO

Infant and adult MLL1/KMT2A-rearranged (MLLr) leukemia represents a disease with a dismal prognosis. Here, we present a functional and proteomic characterization of in utero-initiated and adult-onset MLLr leukemia. We reveal that fetal MLL::ENL-expressing lymphomyeloid multipotent progenitors (LMPPs) are intrinsically programmed towards a lymphoid fate but give rise to myeloid leukemia in vivo, highlighting a complex interplay of intra- and extracellular factors in determining disease subtype. We characterize early proteomic events of MLL::ENL-mediated transformation in fetal and adult blood progenitors and reveal that whereas adult pre-leukemic cells are mainly characterized by retained myeloid features and downregulation of ribosomal and metabolic proteins, expression of MLL::ENL in fetal LMPPs leads to enrichment of translation-associated and histone deacetylases signaling proteins, and decreased expression of inflammation and myeloid differentiation proteins. Integrating the proteome of pre-leukemic cells with their secretome and the proteomic composition of the extracellular environment of normal progenitors highlights differential regulation of Igf2 bioavailability, as well as of VLA-4 dimer and its ligandome, upon initiation of fetal- and adult-origin leukemia, with implications for human MLLr leukemia cells' ability to communicate with their environment through granule proteins. Our study has uncovered opportunities for targeting ontogeny-specific proteomic vulnerabilities in in utero-initiated and adult-onset MLLr leukemia.


Assuntos
Proteína de Leucina Linfoide-Mieloide , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/metabolismo , Humanos , Camundongos , Animais , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Rearranjo Gênico , Proteômica/métodos , Feto/metabolismo , Adulto , Feminino , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Leucemia/genética , Leucemia/patologia , Leucemia/metabolismo
2.
Int J Biol Macromol ; 263(Pt 2): 130372, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38395275

RESUMO

The present study reports the synthesis of micellar conjugates, wherein curcumin (Cur), a bioactive compound with poor bioavailability, was covalently bonded to a bacterial exopolysaccharide (EPS). These conjugates were synthesized by utilizing succinic acid that linked Cur to the pyranosyl moiety of the EPS. The Cur-EPS conjugates appeared as spherical micelles in aqueous solution and were found to have an average hydrodynamic diameter of 254 ± 2.7 nm. The micellar conjugates showed superior stability than Cur as evident from their negative surface charge (-27 ± 1.8 mV) and low polydispersity index (PDI) (0.33 ± 0.04). The in vitro studies on release kinetics helped elucidate the pH-responsive characteristics of the Cur-EPS conjugate, as 87.50 ± 1.45 % of Cur was released at an acidic pH of 5.6, in contrast to 30.15 ± 2.61 % at systemic pH of 7.4 at 150 h. The conjugates were hemocompatible and exhibited cytotoxic effect against the osteosarcoma cell line (MG-63) after 48 h treatment. They also demonstrated superior antibacterial, antibiofilm, and antioxidant activities in comparison to free Cur. Therefore, the Cur-EPS conjugates have potential pharmaceutical applications as therapeutic biomaterial that can be applied as a drug delivery system.


Assuntos
Antineoplásicos , Neoplasias Ósseas , Curcumina , Humanos , Curcumina/química , Micelas , Antineoplásicos/química , Sistemas de Liberação de Medicamentos , Neoplasias Ósseas/tratamento farmacológico , Concentração de Íons de Hidrogênio , Portadores de Fármacos/química
3.
Chemosphere ; 352: 141359, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38309604

RESUMO

Dibutyl phthalate (DBP) is a widely used plasticizer to make plastic flexible and long-lasting. It is easily accessible in a broad spectrum of environments as a result of the rising level of plastic pollution. This compound is considered a top-priority toxicant and persistent organic pollutant by international environmental agencies for its endocrine disruptive and carcinogenic propensities. To mitigate the DBP in the soil, one DBP-degrading bacterial strain was isolated from a plastic-polluted landfill and identified as Paenarthrobacter ureafaciens PB10 by 16S rRNA gene sequence-based homology. The strain was found to develop a distinct transparent halo zone around grown colonies on an agar plate supplemented with DBP. The addition of yeast extract (100 mg/L) as a nutrient source accelerated cell biomass production and DBP degradation rate; however, the presence of glucose suppressed DBP degradation by the PB10 strain without affecting its ability to proliferate. The strain PB10 was efficient in eliminating DBP under various pH conditions (5.0-8.0). Maximum cell growth and degradation of 99.49% at 300 mg/L DBP were achieved in 72 h at the optimized mineral salt medium (MS) conditions of pH 7.0 and 32 °C. Despite that, when the concentration of DBP rose to 3000 mg/L, the DBP depletion rate was measured at 79.34% in 72 h. Some novel intermediate metabolites, like myristic acid, hexadecanoic acid, stearic acid, and the methyl derivative of 4-hydroxyphenyl acetate, along with monobutyl phthalate and phthalic acid, were detected in the downstream degradation process of DBP through GC-MS profiling. Furthermore, in synchronization with native soil microbes, this PB10 strain successfully removed a notable amount of DBP (up to 54.11%) from contaminated soil under microcosm study after 10 d. Thus, PB10 has effective DBP removal ability and is considered a potential candidate for bioremediation in DBP-contaminated sites.


Assuntos
Dibutilftalato , Micrococcaceae , Ácidos Ftálicos , Dibutilftalato/metabolismo , Biodegradação Ambiental , Ácido Mirístico , RNA Ribossômico 16S/genética , Ácidos Ftálicos/metabolismo , Solo
5.
Asian Pac J Cancer Prev ; 24(11): 3795-3804, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38019237

RESUMO

BACKGROUND: Oxidative stress combined with nullity of xenobiotic metabolizing GSTT1/GSTM1/CYP2E1 genes may increase the susceptibility of agricultural workers to adverse health effects including cancer. The present study was conducted to determine; the prevalence of polymorphisms in GSTM1, GSTT1 and CYP2E1 genes, serum 8-hydroxy-2'-deoxygunosine levels, and the role of these markers in risk of cancer among agricultural workers occupationally exposed to pesticides. METHODS: A total of 360 participants, of which 180 belonging to farming group diagnosed with leukemia (n=60), lymphoma (n=60) and breast cancers (n=60), 90 in non-farming group diagnosed with similar cancers and the other 90 as healthy controls with neither history of occupational exposure nor diagnosed with any type of cancers were recruited. Following the questionnaire survey, serum 8-OHdG and genetic polymorphisms in the three genes were determined using ELISA and PCR methods respectively. RESULTS: The results of the study revealed that farm workers carrying GSTT1 null genotype had increased risk for lymphoma (OR = 5.34; 95% CI = 1.80-15.82) and breast cancer (OR=4.04; 95% CI = 1.24-13.07). For farm workers carrying GSTM1 null genotype, the risk was six-fold for breast cancer (OR = 6.88; 95% CI =1.88-25.99). Further, there found a significant difference between 8-OHdG and nullity of CYP2E1 among the farm workers diagnosed with leukemia. CONCLUSION: The findings of the present study suggest that the polymorphisms in detoxifying genes among farm workers occupationally exposed to pesticides and the oxidative stress may likely be responsible for triggering the mechanism of malignancy.


Assuntos
Neoplasias da Mama , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Leucemia , Linfoma , Praguicidas , Humanos , Feminino , Fazendeiros , Praguicidas/efeitos adversos , Citocromo P-450 CYP2E1/genética , Xenobióticos , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Polimorfismo Genético/genética , 8-Hidroxi-2'-Desoxiguanosina
6.
Diagn Cytopathol ; 51(11): E314-E316, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37540041

RESUMO

Chordoid glioma is an uncommon low-grade glioma and is a CNS WHO grade 2 tumour in the current WHO 2021 classification. Predominantly it is seen in the third ventricle and in young adults. Although the histological features of chordoid glioma are well documented, there is sparse literature describing its cytological features. Here we describe the squash cytological features of a case of chordoid glioma along with summary of prior published cases. The smears tend to be quite cellular, the cells show mild pleomorphism, anisonucleosis, and absent mitotic activity. The background shows a distinctive bluish myxoid stroma. It can be mistaken for high grade glioma on squash cytology.


Assuntos
Neoplasias do Ventrículo Cerebral , Glioma , Terceiro Ventrículo , Adulto Jovem , Humanos , Glioma/patologia , Neoplasias do Ventrículo Cerebral/patologia , Terceiro Ventrículo/patologia , Citodiagnóstico , Imageamento por Ressonância Magnética
7.
Mol Microbiol ; 2023 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-37424153

RESUMO

It is interesting to identify factors involved in the regulation of the encystation of Entamoeba histolytica that differentiate trophozoites into cysts. Evolutionarily conserved three amino acid loop extension (TALE) homeodomain proteins act as transcription factors and execute a variety of functions that are essential for life. A TALE homeodomain (EhHbox) protein-encoding gene has been identified in E. histolytica (Eh) that is highly upregulated during heat shock, glucose, and serum starvation. Its ortholog, EiHbox1, a putative homeobox protein in E. invadens (Ei), is also highly upregulated during the early hours of encystation, glucose starvation, and heat shock. They belong to the PBX family of TALE homeobox proteins and have conserved residues in the homeodomain that are essential for DNA binding. Both are localized in the nucleus during encystation and under different stress conditions. The electrophoretic mobility shift assay confirmed that the recombinant GST-EhHbox binds to the reported TGACAG and TGATTGAT motifs. Down-regulation of EiHbox1 by gene silencing reduced Chitin synthase, Jacob, and increased Jessie gene expression, resulting in defective cysts and decreased encystation efficiency and viability. Overall, our results suggest that the TALE homeobox family has been conserved during evolution and acts as a transcription factor to control the differentiation of Entamoeba by regulating the key encystation-induced genes.

8.
Front Cell Infect Microbiol ; 13: 1134036, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37434784

RESUMO

Tuberculosis (TB) is one of the oldest human diseases and is one of the major causes of mortality and morbidity across the Globe. Mycobacterium tuberculosis (Mtb), the causal agent of TB is one of the most successful pathogens known to mankind. Malnutrition, smoking, co-infection with other pathogens like human immunodeficiency virus (HIV), or conditions like diabetes further aggravate the tuberculosis pathogenesis. The association between type 2 diabetes mellitus (DM) and tuberculosis is well known and the immune-metabolic changes during diabetes are known to cause increased susceptibility to tuberculosis. Many epidemiological studies suggest the occurrence of hyperglycemia during active TB leading to impaired glucose tolerance and insulin resistance. However, the mechanisms underlying these effects is not well understood. In this review, we have described possible causal factors like inflammation, host metabolic changes triggered by tuberculosis that could contribute to the development of insulin resistance and type 2 diabetes. We have also discussed therapeutic management of type 2 diabetes during TB, which may help in designing future strategies to cope with TB-DM cases.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Resistência à Insulina , Tuberculose , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Incidência , Tuberculose/complicações , Tuberculose/epidemiologia
9.
Urology ; 180: 1-8, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37331485

RESUMO

OBJECTIVE: To conduct a systematic review and meta-analysis comparing microwave ablation (MWA) and cryoablation for renal cell carcinoma (RCC). METHODS: The systematic search was performed in MEDLINE, Embase, and Cochrane databases. Studies published in English from January 2006 to February 2022 that assessed adults with primary RCC who received MWA or cryoablation were included. Study arms from RCTs, comparative observational, and single-arm studies were eligible. The outcomes included local tumor recurrence (LTR), overall survival, disease-free survival, overall/major complications, procedure/ablation time, 1- to 3-month primary technique efficacy, and technical success. Single-arm meta-analyses were performed using the random effects model. Sensitivity analyses excluding low-quality studies assessed using the MINORs scale were performed. Univariable and multivariable examined the effects of prognostic factors. RESULTS: Baseline characteristics were similar between groups and mean tumor size for MWA and cryoablation were 2.74 and 2.69 cm. Single-arm meta-analyses were similar for LTR and secondary outcomes between cryoablation and MWA. Ablation time was significantly shorter with MWA than with cryoablation (meta-regression weighted mean difference 24.55 minutes, 95% confidence interval -31.71, -17.38, P < .0001). One-year LTR was significantly lower with MWA than cryoablation (odds ratio 0.33, 95% confidence interval 0.10-0.93, P = .04). There were no significant differences for other outcomes. CONCLUSION: MWA provides significantly improved 1-year LTR and ablation time compared with cryoablation for patients with RCC. Other outcomes appeared similar or favorable for MWA; however, results were not statistically significant. MWA of primary RCC is as safe and effective as cryoablation, which should be confirmed with future comparative studies.


Assuntos
Carcinoma de Células Renais , Ablação por Cateter , Criocirurgia , Neoplasias Renais , Adulto , Humanos , Carcinoma de Células Renais/cirurgia , Criocirurgia/métodos , Micro-Ondas/uso terapêutico , Resultado do Tratamento , Neoplasias Renais/cirurgia , Ablação por Cateter/métodos , Estudos Retrospectivos
10.
Lung Cancer ; 182: 107259, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37321074

RESUMO

RATIONALE: Stereotactic body radiation therapy (SBRT) is the standard of care for inoperable early stage non-small cell lung cancer (NSCLC). Use of image guided thermal ablation (IGTA; including microwave ablation [MWA] and radiofrequency ablation [RFA]) has increased in NSCLC, however there are no studies comparing all three. OBJECTIVE: To compare the efficacy of IGTA (including MWA and RFA) and SBRT for the treatment of NSCLC. METHODS: Published literature databases were systematically searched for studies assessing MWA, RFA, or SBRT. Local tumor progression (LTP), disease-free survival (DFS), and overall survival (OS) were assessed with single-arm pooled analyses and meta-regressions in NSCLC patients and a stage IA subgroup. Study quality was assessed with a modified methodological index for non-randomized studies (MINORS) tool. RESULTS: Forty IGTA study-arms (2,691 patients) and 215 SBRT study-arms (54,789 patients) were identified. LTP was lowest after SBRT at one and two years in single-arm pooled analyses (4% and 9% vs. 11% and 18%) and at one year in meta-regressions when compared to IGTA (OR = 0.2, 95%CI = 0.07-0.63). MWA patients had the highest DFS of all treatments in single-arm pooled analyses. In meta-regressions at two and three-years, DFS was significantly lower for RFA compared to MWA (OR = 0.26, 95%CI = 0.12-0.58; OR = 0.33, 95%CI = 0.16-0.66, respectively). OS was similar across modalities, timepoints, and analyses. Older age, male patients, larger tumors, retrospective studies, and non-Asian study region were also predictors of worse clinical outcomes. In high-quality studies (MINORS score ≥ 7), MWA patients had better clinical outcomes than the overall analysis. Stage IA MWA patients had lower LTP, higher OS, and generally lower DFS, compared to the main analysis of all NSCLC patients. CONCLUSIONS: NSCLC patients had comparable outcomes after SBRT and MWA, which were better than those with RFA.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Ablação por Cateter , Neoplasias Hepáticas , Neoplasias Pulmonares , Radiocirurgia , Humanos , Masculino , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Ablação por Cateter/métodos
11.
J Biol Chem ; 299(5): 104662, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36997086

RESUMO

To chemically modulate the ubiquitin-proteasome system for the degradation of specific target proteins is currently emerging as an alternative therapeutic modality. Earlier, we discovered such properties of the stem cell-supporting small molecule UM171 and identified that members of the CoREST complex (RCOR1 and LSD1) are targeted for degradation. UM171 supports the in vitro propagation of hematopoietic stem cells by transiently perturbing the differentiation-promoting effects of CoREST. Here, we employed global proteomics to map the UM171-targeted proteome and identified the additional target proteins, namely RCOR3, RREB1, ZNF217, and MIER2. Further, we discovered that critical elements recognized by Cul3KBTBD4 ligase in the presence of UM171 are located within the EGL-27 and MTA1 homology 2 (ELM2) domain of the substrate proteins. Subsequent experiments identified conserved amino acid sites in the N-terminus of the ELM2 domain that are essential for UM171-mediated degradation. Overall, our findings provide a detailed account on the ELM2 degrome targeted by UM171 and identify critical sites required for UM171-mediated degradation of specific substrates. Given the target profile, our results are highly relevant in a clinical context and point towards new therapeutic applications for UM171.


Assuntos
Proteínas de Transporte , Proteínas Culina , Células-Tronco Hematopoéticas , Domínios Proteicos , Proteínas Quinases , Proteólise , Diferenciação Celular/efeitos dos fármacos , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise/efeitos dos fármacos , Especificidade por Substrato , Ubiquitina/metabolismo , Proteínas Culina/metabolismo , Proteínas de Transporte/metabolismo , Proteínas Quinases/química
12.
World J Urol ; 41(1): 235-240, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36401135

RESUMO

PURPOSE: To describe trends and patterns of initial percutaneous nephrolithotomy (PCNL) and subsequent procedures from 2010 to 2019 among commercially-insured US adults with urinary system stone disease (USSD). METHODS: Retrospective study of administrative data from the IBM® MarketScan® Database. Eligible patients were aged 18-64 years and underwent PCNL between 1/1/2010 and 12/31/2019. Measures of interest for analysis of trends and patterns included the setting of initial PCNL (inpatient vs. outpatient), percutaneous access (1 vs. 2-step), and the incidence, time course, and type of subsequent procedures (extracorporeal shockwave lithotripsy [SWL], ureteroscopy [URS], and/or PCNL) performed up-to 3 years after initial PCNL. RESULTS: A total of 8,348 patients met the study eligibility criteria. During the study period, there was a substantial shift in the setting of initial PCNL, from 59.9% being inpatient in 2010 to 85.3% being outpatient by 2019 (P < 0.001). The proportion of 1 vs. 2-step initial PCNL fluctuated over time, with a low of 15.1% in 2016 and a high of 22.0% in 2019 but showed no consistent yearly trend (P = 0.137). The Kaplan-Meier estimated probability of subsequent procedures following initial PCNL was 20% at 30 days, 28% at 90 days, and 50% at 3 years, with slight fluctuations by initial PCNL year. From 2010 to 2019, the proportion of subsequent procedures accounted for by URS increased substantially (from 30.8 to 51.8%), whereas SWL decreased substantially (from 39.5 to 14.7%) (P < 0.001). CONCLUSIONS: From 2010 to 2019, PCNL procedures largely shifted to the outpatient setting. Subsequent procedures after initial PCNL were common, with most occurring within 90 days. URS has become the most commonly-used subsequent procedure type.


Assuntos
Seguro Saúde , Nefrolitotomia Percutânea , Cálculos Urinários , Adulto , Humanos , Litotripsia/estatística & dados numéricos , Litotripsia/tendências , Nefrolitotomia Percutânea/estatística & dados numéricos , Nefrolitotomia Percutânea/tendências , Nefrostomia Percutânea/estatística & dados numéricos , Nefrostomia Percutânea/tendências , Estudos Retrospectivos , Ureteroscopia/estatística & dados numéricos , Ureteroscopia/tendências , Cálculos Urinários/cirurgia , Estados Unidos , Seguro Saúde/estatística & dados numéricos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade
13.
Biochem Biophys Res Commun ; 640: 125-133, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36502628

RESUMO

Rab GTPases are known for controlling intracellular membrane traffic in a GTP-dependent manner. Rab7l1, belonging to family of Rab GTPases, is important for both endosomal sorting and retrograde transport. In our previous study, we identified a novel role of Rab7l1 in phagosome maturation. However, its role in regulating macrophage innate-effector signaling and cytokine response is not clearly understood. In this study, we have demonstrated that upon treatment of Rab7l1-knocked-down (Rab7l1-KD) THP-1 macrophages with lipopolysaccharide (LPS) and Pam3CSK4 has led to higher induction levels of tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) as compared to the control cells that received scrambled shRNA. Similar results were observed in Rab7l1-KD RAW 264.7 and Balb/c peritoneal macrophages. The phospho-ERK 1/2 (extracellular signal-regulated kinase 1/2) and phospho-p38 MAPK (mitogen-activated protein kinase) levels, known to be responsible for higher induction of TNF-α and IL-10 respectively, were higher in Rab7l1-KD THP-1 macrophages which also displayed higher nuclear translocation of p50/p65 nuclear factor kappa B (NF-κB) upon stimulation with LPS. Surface expression levels of toll-like receptor 2 (TLR2), TLR4 and CD14 receptors were higher in Rab7l1-KD THP-1 macrophages as compared to the control cells. However, intracellular levels of these receptors were lower in Rab7l1-KD THP-1 macrophages as compared to the control group. Together, our study suggests that Rab7l1 has a role in regulating MAPK signaling and cytokine effector responses in macrophages by regulating the surface expression of membrane receptors.


Assuntos
Interleucina-10 , Receptores Toll-Like , Proteínas rab de Ligação ao GTP , Citocinas/metabolismo , Interleucina-10/metabolismo , Lipopolissacarídeos , Macrófagos/metabolismo , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Receptores Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Humanos , Animais , Camundongos
14.
Pathogens ; 13(1)2023 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-38251328

RESUMO

The "Wattle and Daub" model of cyst wall formation in Entamoeba invadens has been used to explain encystment in Entamoeba histolytica, the causal agent of amoebiasis, and this process could be a potential target for new antiamoebic drugs. In this study, we studied the morphological stages of chitin wall formation in E. invadens in more detail using fluorescent chitin-binding dyes and the immunolocalization of cyst wall proteins. It was found that chitin deposition was mainly initiated on the cell surface at a specific point or at different points at the same time. The cystic wall grew outward and gradually covered the entire surface of the cyst over time, following the model of Wattle and Daub. The onset of chitin deposition was guided by the localization of chitin synthase 1 to the plasma membrane, occurring on the basis of the Jacob lectin in the cell membrane. During encystation, F-actin was reorganized into the cortical region within the early stages of encystation and remained intact until the completion of the chitin wall. The disruption of actin polymerization in the cortical region inhibited proper wall formation, producing wall-less cysts or cysts with defective chitin walls, indicating the importance of the cortical actin cytoskeleton for proper cyst wall formation.

15.
Mol Biochem Parasitol ; 251: 111507, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35870645

RESUMO

Starvation is always accompanied by an increase in the ratio of AMP/ATP followed by activation of AMPK. It is one of the sensors for cellular energy status and is highly conserved across various species. Its role in the stage differentiation process of protozoan species like Giardia, Plasmodium, Trypanosome, and Toxoplasma has been reported. Since Entamoeba undergoes encystation in glucose-starved conditions; it intrigued us to investigate the existence and role of AMPK during the differentiation of trophozoites to the cyst. By employing in silico approaches, we have identified an AMPK homologue which is denominated here as EiAMPK (AMPK-like protein in Entamoeba invadens). Sequence and structural analysis indicate that EiAMPK is sequentially and structurally similar to the AMPK alpha subunit of other organisms. The recombinant form of EiAMPK was functionally active and in accordance, its activity was inhibited by an AMPK-specific inhibitor (eg. Compound C). The increased expression of EiAMPK during different stresses indicated that EiAMPK is a stress-responsive gene. To further investigate, whether EiAMPK has any role in encystation, we employed RNAi-mediated gene silencing that demonstrated its active involvement in encystation. It is known that Entamoeba maintains a flow of glucose from the glycolytic pathway to chitin synthesis for cyst wall formation during encystation. It is conceivable that EiAMPK might have a command over such glucose metabolism. As anticipated, the chitin synthesis was found greatly inhibited in both EiAMPK knockdown and Compound C treated cells, indicating that EiAMPK regulates the cyst wall chitin synthesis.


Assuntos
Entamoeba , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Adenilato Quinase/metabolismo , Quitina , Entamoeba/genética , Entamoeba/metabolismo , Glucose/metabolismo
16.
J Am Coll Radiol ; 19(10): 1121-1129, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35738412

RESUMO

OBJECTIVE: To provide recent population-based estimates of transthoracic needle biopsy (TTNB) complications and risk factors associated with these complications. METHODS: This retrospective cohort analysis included adults from a nationally representative longitudinal insurance claims data set who underwent TTNB in 2017 or 2018. Complications that were evaluated included pneumothorax, hemorrhage, and air embolism. Separate logistic regression models estimated the association of pneumothorax or hemorrhage with the setting of care (ie, inpatient or outpatient) and selected baseline patient demographic and clinical characteristics including age, gender, history of chronic obstructive pulmonary disease, diagnosis of pleural effusion, tobacco use, use of oral anticoagulants and antiplatelet agents, prior lung cancer screening, previous bronchoscopy within 1 year, and Elixhauser comorbidity index. RESULTS: Among 16,971 patients who underwent TTNB, 25.8% experienced a complication within 3 days of the procedure (pneumothorax 23.3%, hemorrhage 3.6%, and air embolism 0.02%). Among patients who experienced pneumothorax, 31.9% required chest tube drainage. Among patients undergoing an outpatient TTNB (n = 12,443), 6.9% were hospitalized within 7 days. Biopsy in an inpatient setting, chronic obstructive pulmonary disease diagnosis, and prior bronchoscopy were associated with higher rates of both pneumothorax and hemorrhage. Prior lung cancer screening was associated with an increased risk of pneumothorax, and prior use of oral anticoagulants or antiplatelets was associated with higher rates of hemorrhage. CONCLUSION: This contemporary population-based cohort study demonstrated that approximately one-quarter of patients undergoing TTNB experienced a complication. Pneumothorax was the most frequent complication, and hemorrhage and air embolism were rare. Among outpatients, complications from TTNB are an important cause of hospitalization.


Assuntos
Embolia Aérea , Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Pneumotórax , Doença Pulmonar Obstrutiva Crônica , Adulto , Anticoagulantes/uso terapêutico , Biópsia por Agulha/efeitos adversos , Biópsia por Agulha/métodos , Estudos de Coortes , Detecção Precoce de Câncer/efeitos adversos , Embolia Aérea/complicações , Embolia Aérea/patologia , Hemorragia/etiologia , Hemorragia/patologia , Humanos , Biópsia Guiada por Imagem/métodos , Pulmão , Neoplasias Pulmonares/patologia , Nódulos Pulmonares Múltiplos/patologia , Inibidores da Agregação Plaquetária , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/patologia , Estudos Retrospectivos , Fatores de Risco
17.
Cureus ; 14(4): e23809, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35518519

RESUMO

Introduction Malignancy, tuberculosis, and non-tubercular pleural infections account for most exudative pleural effusion. Pleural fluid cytology, biochemical tests and even pleural fluid cell block studies may fail to yield a diagnosis in certain cases. Medical thoracoscopy is the gold standard for the diagnosis of unexplained pleural effusions. However, access to medical thoracoscopy may be limited, particularly in developing countries. Also, certain patients may not be fit to undergo the procedure because of medical conditions. An ultrasound-guided pleural biopsy is an option in such conditions. The present study is intended to compare the diagnostic yield and complications of both methods of pleural biopsy in undiagnosed exudative pleural effusion under a randomized controlled trial. Method After fulfilling all the inclusion criteria, participants were randomized to either ultrasound-guided closed pleural biopsy or thoracoscopic-guided pleural biopsy groups. The primary outcome was to compare the diagnostic yield of ultrasound-guided Tru-Cut® (Newtech Medical Devices, Faridabad, India) closed pleural biopsy versus thoracoscopic pleural biopsy, and the secondary outcomes were to compare the complications rate, duration of the procedure, and hospital stay in the patients undergoing ultrasound-guided pleural biopsy versus thoracoscopic pleural biopsy, and predictors of a positive biopsy result in both groups. Result A total of 118 patients with pleural effusion were screened; 39 of them who were eligible, randomized into the ultrasound group (20 patients) and the thoracoscopic group (19 patients). The median age of participants was 53.5 (50-58) years and 55 (45-64) years in the ultrasound and thoracoscopic groups, respectively. Pleural fluid cell count, protein, adenosine deaminase (ADA), and lactate dehydrogenase (LDH) were similar in both groups, although pleural fluid glucose was low in the ultrasound group. Diagnostic yield was 90% (18/20) and 94.7% (18/19) in the ultrasound and thoracoscopic groups, respectively, which was statistically non-significant (p=0.963). The median duration of hospital stay was 9.5 (5.3-27) days and 15 (12-22) days in ultrasound and thoracoscopic groups respectively. The thoracoscopic group had a more prolonged stay compared to the ultrasound group, but it was statistically non-significant (p=0.09). The duration of the procedure was significantly longer in the thoracoscopic group 90 (85-105) minutes, in comparison to ultrasound 47.5 (41.3-55) minutes (p=0.001). No major complications were seen in both groups. Subcutaneous emphysema was the most common complication in the thoracoscopic group (10%), followed by hemorrhage (5.3%), and respiratory failure (5.3%). Hypotension was the only complication in the ultrasound group (5%). The rate of complications was significantly higher in the thoracoscopic group (p<0.01). Conclusion Ultrasound-guided closed pleural biopsy is as good as thoracoscopic pleural biopsy in undiagnosed exudative pleural effusion. It was associated with a shorter procedure duration, a shorter hospital stay, and fewer complications as compared to thoracoscopic biopsy. Both the procedures were safe in experienced hands and a hospital setup, but the thoracoscopic pleural biopsy was associated with complications.

18.
BMJ Case Rep ; 15(3)2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241448

RESUMO

Polymyositis is an immune-mediated inflammatory myopathy usually presenting with weakness of proximal muscles in a symmetric pattern. Generalised subcutaneous oedema as presenting feature of inflammatory myopathy, especially polymyositis, has rarely been reported. We report here a case of a young woman who was admitted to our facility with generalised severe subcutaneous oedema. During hospital stay, she gradually developed significant proximal muscle weakness with bulbar symptoms. The initial presentation of the patient masqueraded with other causes of anasarca. However, detailed clinical features, laboratory evaluation, electromyography and muscle biopsy clinched the diagnosis of polymyositis. She was treated with systemic corticosteroids and azathioprine. The patient responded well to treatment and the swelling gradually subsided.


Assuntos
Miosite , Polimiosite , Azatioprina/uso terapêutico , Edema/complicações , Feminino , Humanos , Debilidade Muscular/tratamento farmacológico , Debilidade Muscular/etiologia , Miosite/complicações , Miosite/diagnóstico , Miosite/tratamento farmacológico , Polimiosite/diagnóstico
19.
Curr Res Microb Sci ; 3: 100101, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35024643

RESUMO

In agricultural soil, cadmium (Cd) pollution compromises soil health, reduces crop yield, and produces Cd-contaminated crops. Bio-based approaches are necessary as an eco-friendly and sustainable solution to mitigate Cd-polluted areas. A heavy metal-resistant rhizobacterial strain (AS10) has been isolated from a heavy metal-defiled rice field. The 16S rDNA sequence and MALDI-TOF MS analyses of ribosomal protein reveal its identity closely similar to Enterobacter cloacae. The strain was found to withstand up to 4000 µg/ml Cd2+, 3312 µg/ml Pb2+ and 1500 µg/ml As3+. The Cd2+ removal efficiency was recorded as high as 72.11% when grown in 4000 µg/ml Cd2+. The strain's Cd-accumulation efficiency was also apprehended by TEM-EDAX followed by XRD-XRF-FTIR analyses. Besides, the strain showed solubilization of inorganic phosphate, ACC deaminase activity, nitrogen fixation and IAA production ability. Added further, the strain, as an efficient bioinoculant, significantly improved rice plant growth at the seedling stage through Cd immobilization. It prevented the surge of stress ethylene and oxidative stress in rice seedlings, resulting in overall plant growth improvement. Hence, the strain AS10 as potent plant growth-promoting rhizobacteria (PGPR) may be beneficial, especially in heavy metal-contaminated crop fields.

20.
Lung India ; 39(1): 80-81, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34975059

RESUMO

A 39-year-old nonsmoker male presented with complaints of cough with recurrent mild hemoptysis. Computed tomography of thorax showed nodular lesions on the right lateral wall of trachea. Fiber-optic bronchoscopy revealed multiple nodular lesions on the right lateral wall of lower one-third of trachea. Histopathological examination of biopsy specimen from the nodules was suggestive of tracheobronchopathia osteochondroplastica which is an uncommon airway disorder.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA