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1.
Ann Surg Oncol ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38954091

RESUMEN

BACKGROUND: Invasive lobular carcinoma (ILC) is the second most common subtype of breast cancer. Although mammography is known to have low sensitivity for ILC, there are no data to guide the optimal surveillance after treatment. We explored surveillance strategies after breast-conserving surgery (BCS) for ILC and determined the proportion of imaging-detected recurrences versus interval cancers. METHODS: From an institutional database of 813 women, we retrospectively identified patients who underwent BCS for stage I-III ILC and subsequently had a recurrence. We categorized patients by surveillance strategy and determined the modality of recurrence detection. Interval cancer rates for local recurrences were compared across surveillance strategies using the Chi-square test. We evaluated overall survival with the log-rank test and a Cox proportional hazards model. RESULTS: We included 58 patients with ILC who had a recurrence after BCS. Of these, 22 (37.9%) had local recurrence, 27 (46.6%) had distant recurrence, and 9 (15.5%) had both local and distant recurrence. Most patients underwent routine mammographic surveillance (65.2%), with 19.6% having supplemental breast magnetic resonance imaging (MRI) and 15.2% having no surveillance. The interval cancer rate was significantly higher in the mammographic surveillance group compared with the MRI surveillance group (61.9% vs. 16.7%; p < 0.001). CONCLUSION: In this study of patients with recurrence after BCS for primary treatment of stage I-III ILC, we found that most local recurrences were not detected by surveillance mammography. These data support further investigation of supplemental imaging beyond mammography specifically for patients with ILC who undergo BCS.

2.
Cureus ; 16(4): e58540, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38957831

RESUMEN

The aim of this meta-analysis was to determine the effect of pulmonary hypertension (PH) on survival in patients undergoing transcatheter aortic valve replacement (TAVR). The present study was conducted according to the guidelines of Preferred Reporting of Systematic Review and Meta-Analysis (PRISMA). We conducted a comprehensive search of electronic databases including PubMed/MEDLINE, Embase, Cochrane Library, and Web of Science from January 1, 2015, to March 10, 2024. Outcomes assessed in this meta-analysis included early and late all-cause mortality and cardiovascular mortality. Total 15 studies were integrated into the pooled analysis to assess the impact of PH on outcomes among patients undergoing TAVR, comprising a total sample size of 35,732 individuals. The pooled prevalence of PH stood at 52.57% (n=18,767). Predominantly, the studies were conducted in the United States (n=6), followed by Germany (n=3), with one study each from Japan, Italy, Switzerland, Brazil, Poland, and Australia. Pooled analysis showed that risk of short-term mortality was greater in patients with PH compared to patients without PH (risk ratio (RR): 1.46, 95% CI: 1.19 to 1.80). Risk of long-term mortality was greater in patients with PH (RR: 1.42, 95% CI: 1.29 to 1.55). Risk of cardiovascular mortality was also greater in patients with PH compared to patients without PH (RR: 1.66, 95% CI: 1.36 to 2.02). We advocate for further research to address gaps in understanding different types of PH and their impacts on mortality and cardiovascular outcomes.

3.
Cureus ; 16(6): e61526, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38957250

RESUMEN

Type 2 diabetes mellitus is a metabolic condition where vascular inflammation and oxidative stress contribute to disease progression and associated complications. Although statins are recommended for managing dyslipidemia in diabetes, additional therapies are often required to achieve target lipid levels. This meta-analysis aimed to evaluate the efficacy of rosuvastatin monotherapy versus combination therapy with ezetimibe in patients with type 2 diabetes. A systematic literature search was conducted across multiple databases until April 2024, identifying six randomized controlled trials meeting the inclusion criteria. The meta-analysis revealed that the rosuvastatin plus ezetimibe combination resulted in significantly greater reductions in total cholesterol (mean difference, or MD: 19.49; 95% CI: 13.99 to 24.99), triglycerides (MD: 13.44; 95% CI: 2.04 to 24.85), and low-density lipoprotein cholesterol (MD: -17.68; 95% CI: 12.85 to 22.51) compared to rosuvastatin monotherapy. Conversely, rosuvastatin monotherapy achieved a greater reduction in HbA1c levels (MD: -0.11; 95% CI: -0.17 to -0.04). Subgroup analysis demonstrated that using the same dose of rosuvastatin in both groups led to more significant improvements in lipid parameters with lower heterogeneity. The findings suggest that the rosuvastatin-ezetimibe combination may be a more effective lipid-lowering strategy for patients with type 2 diabetes, though larger studies are needed to assess long-term safety and optimal dosing. Additionally, while rosuvastatin monotherapy provided modest HbA1c reductions, the clinical relevance remains uncertain, and potential risks with high-dose statins should be considered.

4.
Pathol Res Pract ; 260: 155424, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38909406

RESUMEN

Breast cancer is one of the most common causes of cancer-related mortality globally, and its aggressive phenotype results in poor treatment outcomes. Growth Arrest-Specific 5 long non-coding RNA has attracted considerable attention due to its pivotal function in apoptosis regulation and tumor aggressiveness in breast cancer. Gas5 enhances apoptosis by regulating apoptotic proteins, such as caspases and BCL2 family proteins, and the sensitivity of BCCs to chemotherapeutic agents. At the same time, low levels of GAS5 increased invasion, metastasis, and overall tumor aggressiveness. GAS5 also regulates EMT markers, critical for cancer metastasis, and influences tumor cell proliferation by regulating various signaling components. As a result, GAS5 can be restored to suppress tumor development as a possible therapeutic strategy, which might present promising prospects for a patient's treatment. Its activity levels might also be a crucial indicator and diagnostic parameter for prediction. This review highlights the significant role of GAS5 in modulating apoptosis and tumor aggressiveness in breast cancer, emphasizing its potential as a therapeutic target for breast cancer treatment and management.

5.
Cureus ; 16(5): e60086, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38860078

RESUMEN

Anthracyclines are effective chemotherapeutic agents widely used to treat various cancers, but their use is limited by the risk of cardiotoxicity and heart failure. While strategies like dose reduction have been explored, there are no well-established therapies to mitigate this risk. Emerging evidence suggests sodium-glucose cotransporter 2 inhibitors (SGLT2i) may have cardioprotective effects, providing a rationale for investigating their potential utility in anthracycline-treated patients. We conducted a systematic review and meta-analysis to synthesize available evidence on the efficacy of SGLT2i in reducing heart failure incidence and mortality in patients undergoing anthracycline-based cancer therapy. Relevant studies were identified through comprehensive database searches and screened based on predefined criteria. Data extraction and quality assessment were performed independently by two reviewers. Four observational studies, encompassing 5,590 patients, were included. The pooled analysis showed a higher but non-significant risk of developing heart failure in the non-SGLT2i group compared to the SGLT2i group (RR = 0.67, 95% CI: 0.40-1.41). The risk of all-cause mortality was significantly lower in patients receiving SGLT2i (RR = 0.55, 95% CI: 0.39-0.77). This meta-analysis suggests SGLT2i are associated with a lower risk of mortality and heart failure incidence in anthracycline-treated patients, although larger studies are needed to confirm these findings. The mechanisms underlying these potential benefits require further elucidation. Despite limitations, this analysis highlights the promising role of SGLT2i as a cardioprotective strategy in this high-risk population.

6.
Cell Biochem Biophys ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38916791

RESUMEN

Conventional cancer therapies can have significant adverse effects as they are not targeted to cancer cells and may damage healthy cells. Single-stranded oligonucleotides assembled in a particular architecture, known as aptamers, enable them to attach selectively to target areas. Usually, they are created by Systematic Evolution of Ligand by Exponential enrichment (SELEX), and they go through a rigorous pharmacological revision process to change their therapeutic half-life, affinity, and specificity. They could thus offer a viable substitute for antibodies in the targeted cancer treatment market. Although aptamers can be a better choice in some situations, antibodies are still appropriate for many other uses. The technique of delivering aptamers is simple and reasonable, and the time needed to manufacture them is relatively brief. Aptamers do not require animals or an immune response to be produced, in contrast to antibodies. When used as a medication, aptamers can directly suppress tumor cells. As an alternative, they can be included in systems for targeted drug delivery that administer medications specifically to tumor cells while reducing toxicity to healthy cells. The most recent and cutting-edge methods for treating gastrointestinal (GI) tract cancer with aptamers will be covered in this review, with a focus on targeted therapy as a means of conquering resistance to traditional medicines.

7.
SLAS Technol ; 29(4): 100159, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38909655

RESUMEN

In today's digital world, with growing population and increasing pollution, unhealthy lifestyle habits like irregular eating, junk food consumption, and lack of exercise are becoming more common, leading to various health problems, including kidney issues. These factors directly affect human kidney health. To address this, we require early detection techniques that rely on text data. Text data contains detailed information about a patient's medical history, symptoms, test results, and treatment plans, giving a complete picture of kidney health and enabling timely intervention. In this research paper, we proposed a range of sophisticated models, such as Gradient Boosting Classifier, Light GBM, CatBoost, Support Vector Classifier (SVC), Random Boost, Logistic Regression, XGBoost, Deep Neural Network (DNN), and an Improved DNN. The Improved DNN demonstrated exceptional performance, with an accuracy of 90 %, precision of 89 %, recall of 90 %, and an F1-Score of 89.5 %. By combining traditional machine learning and deep neural networks, this integrative approach enables the identification of intricate patterns in datasets. The model's data-driven processes consistently update internal parameters, guaranteeing flexibility in response to evolving healthcare settings. This research represents a notable advancement in the progress of creating a more detailed and individualised ability to diagnose kidney stones, which could potentially lead to better clinical results and patient treatment.

8.
Cell Biochem Biophys ; 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38907940

RESUMEN

Exosomes are the primary category of extracellular vesicles (EVs), which are lipid-bilayer vesicles with biological activity spontaneously secreted from either normal or tansformed cells. They serve a crucial role for intercellular communication and affect extracellular environment and the immune system. Tumor-derived exosomes (TEXs) enclose high levels of immunosuppressive proteins, including programmed death-ligand 1 (PD-L1). PD-L1 and its receptor PD-1 act as crucial immune checkpoint molecules, thus facilitating tumor advancement by inhibiting immune responses. PDL-1 is abundantly present on tumor cells and interacts with PD-1 on activated T cells, resulting in T cell suppression and allowing immune evasion of cancer cells. Various FDA-approved monoclonal antibodies inhibiting the PD-1/PD-L1 interaction are commonly used to treat a diverse range of tumors. Although the achieved results are significant, some individuals have a poor reaction to PD-1/PD-L1 blocking. PD-L1-enriched TEXs may mimic the impact of cell-surface PD-L1, consequently potentiating tumor resistance to PD1/PD-L1 based therapy. In light of this, a strong correlation between circulating exosomal PD-L1 levels and response rate to anti-PD-1/PD-L1 antibody treatment has been evinced. This article inspects the function of exosomal PDL-1 in developing resistance to anti-PD-1/PD-L1 therapy for opening new avenues for overcoming tumor resistance to such modalities and development of more favored combination therapy.

9.
Brain Res ; 1841: 149089, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38880410

RESUMEN

Epilepsy is a prevalent neurological illness which is linked with high worldwide burdens. Oxidative stress (OS) is recognized to be among the contributors that trigger the advancement of epilepsy, affecting neuronal excitability and synaptic transmission. Various types of non-coding RNAs (ncRNAs) are known to serve vital functions in many disease mechanisms, including epilepsy. The current review sought to understand better the mechanisms through which these ncRNAs regulate epilepsy's OS-related pathways. We investigated the functions of microRNAs in controlling gene expression at the post-translatory stage and their involvement in OS and neuroinflammation. We also looked at the different regulatory roles of long ncRNAs, including molecular scaffolding, enhancer, and transcriptional activator, during OS. Circular RNAs and their capability to act as miRNA decoys and their consequential impact on epilepsy development were also explored. Our review aimed to improve the current understanding of novel therapies for epilepsy based on the role of ncRNAs in OS pathways. We also demonstrated the roles of ncRNAs in epilepsy treatment and diagnosis, explaining that these molecules play vital roles that could be used in therapy as biomarkers.

10.
J Inorg Biochem ; 258: 112617, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38805758

RESUMEN

Four Pt(II) bis(pyrrole-imine) Schiff base chelates (1-4) were synthesised by previously reported methods, through a condensation reaction, and the novel crystal structure of 2,2'-{propane-1,3-diylbis[nitrilo(E)methylylidene]}bis(pyrrol-1-ido)platinum(II) (1) was obtained. Pt(II) complexes 1-4 exhibited phosphorescence, with increased luminescence in anaerobic solvents or when bound to human serum albumin (HSA). One of the complexes shows a 15.6-fold increase in quantum yield when bound to HSA and could be used to detect HSA concentrations as low as 5 nM. Pt(II) complexes 1-3 was investigated as potential theranostic agents in MCF-7 breast cancer cells, but only complex 3 exhibited cytotoxicity when irradiated with UV light (λ355nmExcitation). Interestingly, the cytotoxicity of complex 1 was unresponsive to UV light irradiation. This indicates that only complex 3 can be considered a potential photosensitising agent.


Asunto(s)
Pirroles , Humanos , Células MCF-7 , Pirroles/química , Antineoplásicos/farmacología , Antineoplásicos/química , Bases de Schiff/química , Iminas/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/efectos de la radiación , Complejos de Coordinación/síntesis química , Sustancias Luminiscentes/química , Sustancias Luminiscentes/toxicidad , Sustancias Luminiscentes/síntesis química , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo
11.
Pathol Res Pract ; 259: 155346, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38781762

RESUMEN

Osteosarcoma (OS) is a bone cancer which stems from several sources and presents with diverse clinical features, making evaluation and treatment difficult. Chemotherapy tolerance and restricted treatment regimens hinder progress in survival rates, requiring new and creative therapeutic strategies. The Wnt/ß-catenin system has been recognised as an essential driver of OS development, providing potential avenues for therapy. Non-coding RNAs (ncRNAs), such as circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), are essential in modulating the Wnt/ß-catenin cascade in OS. MiRNAs control the system by targeting vital elements, while lncRNAs and circRNAs interact with system genes, impacting OS growth and advancement. This paper thoroughly analyses the intricate interplay between ncRNAs and the Wnt/ß-catenin cascade in OS. We examine how uncontrolled levels of miRNAs, lncRNAs, and circRNAs lead to an abnormal Wnt/ß-catenin network, which elevates the development, spread, and susceptibility to the treatment of OS. We emphasise the potential of ncRNAs as diagnostic indicators and avenues for treatment in OS care. The review offers valuable insights for academics and clinicians studying OS aetiology and creating new treatment techniques for the ncRNA-Wnt/ß-catenin cascade. Utilising the oversight roles of ncRNAs in the Wnt/ß-catenin system shows potential for enhancing the outcomes of patients and progressing precision medicine in OS therapy.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Óseas , Osteosarcoma , ARN no Traducido , Vía de Señalización Wnt , Humanos , Osteosarcoma/genética , Osteosarcoma/patología , Osteosarcoma/metabolismo , Osteosarcoma/tratamiento farmacológico , Vía de Señalización Wnt/genética , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Neoplasias Óseas/metabolismo , Neoplasias Óseas/tratamiento farmacológico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , ARN no Traducido/genética , ARN no Traducido/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Regulación Neoplásica de la Expresión Génica
12.
Environ Toxicol Pharmacol ; 108: 104467, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38763439

RESUMEN

Bisphenol A (BPA) is a ubiquitous industrial chemical used in the production of polycarbonate plastics and epoxy resins, found in numerous consumer products. Despite its widespread use, its potential adverse health effects have raised significant concerns. This review explores the molecular mechanisms and evidence-based literature underlying BPA-induced toxicities and its implications for human health. BPA is an endocrine-disrupting chemical (EDC) which exhibits carcinogenic properties by influencing various receptors, such as ER, AhR, PPARs, LXRs, and RARs. It induces oxidative stress and contributes to cellular dysfunction, inflammation, and DNA damage, ultimately leading to various toxicities including but not limited to reproductive, cardiotoxicity, neurotoxicity, and endocrine toxicity. Moreover, BPA can modify DNA methylation patterns, histone modifications, and non-coding RNA expression, leading to epigenetic changes and contribute to carcinogenesis. Overall, understanding molecular mechanisms of BPA-induced toxicity is crucial for developing effective strategies and policies to mitigate its adverse effects on human health.


Asunto(s)
Compuestos de Bencidrilo , Disruptores Endocrinos , Fenoles , Compuestos de Bencidrilo/toxicidad , Fenoles/toxicidad , Humanos , Disruptores Endocrinos/toxicidad , Animales , Estrés Oxidativo/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Epigénesis Genética/efectos de los fármacos , Contaminantes Ambientales/toxicidad
13.
Cureus ; 16(4): e58019, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38738070

RESUMEN

The aim of this systematic review and meta-analysis was to investigate the impact of early sodium-glucose cotransporter-2 (SGLT2) initiation on long-term cardiovascular outcomes and all-cause mortality among patients with acute coronary syndrome (ACS). For this study, we adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline. Two researchers independently performed a comprehensive literature search on PubMed, Embase, and the Cochrane Library, spanning from the inception of each database to February 24, 2023, without language limitations. The outcomes examined in this meta-analysis comprised major adverse cardiovascular events (MACE) (as defined by individual studies), all-cause mortality, cardiovascular mortality, stroke (ischemic and hemorrhagic), recurrent ACS, and hospitalization due to heart failure (HF). A total of nine studies were included in this meta-analysis. The pooled analysis of nine studies revealed a significant reduction in the risk of MACE, all-cause mortality, cardiovascular mortality, and cardiovascular-related hospitalizations among patients receiving SGLT2 inhibitors (SGLT2i) compared to those in the control group. Additionally, there was a trend toward a lower risk of recurrent ACS in the SGLT2i group, although this difference did not reach statistical significance. The findings of this study suggest a promising therapeutic effect of SGLT2 inhibitors in this population. Further research, particularly focusing on myocardial infarction (MI) patients, is warranted to validate these results and potentially revolutionize ACS management.

14.
Cureus ; 16(4): e57656, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38707166

RESUMEN

The objective of this network meta-analysis was to assess the efficacy and safety of apixaban, dabigatran, rivaroxaban, and edoxaban in patients diagnosed with atrial fibrillation and valvular heart disease. A comprehensive search was conducted across various electronic databases, including PubMed, Embase, and Web of Science, from inception to February 15, 2024. The search strategy utilized a combination of medical subject headings (MeSH) terms and relevant keywords related to valvular heart disease, atrial fibrillation, anticoagulant therapy, and study design, such as randomized controlled trials and observational studies. The outcomes evaluated in this analysis comprised the incidence of stroke or systemic embolism (SE), as well as the occurrences of major bleeding events. A total of 10 studies were incorporated into this meta-analysis, encompassing 40,662 participants. Of these, 12,385 received apixaban, 2,829 received dabigatran, 13,662 received rivaroxaban, 2,582 received edoxaban, and 9,202 received warfarin. The duration of follow-up in the included studies ranged from 3 to 54 months. Among the four direct oral anticoagulants (DOACs) studied, apixaban demonstrated a significant reduction in the risk of stroke or SE when compared to other DOACs and warfarin, highlighting its efficacy in patients with atrial fibrillation and valvular heart disease. Additionally, apixaban exhibited a lower risk of major bleeding events, further emphasizing its favorable safety profile compared to the other agents assessed. In conclusion, our findings suggest that apixaban may be more effective and safer than other DOACs and warfarin in this patient population. However, additional studies are warranted to compare the various DOACs in this cohort to identify the optimal treatment strategy for preventing adverse outcomes.

15.
Artículo en Inglés | MEDLINE | ID: mdl-38716210

RESUMEN

Background: Robotic colorectal resections (RCR) have been gaining popularity recently due to several advantages in addition to oncological safety. The objective of this review is to evaluate the cost comparison of RCR versus laparoscopic colorectal resections (LCR). Methods: All types of comparative studies reporting the cost of RCR versus LCR were retrieved from the search of standard medical electronic databases and analysis was conducted by using the principles of meta-analysis on the statistical software RevMan version 5. Results: The search of medical databases yielded 13 studies (one randomised trial and 12 comparative studies) on 16,082 patients undergoing oncological and non-oncological colorectal resections. Eleven studies reported total cost whereas seven studies reported only operative cost. In the random effects model analysis, LCR was associated with the reduced total cost [standardised mean difference -62.34, 95% confidence interval (CI): -75.14 to -49.54, Z=9.55, P<0.001] as well as reduced operative cost (standardised mean difference -4.60, 95% CI: -5.90 to -3.31, Z=6.96, P<0.001) compared to RCR. However, there was significant heterogeneity [Tau2=346.74, Chi2=29,559.11, df =11 (P<0.001; I2=100%); Tau2=2.73, Chi2=832.21, df =6 (P<0.001; I2=99%)] among included studies. Conclusions: The LCR seems to be more economical as compared to the RCR in terms of operative cost as well as total cost (operative plus in-patient stay). However, due to statistically significant heterogeneity among included studies and paucity of the randomised trials, these findings should be taken cautiously.

16.
Int J Biometeorol ; 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38814475

RESUMEN

The current study attempts to investigate the differences in gene expression in longissimus thoracis muscles between sheep breeds acclimated to diverse environments. Changthangi sheep inhabits the cold arid plateau of Ladakh, at an altitude above 3000 m with prevalence of rarefied atmosphere. Muzzafarnagri sheep, on the other hand is found in the sub-tropical hot and humid plains at an altitude of about 250 m. Comparative transcriptomics was used to provide a molecular perspective of the differential adaptation of the two breeds. RNA sequencing data was generated from four biological replicates of the longissimus thoracis muscles from both breeds. The common genes expressed in both breeds were involved in muscle contraction and muscle fibre organization. The most significant pathways enriched in Changthangi muscles were glycogen metabolism, reduction of cytosolic Ca++ levels and NFE2L2 regulating anti-oxidant, while those in Muzzafarnagri were extracellular matrix organization and collagen formation. The hub genes identified in Changthangi were involved in hematopoiesis and HIF signaling pathway, suggesting the molecular acclimatization of Changthangi to the high altitude cold desert of Ladakh. The nodal genes discovered in Muzzafarnagri sheep were associated with the extracellular matrix which accentuates its significance in the development, growth and repair of muscles. The observed transcriptomic differences underscore the morphological and adaptive disparity between the two breeds. The candidate genes and pathways identified in this study will form the basis for future research on adaptation to high altitude and body size in small ruminants.

17.
IUBMB Life ; 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38733508

RESUMEN

The cholesterogenic phenotype, encompassing de novo biosynthesis and accumulation of cholesterol, aids cancer cell proliferation and survival. Previously, the role of cholesteryl ester (CE) transfer protein (CETP) has been implicated in breast cancer aggressiveness, but the molecular basis of this observation is not clearly understood, which this study aims to elucidate. CETP knock-down resulted in a >50% decrease in cell proliferation in both 'estrogen receptor-positive' (ER+; Michigan Cancer Foundation-7 (MCF7) breast cancer cells) and 'triple-negative' breast cancer (TNBC; MDA-MB-231) cell lines. Intriguingly, the abrogation of CETP together with the combination treatment of tamoxifen (5 µM) and acetyl plumbagin (a cholesterol-depleting agent) (5 µM) resulted in twofold to threefold increase in apoptosis in both cell lines. CETP knockdown also showed decreased intracellular CE levels, lipid raft and lipid droplets in both cell lines. In addition, RT2 Profiler PCR array (Qiagen, Germany)-based gene expression analysis revealed an overall downregulation of genes associated in cholesterol biosynthesis, lipid signalling and drug resistance in MCF7 cells post-CETP knock-down. On the contrary, resistance in MDA-MB-231 cells was reduced through increased expression in cholesterol efflux genes and the expression of targetable surface receptors by endocrine therapy. The pilot xenograft mice study substantiated CETP's role as a cancer survival gene as knock-down of CETP stunted the growth of TNBC tumour by 86%. The principal findings of this study potentiate CETP as a driver in breast cancer growth and aggressiveness and thus targeting CETP could limit drug resistance via the reduction in cholesterol accumulation in breast cancer cells, thereby reducing cancer aggressiveness.

18.
Sports Health ; : 19417381241249413, 2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38736252

RESUMEN

BACKGROUND: The recovery and rehabilitation journey after anterior cruciate ligament reconstruction (ACLR) surgery can be different for competitive and recreational athletes as their motivation and goals toward sports are different. HYPOTHESIS: Competitive athletes would present with better patient-reported outcomes and higher muscle strength compared with recreational athletes postsurgery. Second, competitive athletes would recover better (patient-reported outcome [PRO] measures and muscle strength) compared with recreational athletes at later stages. STUDY DESIGN: Cross-sectional laboratory-based study. LEVEL OF EVIDENCE: Level 2. METHODS: A total of 245 patients with unilateral ACLR were categorized as competitive or recreational athletes and grouped into early (4-6.9 months) or late (7-10 months) stages of recovery. PRO were collected for psychological response (Tampa Scale Kinesiophobia; Anterior Cruciate Ligament-Return to Sport after Injury), perceived knee function (International Knee Documentation Committee subjective form [IKDC]), and quality of life (Knee injury and Osteoarthritis Outcome Score; Veteran Rand-12). Isokinetic, concentric knee extension strength was measured bilaterally with a multimodal dynamometer (System 4, Biodex Medical Systems) at a speed of 90° and 180°/s. RESULTS: Competitive athletes had significantly higher scores for IKDC (P = 0.03), and quadriceps peak torque at 90°/s (P = 0.01) and 180°/s (P < 0.01) compared with recreational athletes. Competitive athletes had higher quadriceps strength at 90°/s (P < 0.01) and 180°/s (P = 0.02) in the late group. Recreational athletes displayed higher sports participation in the late group. CONCLUSION: Outcomes of ACLR may differ based on preinjury athletic level. Whereas competitive athletes had higher knee and muscle function than recreational athletes, psychological measures were not different among groups. CLINICAL RELEVANCE: There is a need for more individualized care for patients with ACLR since there is variability among patient goals postsurgery. This information might help set realistic expectations for competitive and recreational athletes after surgery.

19.
Mycoses ; 67(5): e13746, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38767275

RESUMEN

BACKGROUND: Post-tuberculosis lung abnormality (PTLA) is the most common risk factor for chronic pulmonary aspergillosis (CPA), and 14%-25% of the subjects with PTLA develop CPA. The pathogenesis and the host immune response in subjects with PTLA who develop CPA need to be better understood. METHODS: We prospectively compared the innate and adaptive immune responses mounted by patients of PTLA with or without CPA (controls). We studied the neutrophil oxidative burst (by dihydrorhodamine 123 test), classic (serum C3 and C4 levels) and alternative (mannose-binding lectin [MBL] protein levels) complement pathway, serum immunoglobulins (IgG, IgM and IgA), B and T lymphocytes and their subsets in subjects with PTLA with or without CPA. RESULTS: We included 111 subjects (58 CPA and 53 controls) in the current study. The mean ± SD age of the study population was 42.6 ± 15.7 years. The cases and controls were matched for age, gender distribution and body weight. Subjects with CPA had impaired neutrophil oxidative burst, lower memory T lymphocytes and impaired Th-1 immune response (lower Th-1 lymphocytes) than controls. We found no significant difference between the two groups in the serum complement levels, MBL levels, B-cell subsets and other T lymphocyte subsets. CONCLUSION: Subjects with CPA secondary to PTLA have impaired neutrophil oxidative burst and a lower Th-1 response than controls.


Asunto(s)
Inmunidad Adaptativa , Inmunidad Innata , Aspergilosis Pulmonar , Tuberculosis Pulmonar , Humanos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Tuberculosis Pulmonar/inmunología , Tuberculosis Pulmonar/complicaciones , Estudios Prospectivos , Aspergilosis Pulmonar/inmunología , Aspergilosis Pulmonar/complicaciones , Neutrófilos/inmunología , Pulmón/inmunología , Estallido Respiratorio , Adulto Joven
20.
Artículo en Inglés | MEDLINE | ID: mdl-38639270

RESUMEN

It was in 2019 that the world experienced the devastation caused by SARS-COV-2, contributing to a large number of deaths. This contagious virus not only challenged the health care system but has also hit the economy very badly. There has been a lot of research on effective vaccine development, and there has been some success in the same, but no effective antiviral drugs are available in the market. No doubt vaccination can prevent the disease, but it doesn't have the potential to cure an infected person, for which there is a dire need to develop some effective drug. Angiotensin convertase enzyme 2 (ACE2) played a substantial role in SARS-COV2 pathogenesis and thus has gained much attention during the pandemic. Moreover, it has opened up new avenues for the cure of COVID-19.

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