Functional transcriptome analysis revealed major changes in pathways affecting systems biology of Tharparkar cattle under seasonal heat stress.

Heat stress significantly disturbs the production, reproduction, and systems biology of dairy cattle. A complex interaction among biological systems helps to combat and overcome heat stress. Indicine cattle breed Tharparkar has been well known for its thermal adaptability. Therefore, present investigation considered RNA-seq technology to explore the functional transcriptomics of Tharparkar cattle with the help of samples collected in spring and summer season. Among differentially expressed genes, about 3280 genes were highly dysregulated, in which 1207 gene were upregulated and 2073 genes were downregulated (|log2fold change|≥ 1 and p ≤ 0.05). Upregulated genes were related to insulin activation, interferons, and potassium ion transport. In contrast, downregulated genes were related to RNA processing, translation, and ubiquitination. Functional annotation revealed that the pathways associated with nervous system (NPFFR1, ROBO3) and metal ion transport (KCNG2, ATP1A2) were highly activated while mRNA processing and translation (EIF4A, EIF4B) and protein processing pathway (VPS4B, PEX13) were highly downregulated. Protein-protein interactions identified hub genes such as ATP13A3, IFNGR2, UBXN7, EIF4A2, SLC12A8 found to play an important role in immune, ubiquitination, translation and transport function. Co-expression network includes LYZ, PNRC1, SQSTM1, EIF4AB and DDX17 genes which are involved in lysosomal activity, tumor inhibition, ubiquitination, and translation initiation. Chemokine signaling pathway associated with immune response was highly upregulated in cluster analysis. The findings of this study provide insights into transcriptome expression and regulation which may better explain complex thermal resilience mechanism of Tharparkar cattle in heat stress under natural conditions. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04018-2.

Incidental Apical Pleuroparenchymal Scarring on Computed Tomography: Diagnostic Yield, Progression, Morphologic Features and Clinical Significance.

PURPOSE: Apical pleuroparenchymal scarring (APPS) is commonly seen on chest computed tomography (CT), though the imaging and clinical features, to the best of our knowledge, have never been studied. The purpose was to understand APPS's typical morphologic appearance and associated clinical features. PATIENTS AND METHODS: A random generator selected 1000 adult patients from all 21516 chest CTs performed at urban outpatient centers from January 1, 2016 to December 31, 2016. Patients with obscuring apical diseases were excluded to eliminate confounding factors. After exclusions, 780 patients (median age: 64 y; interquartile range: 56 to 72 y; 55% males) were included for analysis. Two radiologists evaluated the lung apices of each CT for the extent of abnormality in the axial plane (mild: <5 mm, moderate: 5 to 10 mm, severe: >10 mm), craniocaudal plane (extension halfway to the aortic arch, more than halfway, vs below the arch), the predominant pattern (nodular vs reticular and symmetry), and progression. Cohen kappa coefficient was used to assess radiologists' agreement in scoring. Ordinal logistic regression was used to determine associations of clinical and imaging variables with APPS. RESULTS: APPS was present on 65% (507/780) of chest CTs (54% mild axial; 80% mild craniocaudal). The predominant pattern was nodular and symmetric. Greater age, female sex, lower body mass index, greater height, and white race were associated with more extensive APPS. APPS was not found to be associated with lung cancer in this cohort. CONCLUSION: Classifying APPS by the extent of disease in the axial or craniocaudal planes, in addition to the predominant pattern, enabled statistically significant associations to be determined, which may aid in understanding the pathophysiology of apical scarring and potential associated risks.

Breast cancer and its therapeutic targets: A comprehensive review.

Breast cancer is a common and deadly disease, so there is a constant need for research to find efficient targets and therapeutic approaches. Breast cancer can be classified on a molecular and histological base. Breast cancer can be divided into ER (estrogen receptor)-positive and ER-negative, HER2 (human epidermal growth factor receptor2)-positive and HER2-negative subtypes based on the presence of specific biomarkers. Targeting hormone receptors, such as the HER2, progesterone receptor (PR), and ER, is very significant and plays a vital role in the onset and progression of breast cancer. Endocrine treatments and HER2-targeted drugs are examples of targeted therapies now being used against these receptors. Emerging immune-based medicines with promising outcomes in the treatment of breast cancer include immune checkpoint inhibitors, cancer vaccines, and adoptive T-cell therapy. It is also explored how immune cells and the tumor microenvironment affect breast cancer development and treatment response. The major biochemical pathways, signaling cascades, and DNA repair mechanisms that are involved in the development and progression of breast cancer, include the PI3K/AKT/mTOR system, the MAPK pathway, and others. These pathways are intended to be inhibited by a variety of targeted drugs, which are then delivered with the goal of restoring normal cellular function. This review aims to shed light on types of breast cancer with the summarization of different therapeutic approaches which can target different pathways for tailored medicines and better patient outcomes.

Integrated bioinformatics approaches to investigate alterations in transcriptomic profiles of monkeypox infected human cell line model.

BACKGROUND: The recent re-emergence of the monkeypox (mpox) epidemic in nonendemic regions has raised concerns regarding a potential global outbreak. The mpox virus (MPV) is a smallpox-like virus belonging to the genus Orthopoxvirus (family: Poxviridae). Although studies suggest that MPV infection suppresses the Toll-like receptor-3- and tumor necrosis factor-α-related signaling pathways, whether MPV regulates other immune-related pathways remains unclear. METHODS: In this study, two distinct temporal patterns were used for establishing an MPV-infected human immortal epithelial cancer cell line (HeLa). These two durations 2 and 12 h of incubation were selected to identify the coregulated genes and pathways affected by MPV infection. RESULTS: The use of the Gene Ontology framework, Kyoto Encyclopedia of Genes and Genome database, and MetaCore software yielded valuable insights. Specifically, various pathways were found to be enriched in HeLa cells infected with MPV for 2 and 12 h. These pathways included Notch, CD40, CD95, hypoxia-inducible factor-1-α, interleukin (IL)- 1, IL-6, phosphoinositide 3-kinase, nuclear factor-κB, mitogen-activated protein kinase, and oxidative stress-induced signalling pathways. Clusters and pathways of metabolism and viral replication cycles were significantly associated with the 2-hour infection group. This association was identified based on the regulation of genes such as HSPG2, RHPN2, MYL1, ASPHD2, CA9, VIPR1, SNX12, MGC2752, SLC25A1, PEX19, and AREG. Furthermore, clusters and pathways related to immunity and cell movement were found to be associated with the 12-hour infection group. This association was identified based on the regulation of genes such as C1orf21, C19orf48, HRK, IL8, GULP1, SCAND2, ATP5C1, FEZ1, SGSH, TACC2, CYP4X1, MMP1, CPB1, P2RY13, WDR27, PRPF4, and ENDOD1. CONCLUSIONS: This study can improve our understanding of the mechanisms underlying the pathophysiology and post-infection sequelae of mpox. Our findings provide valuable insights into the various modes of MPV infection.

Does early exposure to cardiothoracic surgery increase interest in the specialty?

INTRODUCTION: The number of applications for cardiothoracic surgery has been steadily dropping over the past decades. We aim to assess whether a 1-day cardiothoracic surgical skills conference could increase interest into the speciality. METHODS: Participants included in the study had to be medical students or junior doctors. Out of 57 delegates that attended the conference, 52 were enrolled in the study, and completed the pre-conference and post-conference questionnaires. Three introductory lectures were delivered by consultants in cardiothoracic surgery or cardiology in the morning, followed by three practical surgical workshops. We assessed demographics, confidence in and knowledge of procedures, and the change in participants' interest in the speciality pre- and post-conference. This study was conducted at St George's University of London. RESULTS: The interest to pursue a career in cardiothoracic surgery increased by 23% post-conference (p = .035). Confidence and knowledge in all procedures taught improved significantly after the conference (p < .05), with the highest increase seen in anastomosis of vessels (p < .0001). Preclinical students made up 57.7% of participants, majority of whom had not seen more than three surgical procedures. CONCLUSION: Our conference has shown to increase interest in cardiothoracic surgery and improve exposure to surgical skills, especially to those in early years of medical school. The surgical workshops improved student confidence and knowledge in procedures used within the field and the use of animal tissue improved participant experience. Further research is needed at other medical schools to assess whether a change in surgical skills teaching should be made to medical school curriculums.

Sex-specific prevalence, awareness, treatment and control of hypertension in adults in India: a study for developing sex-specific public policy from the longitudinal ageing study in India (LASI) data 2017-2018.

BACKGROUND AND OBJECTIVE: Hypertension is a key risk factor for cardiovascular disease and the leading cause of mortality among Indian adults. The difference in health status between men and women is becoming a great burden in itself worldwide. This study aimed to examine the differences between men and women in the prevalence, awareness, treatment, and control of hypertension and related risk factors among people aged 45 and older in India using data from the Longitudinal Ageing Study in India in 2017-2018. METHODS: Descriptive statistics were presented separately for males and females. Multivariable logistic regression was used to analyze the socio-demographic, lifestyle behaviours, and biological factors associated with the prevalence of hypertension. All statistical analyses were conducted using Stata Version 16.0 statistical software. The study of the data was conducted using survey weights available in the LASI datasets. KEY FINDINGS: Overall, the study found that 45.1% of the study population had hypertension, with 26.9% self-reporting their condition and 30% having hypertension at the time of measurement. Approximately 41% of males and 59% of females had hypertension. The self-reported hypertension of men was found to differ significantly from measured hypertension by 8.7%, while in women the difference was only 1.2%. Diabetes was found to increase the odds of having hypertension in both males (OR = 3.65, 95% CI (3.37-3.97)) and females (OR = 3.46, 95% CI (3.21-3.74)). CONCLUSION: The difference between self-reported and measured hypertension in men and women is contributing to sex-gender and health inequalities that must be addressed. For adult females with hypertension, it is important to prioritize obesity, education level, physical activity, and regular clinic visits to manage chronic conditions. Based on our findings, policy recommendations can be made to focus on increasing women's literacy, promoting men's screening for hypertension, banning tobacco and alcohol sales, and organizing hypertension awareness campaigns specifically for men and in rural areas.

Development of reliable quantitative structure-toxicity relationship models for toxicity prediction of benzene derivatives using semiempirical descriptors.

The Health and environmental hazards of benzene and nitrobenzene (NB) derivatives have remained a topic of interest of researchers. In silico methods for prediction of toxicity of chemicals have proved their worth in accurate forecast of environmental as well as health toxicity and are strongly recommended by regulatory authorities. Two quantitative structure-toxicity relationship (QSTR) models explaining Scenedesmus obliquus toxicity trends among 39 benzene derivatives and Tetrahymena pyriformis toxicity of 103 NB and 392 benzene derivatives are developed using semiempirical quantum chemical parameters. The best constructed QSTR models have good fitting ability (R2 = 0.8053, 0.7591, and 0.8283) and robustness (Q2LOO = 0.7507, 0.7227, and 0.8194; Q2LMO = 0.7338, 0.7153, and 0.8172). The external predictivity of all the models are quite good (R2EXT = 0.8256, 0.9349, and 0.8698). Electronegativity, Cosmo volume, total energy, and molecular weight are responsible for the increase and decrease of toxicity of benzene derivatives against S. obliquus while electronegativity, electrophilicity index, the heat of formation, total energy, hydrophobicity, and cosmo volume are responsible for modulation of toxicity of NB and benzene derivatives toward T. pyriformis. These models fulfill the requirements of all the five OECD principles.

An Insight into Diverse Activities and Targets of Flavonoids.

BACKGROUND: Flavonoids belong to the chemical class of polyphenols and are in the category of secondary metabolites imparting a wide protective effect against acute and chronic diseases. OBJECTIVE: The study aims to investigate and summarize the information of various flavonoids extracted, isolated from various sources, and possess different pharmacological properties by acting on multiple targets. METHODS: This comprehensive review summarizes the research information related to flavonoids and their pharmacological action targets from various sources like PubMed, Google Scholar and Google websites. RESULTS: Extracted information in the paper discusses various therapeutic effects of flavonoids isolated from medicinal plant sources, which have the property to inhibit several enzymes, which finally results in health benefits like anti-cancer, anti-bacterial, antioxidant, anti-allergic, and anti-viral effects. This study also showed the different solvents and methods involved in the extraction and characterization of the isolated phytochemical constituents. CONCLUSION: The findings showed the contribution of several flavonoids in the management and inhibition of various acute and chronic sicknesses by acting on different sites in the body. This study may lead to gaining interest for more research on the bioactives of different medicinal plants for the discovery of new lead compounds or further improvement of the efficacy of the existing compound.

YAP/TAZ Mediate TGFß2-Induced Schlemm's Canal Cell Dysfunction.

Purpose: Elevated transforming growth factor beta2 (TGFß2) levels in the aqueous humor have been linked to glaucomatous outflow tissue dysfunction. Potential mediators of dysfunction are the transcriptional coactivators, Yes-associated protein (YAP) and transcriptional coactivator with PDZ binding motif (TAZ). However, the molecular underpinnings of YAP/TAZ modulation in Schlemm's canal (SC) cells under glaucomatous conditions are not well understood. Here, we investigate how TGFß2 regulates YAP/TAZ activity in human SC (HSC) cells using biomimetic extracellular matrix hydrogels, and examine whether pharmacological YAP/TAZ inhibition would attenuate TGFß2-induced HSC cell dysfunction. Methods: Primary HSC cells were seeded atop photo-cross-linked extracellular matrix hydrogels, made of collagen type I, elastin-like polypeptide and hyaluronic acid, or encapsulated within the hydrogels. HSC cells were induced with TGFß2 in the absence or presence of concurrent actin destabilization or pharmacological YAP/TAZ inhibition. Changes in actin cytoskeletal organization, YAP/TAZ activity, extracellular matrix production, phospho-myosin light chain levels, and hydrogel contraction were assessed. Results: TGFß2 significantly increased YAP/TAZ nuclear localization in HSC cells, which was prevented by either filamentous-actin relaxation or depolymerization. Pharmacological YAP/TAZ inhibition using verteporfin without light stimulation decreased fibronectin expression and actomyosin cytoskeletal rearrangement in HSC cells induced by TGFß2. Similarly, verteporfin significantly attenuated TGFß2-induced HSC cell-encapsulated hydrogel contraction. Conclusions: Our data provide evidence for a pathologic role of aberrant YAP/TAZ signaling in HSC cells under simulated glaucomatous conditions and suggest that pharmacological YAP/TAZ inhibition has promising potential to improve outflow tissue dysfunction.

New or enlarging hiatal hernias after thoracic surgery for early lung cancer.

Objective: The study objective was to determine the relationship between lung resection and the development of postoperative hiatal hernia. Methods: Preoperative and postoperative computed tomography imaging from 373 patients from the International Early Lung Cancer Action Program and the Initiative for Early Lung Cancer Research on Treatment were compared at a median of 31.1 months of follow-up after resection of clinical early-stage non-small cell lung cancer. Incidence of new hiatal hernia or changes to preexisting hernias were recorded and evaluated by patient demographics, surgical approach, extent of resection, and resection site. Results: New hiatal hernias were seen in 9.6% of patients after lung resection (5.6% after wedge or segmentectomy and 12.4% after lobectomy; P = .047). The median size of new hernias was 21 mm, and the most commonly associated resection site was the left lower lobe (24.2%; P = .04). In patients with preexisting hernias, 53.5% demonstrated a small but significant increase in size from 21 to 22 mm (P < .0001). All hernias persisted through the latest postoperative computed tomography scan. When 110 surgical patients without preexisting hernia were matched by sex, age, and smoking to nonoperative controls, the incidence of new hernia at follow-up was significantly higher among those who underwent surgery (17.3% vs 2.7%, P = .0003). Conclusions: Both open and minimally invasive lung resection for clinical early-stage lung cancer are associated with new or enlarging postoperative hiatal hernia, especially after resections involving the left lower lobe.

Engineering a 3D hydrogel system to study optic nerve head astrocyte morphology and behavior.

In glaucoma, astrocytes within the optic nerve head (ONH) rearrange their actin cytoskeleton, while becoming reactive and upregulating intermediate filament glial fibrillary acidic protein (GFAP). Increased transforming growth factor beta 2 (TGF ß2) levels have been implicated in glaucomatous ONH dysfunction. A key limitation of using conventional 2D culture to study ONH astrocyte behavior is the inability to faithfully replicate the in vivo ONH microenvironment. Here, we engineer a 3D ONH astrocyte hydrogel to better mimic in vivo mouse ONH astrocyte (MONHA) morphology, and test induction of MONHA reactivity using TGF ß2. Primary MONHAs were isolated from C57BL/6J mice and cell purity confirmed. To engineer 3D cell-laden hydrogels, MONHAs were mixed with photoactive extracellular matrix components (collagen type I, hyaluronic acid) and crosslinked for 5 minutes using a photoinitiator (0.025% riboflavin) and UV light (405-500 nm, 10.3 mW/cm2). MONHA-encapsulated hydrogels were cultured for 3 weeks, and then treated with TGF ß2 (2.5, 5.0 or 10 ng/ml) for 7 days to assess for reactivity. Following encapsulation, MONHAs retained high cell viability in hydrogels and continued to proliferate over 4 weeks as determined by live/dead staining and MTS assays. Sholl analysis demonstrated that MONHAs within hydrogels developed increasing process complexity with increasing process length over time. Cell processes connected with neighboring cells, coinciding with Connexin43 expression within astrocytic processes. Treatment with TGF ß2 induced reactivity in MONHA-encapsulated hydrogels as determined by altered F-actin cytoskeletal morphology, increased GFAP expression, and elevated fibronectin and collagen IV deposition. Our data sets the stage for future use of this 3D biomimetic ONH astrocyte-encapsulated hydrogel to investigate astrocyte behavior in response to injury.

Progression of probable UIP and UIP on HRCT.

PURPOSE: To determine patterns of progression of probable Usual Interstitial Pneumonitis (UIP). METHODS: This HIPPA compliant, IRB-approved study draws patients from our Fibrosis Registry. All patients with a consensus diagnosis of Idiopathic Pulmonary Fibrosis (IPF) were included. Most recent CT scans and all earlier CT scans were reviewed to determine the fibrosis grade in each lobe based on probable UIP (pUIP) findings of ground glass opacities, traction bronchiolectasis and reticulations or UIP findings of subpleural basilar predominant fibrosis with honeycombing (HC) and absence of features that would suggest an alternative diagnosis. RESULTS: 103 patients with a working diagnosis of IPF are the focus of this report. Among the 68 with pUIP on the initial CT, 32 (47%) progressed; median time to progression was 51 months. The risk of HC progression, adjusted for gender, of patients with emphysema was 2.53 times higher than patients without emphysema (HR = 2.53, 95% CI: 1.06-6.02). Among the 35 with HC on the initial CT scan, 20 (57%) progressed to more advanced HC; median time to progression was 31 months. Increased pulmonary artery size was significantly associated with an elevated risk for more advanced HC progression (HR = 1.16, 95% CI: 1.04-1.31). CONCLUSION: Ground glass opacities, traction bronchiolectasis and reticulations, a "Probable UIP Pattern" by ATS criteria progressed to UIP in 47% of patients on follow-up imaging.

The need to be all inclusive: Chest CT scans should include imaged breast parenchyma.

The benefits of early diagnosis and treatment of breast cancer are well established. Thoracic CT which is performed with increased frequency for lung cancer screening can diagnose breast cancer earlier then might be possible clinically. The imaged and radiation exposed breasts must be included in their entirety on images which are reviewed by the radiologist. Because of concerns about how altering the field of view might affect image quality, we advocate for inclusion of the entire breast on the soft tissue series, which can be viewed on mediastinal window settings and expose the patient to no additional radiation.

Nonamyloid tumoral light-chain-deposition disease (aggregoma) of the paraspinal region.

Aggregomas are rare localized masses of monoclonal nonamyloid immunoglobulin light-chain deposits. To date, there have been only a few reports of isolated aggregomas, with the majority detailing renal, lymph node and brain deposition. We present a rare case of paraspinal aggregoma in a 67-year-old female who presented with a complaint of cough and chest pain. Imaging demonstrated a left-sided paravertebral mass extending from T7-T10. Pathological analysis showed lamellar deposition of extracellular eosinophilic material with an associated lymphoplasmacytic nonamyloid infiltrate. To our knowledge, this is the first report of a paraspinal aggregoma. While exceedingly rare, this tumor can be included in the radiologic differential diagnosis of paravertebral soft tissue tumors in adults. The observation of our case adds to the limited understanding of the etiology, pathogenesis, natural history, and treatment of nonamyloid light-chain depositions.

Novel approach for the percutaneous treatment of left ventricular pseudoaneurysms.

Left ventricular pseudoaneurysm (LVPA) is a rare yet serious complication that may follow cardiac surgery, myocardial infarction, trauma, or infection. If left untreated, reported rates of rupture and sudden cardiac death are high. Although surgical intervention has traditionally been the standard treatment for LVPA, percutaneous closure is now an attractive alternative in the high-risk patient. We report a case of a successful percutaneous LVPA closure using direct chest wall entry into the pseudoaneurysm. This novel approach can be useful when access to the LVPA is a challenge, especially in the setting of small ostial size, dense left ventricular trabeculations, angulated serpiginous tract, and presence of mechanical prostheses.