Promising Combinatorial Therapeutic Strategies against Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) presents a complex and diverse disease, exhibiting variations at individuals' cellular and histological levels. This complexity gives rise to different subtypes and genetic mutations, posing challenges for accurate diagnosis and effective treatment. Nevertheless, continuous progress in medical research and therapies is continually shaping the landscape of NSCLC diagnosis and management. The treatment of NSCLC has undergone significant advancements in recent years, especially with the emergence of targeted therapies that have shown remarkable efficacy in patients with actionable mutations. This has ushered in the era of personalized medicine in NSCLC treatment, with improvements in molecular and immunohistochemical techniques contributing to enhanced progression-free survival. This review focuses on the latest progress, challenges, and future directions in developing targeted therapies for NSCLC, including tyrosine kinase inhibitors (TKIs), DNA-damaging agents, immunotherapy regimens, natural drug therapy, and nanobodies. Furthermore, recent randomized studies have demonstrated enhanced overall survival in patients receiving different targeted and natural drug therapies.

Social and Biological Determinants in Lung Cancer Disparity.

Lung cancer remains a leading cause of death in the United States and globally, despite progress in treatment and screening efforts. While mortality rates have decreased in recent years, long-term survival of patients with lung cancer continues to be a challenge. Notably, African American (AA) men experience significant disparities in lung cancer compared to European Americans (EA) in terms of incidence, treatment, and survival. Previous studies have explored factors such as smoking patterns and complex social determinants, including socioeconomic status, personal beliefs, and systemic racism, indicating their role in these disparities. In addition to social factors, emerging evidence points to variations in tumor biology, immunity, and comorbid conditions contributing to racial disparities in this disease. This review emphasizes differences in smoking patterns, screening, and early detection and the intricate interplay of social, biological, and environmental conditions that make African Americans more susceptible to developing lung cancer and experiencing poorer outcomes.

Physicochemical assessment of industrial effluents of Kala Sanghian drain, Punjab, India.

The discharge of industrial effluents has a significant impact on the Water Quality Index (WQI) of the water bodies and is a major source of contamination of groundwater. The present study investigated the physicochemical characteristics and scrutinized the pollution potential of the tannery, textile, and electroplating effluents uploading into the Kala Sanghian drain, located in Jalandhar, Punjab, India. In this study, 12 samples were collected from the four sites (leather complex drain (LD), leather complex outlet (LO), focal point drain (FD), and Bulandpur drain (BD)) of Kala Sanghian drain in the dry season. The result showed that the drain under consideration is very much contaminated and the water is not suitable for irrigation and agricultural purposes. Rather it has a bad impact on the health of local people, the physiology of aquatic organisms, and the soil quality of agricultural land nearby. The present study confirmed the water quality index was more than 100, indicating a highly contaminated drain and water is unfit for any use. The correlation analysis shows that there exists a positive correlation between TDS and temperature (r = 0.994), DO and pH (r = 0.808), BOD and temperature (r = 0.987), BOD and TDS (r = 0.978), EC and temperature (r = 0.963), EC and TDS (r = 0.954), and EC and BOD (r = 0.956). The principal component analysis (PCA) confirms that PC1 alone has more than 89% of the variance with high positive loading for TDS, temperature, EC, and BOD. The hierarchical cluster analysis (HCA) reflected two clusters where cluster 1 consists of pH, DO, temperature, and BOD of water while cluster 2 consists of TDS and EC of water. The PCA and HCA study of the data set confirms the high degree contribution of anthropogenic activities through the application of chemicals in agriculture, disposal of municipal waste, and industrial effluents in the deterioration of water quality. The results of the study will help to enhance the sustainable action plan for the management of industrial effluents in the studied area.

Volatile organic compounds: A threat to the environment and health hazards to living organisms - A review.

Volatile organic compounds (VOCs) are the organic compounds having a minimum vapor pressure of 0.13 kPa at standard temperature and pressure (293 K, 101 kPa). Being used as a solvent for organic and inorganic compounds, they have a wide range of applications. Most of the VOCs are non-biodegradable and very easily become component of the environment and deplete its purity. It also deteriorates the water quality index of the water bodies, impairs the physiology of living beings, enters the food chain by bio-magnification and degrades, decomposes and manipulates the physiology of living organisms. To unveil the adverse impacts of volatile organic compounds (VOCs) and their rapid eruption and interference in the living world, a review has been designed. This review presents an insight into the currently available VOCs, their sources, applications, sampling methods, analytic procedures, imposition on the health of aquatic and terrestrial communities and their contamination of the environment. Elaboration has been done on representation of toxicological effects of VOCs on vertebrates, invertebrates, and birds. Subsequently, the role of environmental agencies in the protection of environment has also been illustrated.

Effect of platelet counts and activator in platelet-rich plasma on the treatment of androgenetic alopecia, split-head comparison: A randomised, double-blind study.

Background Androgenetic alopecia is a common, chronic, non-scarring alopecia. It is characterised by stepwise miniaturisation of the hair follicles, due to alteration in the hair cycle dynamics, leading to the transformation of terminal hair follicles into a vellus ones. Oral finasteride and topical minoxidil are the only approved drugs for treating this condition. Due to a limited number of effective therapies for androgenetic alopecia, platelet-rich plasma may be an effective alternative treatment. Aims To study the effect of activator in platelet-rich plasma and baseline platelet count in platelet-rich plasma on the treatment of androgenetic alopecia. Methods A randomised, double-blind split-head comparative study. The sample size was calculated and randomisation was done. Patients with androgenetic alopecia were allocated into two groups; in the first group, autologous activated platelet-rich plasma was injected in the right half of the affected scalp and autologous non-activated platelet-rich plasma was injected in the left half of the affected scalp and vice versa in the second group. Patients were also categorised on the basis of platelet counts in their platelet-rich plasma in three groups; group A (6-8 lakh/mm3), group B (8.1-10 lakh/mm3) and group C (>10 lakh/mm3). Interventions were done monthly for three months and followed up for the next three months. Effects of interventions were assessed by hair density, hair thickness, patient self-assessment and clinical photography. Results A total of 80 patients were included in the study. Activated platelet-rich plasma produced significant improvement of hair density after four months and hair thickness at 6 months. An increase in platelet count led to a significant increase in hair density and hair thickness after three and four months respectively and a highly significant increase in both parameters at the end of the study. Limitations Long-term follow-up of cases was not done and no measurement of vellus hair count was done. Conclusion There is a significant effect of activator and platelet count of the platelet-rich plasma on hair density as well as hair thickness.

Smart and Adaptive Architecture for a Dedicated Internet of Things Network Comprised of Diverse Entities: A Proposal and Evaluation.

Advances in 5G and the Internet of Things (IoT) have to cater to the diverse and varying needs of different stakeholders, devices, sensors, applications, networks, and access technologies that come together for a dedicated IoT network for a synergistic purpose. Therefore, there is a need for a solution that can assimilate the various requirements and policies to dynamically and intelligently orchestrate them in the dedicated IoT network. Thus we identify and describe a representative industry-relevant use case for such a smart and adaptive environment through interviews with experts from a leading telecommunication vendor. We further propose and evaluate candidate architectures to achieve dynamic and intelligent orchestration in such a smart environment using a systematic approach for architecture design and by engaging six senior domain and IoT experts. The candidate architecture with an adaptive and intelligent element ("Smart AAA agent") was found superior for modifiability, scalability, and performance in the assessments. This architecture also explores the enhanced role of authentication, authorization, and accounting (AAA) and makes the base for complete orchestration. The results indicate that the proposed architecture can meet the requirements for a dedicated IoT network, which may be used in further research or as a reference for industry solutions.

Genome-wide association mapping identifies an SNF4 ortholog that impacts biomass and sugar yield in sorghum and sugarcane.

Sorghum is a feed/industrial crop in developed countries and a staple food elsewhere in the world. This study evaluated the sorghum mini core collection for days to 50% flowering (DF), biomass, plant height (PH), soluble solid content (SSC), and juice weight (JW), and the sorghum reference set for DF and PH, in 7-12 testing environments. We also performed genome-wide association mapping with 6 094 317 and 265 500 single nucleotide polymorphism markers in the mini core collection and the reference set, respectively. In the mini core panel we identified three quantitative trait loci for DF, two for JW, one for PH, and one for biomass. In the reference set panel we identified another quantitative trait locus for PH on chromosome 6 that was also associated with biomass, DF, JW, and SSC in the mini core panel. Transgenic studies of three genes selected from the locus revealed that Sobic.006G061100 (SbSNF4-2) increased biomass, SSC, JW, and PH when overexpressed in both sorghum and sugarcane, and delayed flowering in transgenic sorghum. SbSNF4-2 encodes a γ subunit of the evolutionarily conserved AMPK/SNF1/SnRK1 heterotrimeric complexes. SbSNF4-2 and its orthologs will be valuable in genetic enhancement of biomass and sugar yield in plants.

The interplay of pineal hormones and socioeconomic status leading to colorectal cancer disparity.

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. Despite increased screening options and state-of-art treatments offered in clinics, racial differences remain in CRC. African Americans (AAs) are disproportionately affected by the disease; the incidence and mortality are higher in AAs than Caucasian Americans (CAs). At the time of diagnosis, AAs more often present with advanced stages and aggressive CRCs, primarily accounting for the racial differences in therapeutic outcomes and mortality. The early incidence of CRC in AAs could be attributed to race-specific gene polymorphisms and lifestyle choices associated with socioeconomic status (SES). Altered melatonin-serotonin signaling, besides the established CRC risk factors (age, diet, obesity, alcoholism, and tobacco use), steered by SES, glucocorticoid, and Vitamin D status in AAs could also account for the early incidence in this racial group. This review focuses on how the lifestyle factors, diet, allelic variants, and altered expression of specific genes could lead to atypical serotonin and melatonin signaling by modulating the synthesis, secretion, and signaling of these pineal hormones in AAs and predisposing them to develop more aggressive CRC earlier than CAs. Crosstalk between gut microbiota and pineal hormones and its impact on CRC pathobiology is addressed from a race-specific perspective. Lastly, the status of melatonin-focused CRC treatments, the need to better understand the perturbed melatonin signaling, and the potential of pineal hormone-directed therapeutic interventions to reduce CRC-associated disparity are discussed.

Awareness, Use and Outlook of Complementary and Alternative Medicine (CAM) Options in an Underserved, Uninsured Minority Cancer Patient Population.

Integrative oncology aims to coordinate the delivery of conventional medicine and evidence-supported complementary and alternative medicine (CAM) to patients receiving cancer care. This field developed out of an increased interest in CAM usage among cancer patients. However, CAM use among medically underserved cancer patients remains to be well characterized. We evaluated CAM awareness as well as prevalence and characteristics of CAM use in 170 consecutive, medically underserved cancer patients presenting to a large, academic, inner-city cancer clinic, using a survey tool. Fifty-three participants declined participation and 17 survey results were incomplete. Therefore, 100 survey results were included in the final analysis. There were 65 males and 35 females in the survey with a mean age of 64.2 years. About 98% of the respondents were African American while 2% identified themselves as Hispanic. About 45% of patients had metastatic cancer, 24% had early-stage disease while 31% of patients were not aware of the stage of their cancer. About 55% patients had elementary school or lower level of education while only 16% had a college degree or higher. About 92% of respondents were unemployed. Some knowledge of CAM was reported by 22% of patients, while CAM use was reported in only 16% of patients. Female sex and college degree were significantly associated with CAM use. The most commonly used CAM modality was meditation (56%), followed by herbal remedies (31%), yoga (31%), and acupuncture (12%). Among CAM users, a majority used multiple CAM therapies. All users reported benefit from CAM use. Emotional wellbeing was the most common benefit followed by improvement in treatment related adverse effects, chemotherapy related symptoms, pain, and sleep. Even though the majority of our surveyed patients never used CAM, 90% of non-users were interested in gaining more information about the various CAM options and exploring its use and potential benefits. The majority (70%) wanted their primary oncologist to provide information about CAM options and discuss its safety and potential complementary benefit in management of their cancer and associated symptoms.

Genome-Wide Association Mapping Identifies Novel Panicle Morphology Loci and Candidate Genes in Sorghum.

Panicle morphology is an important trait in racial classification and can determine grain yield and other agronomic traits in sorghum. In this study, we performed association mapping of panicle length, panicle width, panicle compactness, and peduncle recurving in the sorghum mini core panel measured in multiple environments with 6,094,317 single nucleotide polymorphism (SNP) markers. We mapped one locus each on chromosomes 7 and 9 to recurving peduncles and eight loci for panicle length, panicle width, and panicle compactness. Because panicle length was positively correlated with panicle width, all loci for panicle length and width were colocalized. Among the eight loci, two each were on chromosomes 1, 2, and 6, and one each on chromosomes 8 and 10. The two loci on chromosome 2, i.e., Pm 2-1 and Pm 2-2, were detected in 7 and 5 out of 11 testing environments, respectively. Pm 2-2 colocalized with panicle compactness. Candidate genes were identified from both loci. The rice Erect Panicle2 (EP2) ortholog was among the candidate genes in Pm 2-2. EP2 regulates panicle erectness and panicle length in rice and encodes a novel plant-specific protein with unknown functions. The results of this study may facilitate the molecular identification of panicle morphology-related genes and the enhancement of yield and adaptation in sorghum.

Targeting novel coronavirus SARS-CoV-2 spike protein with phytoconstituents of Momordica charantia.

BACKGROUND: Infections by the SARS-CoV-2 virus causing COVID-19 are presently a global emergency. The current vaccination effort may reduce the infection rate, but strain variants are emerging under selection pressure. Thus, there is an urgent need to find drugs that treat COVID-19 and save human lives. Hence, in this study, we identified phytoconstituents of an edible vegetable, Bitter melon (Momordica charantia), that affect the SARS-CoV-2 spike protein. METHODS: Components of Momordica charantia were tested to identify the compounds that bind to the SARS-CoV-2 spike protein. An MTiOpenScreen web-server was used to perform docking studies. The Lipinski rule was utilized to evaluate potential interactions between the drug and other target molecules. PyMol and Schrodinger software were used to identify the hydrophilic and hydrophobic interactions. Surface plasmon resonance (SPR) was employed to assess the interaction between an extract component (erythrodiol) and the spike protein. RESULTS: Our in-silico evaluations showed that phytoconstituents of Momordica charantia have a low binding energy range, -5.82 to -5.97 kcal/mol. A docking study revealed two sets of phytoconstituents that bind at the S1 and S2 domains of SARS-CoV-2. SPR showed that erythrodiol has a strong binding affinity (KD = 1.15 µM) with the S2 spike protein of SARS-CoV-2. Overall, docking, ADME properties, and SPR displayed strong interactions between phytoconstituents and the active site of the SARS-CoV-2 spike protein. CONCLUSION: This study reveals that phytoconstituents from bitter melon are potential agents to treat SARS-CoV-2 viral infections due to their binding to spike proteins S1 and S2.

Atherosclerosis, Ischemia, and Anticancer Drugs.

The heart is affected by cardiotoxicity of anticancer drugs. Myocardium, pericardium and endocardium can be affected. Besides these coronary arteries can be affected by accelerated atherosclerosis. Various pathogenic mechanisms have been proposed that underlie the ischemic complications of anticancer drugs. In this review we discuss the atherosclerotic and ischemic complications of anticancer drugs.

CCL25 Signaling in the Tumor Microenvironment.

Multiple checkpoint mechanisms are overridden by cancer cells in order to develop into a tumor. Neoplastic cells, while constantly changing during the course of cancer progression, also craft their surroundings to meet their growing needs. This crafting involves changing cell surface receptors, affecting response to extracellular signals and secretion of signals that affect the nearby cells and extracellular matrix architecture. This chapter briefly comprehends the non-cancer cells facilitating the cancer growth and elaborates on the notable role of the CCR9-CCL25 chemokine axis in shaping the tumor microenvironment (TME), directly and via immune cells. Association of increased CCR9 and CCL25 levels in various tumors has demonstrated the significance of this axis as a tool commonly used by cancer to flourish. It is involved in attracting immune cells in the tumor and determining their fate via various direct and indirect mechanisms and, leaning the TME toward immunosuppressive state. Besides, elevated CCR9-CCL25 signaling allows survival and rapid proliferation of cancer cells in an otherwise repressive environment. It modulates the intra- and extracellular protein matrix to instigate tumor dissemination and creates a supportive metastatic niche at the secondary sites. Lastly, this chapter abridges the latest research efforts and challenges in using the CCR9-CCL25 axis as a cancer-specific target.

CXCR6-CXCL16 Axis Promotes Breast Cancer by Inducing Oncogenic Signaling.

Precise mechanisms underlying breast cancer (BrCa) metastasis are undefined, which becomes a challenge for effective treatments. Chemokine signaling instigates the trafficking of cancer cells in addition to leukocytes. This study aimed to ascertain the clinical and biological significance of the CXCR6/CXCL16 signaling axis in the pathobiology of BrCa. Our data show a higher expression of CXCR6 in BrCa cell lines and tissues. Stage-III BrCa tissues express significantly higher CXCR6 compared to stage-II tissues. The ligand, CXCL16, could remain tethered to the cell surface, and, after proteolytic shedding of the ectodomain, the N-terminal fragment is released, converting it to its oncogenic, soluble form. Like CXCR6, N-terminal CXCL16 and ADAM-10 were significantly higher in stage-III than stage-II, but no significant difference was observed in the C-terminal fragment of CXCL16. Further, stimulation of the CXCR6/CXCL16 axis activated Src, FAK, ERK1/2, and PI3K signaling pathways, as per antibody microarray analysis, which also underlie CXCL16-induced F-actin polymerization. The CXCR6/CXCL16 axis induces cytoskeleton rearrangement facilitating migration and invasion and supports BrCa cell survival by activating the PI3K/Akt pathway. This study highlights the significance of the CXCR6/CXCL16 axis and ADAM10 as potential therapeutic targets for advanced-stage BrCa.

Tribological Properties of Chromium Nitride on the Cylinder Liner under the Influence of High Temperature.

The chromium nitride coating is a hard coating used to improve the sliding friction and wear behavior and is applied to engine components in various operating conditions even at an elevated temperature. In this study, chromium nitride was deposited by a physical vapor deposition process onto the cast iron substrate. All tribological tests were performed on linear reciprocating tribometer with a stroke length of 5 mm in a dry condition at variable temperature levels of 28 °C, 100 °C, 200 °C, and of 300 °C corresponding to loads of 10 N, 20 N, 30 N, and 40 N against the cylinder liner material. The worn surfaces of chromium nitride(CrN) coatings after friction tests were analyzed by scanning electron microscope (SEM) and energy-dispersive spectroscopy (EDS). The results showed that friction coefficients (COF) ranged from 0.93 to 0.34 from room temperature to 300 °C against the cylinder liner material as a counter-body of 6 mm in diameter; higher temperature results in the positive tribological performance of CrN, with at least 0.34 COF at 300 °C. The wear mechanisms of CrN and counter-body surfaces are abrasive wear accompanied by the slight oxidation. This study guides the wear behavior of cylinder liner coatings in an environment similar to the engine.

Nucleophilic Acylation with Aromatic Aldehydes to 2 Bromoacetonitrile: An Umpolung Strategy for the Synthesis of Active Methylene Compounds.

BACKGROUND: A novel one-pot N-heterocyclic carbene (NHC)-catalysed acylation of 2- bromoacetonitrile with aromatic aldehydes is reported. The protocol involves carbonyl umpolung reactivity of aldehydes in which the carbonyl carbon attacks nucleophilically (as d1 nucleophile) on the electrophilic terminal of 2-bromoacetonitrile to afford 3-aryl-3-oxopropanenitrile. The salient features of this procedure are short reaction time, operational simplicity, ambient temperature, no by-product formation and high yields. MATERIALS AND METHODS: A flame-dried round bottom flask was charged with Imidazolium salts (3a) (0.20 mmol). Aldehyde 1a (1.0 mmol), 2-bromoacetonitrile 2 (1.0 mmol), and THF / t-BuOH 5 mL; 10:1) were added at positive nitrogen pressure followed by the addition of DBU (0.15 mmol) through stirring. The resulting yellow- orange solution was stirred at room temperature for 5-6 h. After completion of the reaction (TLC monitored), the reaction mixture was concentrated under reduced pressure. The product was purified using hexane / EtOAc (10:1) as an eluent to provide analytically pure compound 4a. Physical data of representative compounds and the NMR spectroscopic data are in agreement with the literature value. RESULTS AND DISCUSSION: The salient features of this procedure are short reaction time, operational simplicity, ambient temperature, no by-product formation and high yields. CONCLUSION: To sum up, we have developed a convenient, efficient and one-pot route for 3-oxo-3- phenylpropanenitrile synthesis from NHC promoted direct nucleophilic acylation of aromatic aldehydes using 2- bromoacetonitrile. This method provided a wide range of products and good yields. To best of our knowledge, this is the new report for the synthesis of 3-oxo-3-phenylpropanenitrile through NHC promoted nucleophilic acylation of aromatic aldehyde.

Chemoenzymatic, biomimetic total synthesis of (-)-rugulosin B, C and rugulin analogues and their biosynthetic implications.

Herein, we report the chemoenzymatic synthesis of a heterodimeric (-)-rugulosin B, homodimeric (-)-rugulosin C, and several rugulin analogues in three to four steps starting from anthraquinones. This work supports dimerization between variously substituted putative monomeric intermediates during the biosynthesis of naturally occurring (+)-rugulosin B and C.