Characterizing the Anti-Cancer Efficacy of Rosemary Extract on Human Melanoma Cells

Melanoma is the deadliest form of skin cancer and the 19th most commonly occurring cancer in men and women. Current therapies for treating melanoma include surgery, radiotherapy, chemotherapy, and immunotherapy. Surgeries are primarily helpful at early stages and invasive, while the other treatment options are often accompanied by many side effects due to their toxicity to healthy tissues. Hence, there is a need for the development of more efficacious and less toxic treatments. Historically, several Natural Health Products have been used as non-toxic and medicinal herbs for multiple illnesses, so they are good candidates for anti-cancer agents. In particular, studies have shown that Rosemary Extract (RE), derived from Salvia rosmarinus, has demonstrated anti-cancer properties on many cancer types. However, the level and mechanisms of cell death have not yet been elucidated in both the A375 and G361 human melanoma cell lines. As well, supplemental trials, which assess efficacy and toxicity of RE in combination with chemotherapeutics have not been done for melanoma. Hence, we have characterized the in-vitro RE efficacy in the A375 and G361 cell lines alone and in combination with standard chemotherapeutics used for treatment. The results indicate that RE induces apoptosis at relatively low dosages alone and in a dose-dependent manner. Furthermore, when RE is used in combination with current treatments, there is no negative interaction and even an anticipated positive interaction following further trials. Thus, RE is a good potential candidate for the treatment of this deadly illness affecting thousands of people around the world

ROLE OF SPORTS IN MAKING A LEADER

ABSTRACT The article establishes a link between how sports and games develop the leadership qualities and maintain the body and mind coordination in individuals. The nature of the work is theoretical. The concept of leadership is a social notion. It was formally developed during the 1960s to emphasize the ability of the leader to influence the scope in his organization in order to achieve the organizational goals. It emphasizes the interactional processes involved in the achievement of goals. Each manager in the field of education is called upon, everyday to display leadership in a variety of forms. Practice of leadership is, in all forms, essentially an interpersonal activity. Sports activities, SUPW (Socially useful productive work), co-curricular activities, administrative activities etc. have been acclaimed for stimulating the soul out. Sports can easily develop the leadership qualities in one's personality. Personality is a term used to characterize the individual that emerges as a person grows, matures, and reacts to the thousands of environmental stimuli that surround him. The learning of social values, and particularly sportsmanship, must be a part of the purpose of the individual; its results must be recognized and be made satisfying if learning is to take place. Sports and games occupy a good amount of time in the lives of many people. Sports participation gives ample opportunities to learn ethical values and sportsmanship qualities. On the contrary, there are many occasions in sports where children learn to be rude or show unsportsman like behavior. Much depends on the goals and philosophy of the training programme, the coach and the outlook of the parents. But with proper direction one can develop desirable qualities such as leadership, discipline, determination, hard work, fair play, cooperation and mutual respect. It is clear from the literature that the development of an acceptable level of physical fitness helps to attain healthy personality and physio-psychological characteristics. Hence, a better healthy living is universally accepted as a goal of a physical education programme. As quoted by Swami Vivekananda, a great saint of India: "you will be nearer to heaven through physical activities" KEY WORDS: Sports in making, a leader

Some New Correlation Coefficient Measures Based on Fermatean Fuzzy Sets using Decision Making Approach in Pattern Analysis and Supplier Selection

Fermatean fuzzy set (FFS) is an effective tool to depict expert reasoning information in the decision‐making process than fuzzy sets (FS), intuitionistic fuzzy sets (IFS), and Pythagorean fuzzy sets (PFS). Keeping in mind the importance of correlation coefficient and application in medical diagnosis, decision making and pattern recognition, several studies on correlation coefficient measures have been proposed in the literature. As there does not exist any study concerning correlation coefficient measures for FFS, in this communication, we propose novel entropy-correlation measures for Fermatean fuzzy sets and applied it decision making problems of pattern analysis and multi-criteria decision making for supplier selection. With the help of proposed correlation coefficient, we establish some weighted measures for FFS. Using numerical computations, we determine the efficacy of the suggested measures over other measures. The aim of this study is to propose a novel and efficient methodology for evaluation of supplier’s selection with uncertain information. Finally, we establish the comparative study of our developed measures over the existing correlation coefficient measures. The analysis showed that the suggested methodology is reliable, flexible, and consistent with the existing techniques

Transglutaminases and Obesity in Humans: Association of F13A1 to Adipocyte Hypertrophy and Adipose Tissue Immune Response

Transglutaminases TG2 and FXIII-A have recently been linked to adipose tissue biology and obesity, however, human studies for TG family members in adipocytes have not been conducted. In this study, we investigated the association of TGM family members to acquired weight gain in a rare set of monozygotic (MZ) twins discordant for body weight, i.e., heavy–lean twin pairs. We report that F13A1 is the only TGM family member showing significantly altered, higher expression in adipose tissue of the heavier twin. Our previous work linked adipocyte F13A1 to increased weight, body fat mass, adipocyte size, and pro-inflammatory pathways. Here, we explored further the link of F13A1 to adipocyte size in the MZ twins via a previously conducted TWA study that was further mined for genes that specifically associate to hypertrophic adipocytes. We report that differential expression of F13A1 (ΔHeavy–Lean) associated with 47 genes which were linked via gene enrichment analysis to immune response, leucocyte and neutrophil activation, as well as cytokine response and signaling. Our work brings further support to the role of F13A1 in the human adipose tissue pathology, suggesting a role in the cascade that links hypertrophic adipocytes with inflammation

Reducing Carbon Emissions: An Analysis of Smart City Initiatives and the Carbon Reduction Test

The need to cut carbon emissions in cities have become more pressing in an age of unparalleled urbanization and climate change. Using both quantitative and qualitative analysis, this study looks at how smart city efforts affect the decrease of carbon emissions. Carbon Reduction Test results and comparative studies show that smart cities with a comprehensive approach—including renewable energy use, energy-efficient buildings, public transportation upgrades, green energy projects, waste management enhancements, and energy-efficient transportation—achieved significant carbon emission reductions. These results demonstrate the transformational potential of smart cities in supporting international sustainability efforts and the efficacy of diverse techniques in reducing the urban carbon footprint

Endogenous Replication Stress in Mother Cells Leads to Quiescence of Daughter Cells.

Mammalian cells have two fundamentally different states, proliferative and quiescent, but our understanding of how and why cells switch between these states is limited. We previously showed that actively proliferating populations contain a subpopulation that enters quiescence (G0) in an apparently stochastic manner. Using single-cell time-lapse imaging of CDK2 activity and DNA damage, we now show that unresolved endogenous replication stress in the previous (mother) cell cycle prompts p21-dependent entry of daughter cells into quiescence immediately after mitosis. Furthermore, the amount of time daughter cells spend in quiescence is correlated with the extent of inherited damage. Our study thus links replication errors in one cell cycle to the fate of daughter cells in the subsequent cell cycle. More broadly, this work reveals that entry into quiescence is not purely stochastic but has a strong deterministic component arising from a memory of events that occurred in the previous generation(s).</p

Role of Human Oral Microbiome in Diseases

The human oral microbiome represents a diverse and intricate ecosystem comprising bacteria, fungi, viruses, and protozoa. It plays a vital role in numerous physiological processes, ranging from digestion to immunity. Recent research endeavors have focused on delineating the composition and functions of the oral microbiome. Changes in the oral microbiome have been associated with both oral diseases (such as dental caries, periodontitis, halitosis) and systemic conditions (including cardiovascular disease, diabetes, and cancer). Despite significant advancements, numerous questions about the role of the oral microbiome in health and disease remain unanswered. Further research is imperative to explore the intricate interactions between the oral microbiome and other microbiomes within the body. Additionally, there is a need to develop targeted interventions capable of selectively modulating the oral microbiome without disrupting other beneficial microorganisms. In summary, delving into the study of the human oral microbiome has the potential to revolutionize our comprehension of health and disease, opening avenues for innovative approaches to preventive and therapeutic medicine

Synergistic combination of cytotoxic chemotherapy and cyclin-dependent kinase 4/6 inhibitors in biliary tract cancers

Background and aims: Biliary tract cancers (BTCs) are uncommon, but highly lethal, gastrointestinal malignancies. Gemcitabine/cisplatin is a standard-of-care systemic therapy, but has a modest impact on survival and harbors toxicities, including myelosuppression, nephropathy, neuropathy, and ototoxicity. Whereas BTCs are characterized by aberrations activating the cyclinD1/cyclin-dependent kinase (CDK)4/6/CDK inhibitor 2a/retinoblastoma pathway, clinical use of CDK4/6 inhibitors as monotherapy is limited by lack of validated biomarkers, diffident preclinical efficacy, and development of acquired drug resistance. Emerging studies have explored therapeutic strategies to enhance the antitumor efficacy of CDK4/6 inhibitors by the combination with chemotherapy regimens, but their mechanism of action remains elusive.Approach and results: Here, we report in vitro and in vivo synergy in BTC models, showing enhanced efficacy, reduced toxicity, and better survival with a combination comprising gemcitabine/cisplatin and CDK4/6 inhibitors. Furthermore, we demonstrated that abemaciclib monotherapy had only modest efficacy attributable to autophagy-induced resistance. Notably, triplet therapy was able to potentiate efficacy through elimination of the autophagic flux. Correspondingly, abemaciclib potentiated ribonucleotide reductase catalytic subunit M1 reduction, resulting in sensitization to gemcitabine.Conclusions: As such, these data provide robust preclinical mechanistic evidence of synergy between gemcitabine/cisplatin and CDK4/6 inhibitors and delineate a path forward for translation of these findings to preliminary clinical studies in advanced BTC patients.</p