Innovative Self-directed, Problem-oriented, Lifelong learning, Integrated Clinical case Exercise (SPLICE) modules promote critical thinking skills, early clinical exposure, and contextual learning among first professional-year medical students.

Medical education is undergoing various transformations to promote a more personalized and contextual way of learning. In light of this, the innovative "Self-directed, Problem-oriented, Lifelong learning, Integrated Clinical case Exercise" (SPLICE) modules were designed, implemented, and evaluated for medical students in the first professional year as a strategy for early clinical exposure in a collaborative and self-directed way of learning. This is a mixed methods study involving first-year medical students. Students were divided randomly into the control and the intervention groups. Six SPLICE modules were administered to the intervention while the control group followed the traditional curricula. The educational outcome was compared using an end-of-module assessment. In addition, 13-item and 8-item questionnaires were administered to students to evaluate the SPLICE and plenary sessions on a 5-point Likert scale. Furthermore, students' feedback was obtained on a 10-point rating scale and in in-depth small-group interviews. The majority of students perceived that the SPLICE module improved their communication and encouraged meaningful, active learning. Students found the plenary sessions to be well organized, with sufficient interaction with professionals. Students also gave excellent scores for feedback on SPLICE modules, demonstrating the effectiveness of the innovation. In terms of test scores used in assessing learning outcomes, the intervention group outperformed the control group (P < 0.0001). The innovative SPLICE curriculum facilitated early clinical exposure and active self-directed learning. Students perceived SPLICE modules to be highly helpful in terms of promoting meaningful learning and the future application of knowledge.NEW & NOTEWORTHY The very essence of this innovative "Self-directed, Problem-oriented, Lifelong learning, Integrated Clinical case Exercise" (SPLICE) curriculum is the team-based learning of integrated pre-, para-, and clinical learning objectives right from the first professional year of study serving as an early clinical exposure. This unique way of learning creates a holistic educational environment by combining both academic and professional development thereby empowering the next generation of physician leaders to take autonomy of their own learning strategies and emerge as competent lifelong learners.

"CARBGAME" (CARd & Board GAmes in Medical Education): a gamification innovation to foster active learning in biochemistry for medical students.

Diving into the realm of game-based learning, the "CARBGAME"(CARd & Board GAmes in Medical Education) is an innovative series of games that reimagines the way medical students learn complex but essential chapters. In the pilot study, there was a highly significant improvement in the academic performance of students in the chapter "Vitamins." All the students perceived CARBGAME to be highly rewarding in terms of creating engaging and meaningful learning experiences. Recognizing the benefit of games in medical education, we strongly recommend the implementation of CARBGAME for essential topics in physiology education to create a more dynamic and engaging learning environment for students.NEW & NOTEWORTHY "CARBGAME" (CARd & Board GAmes in Medical Education) creates a unique and fun-filled educational environment where students learn complex but essential medical chapters in a gamified manner using cards and boards. This customizable innovation is strengthened with fundamental educational principles to promote engaging and meaningful learning experiences for students.

"Aquilibria: The battle to balance"-a narrative card and board game on acid-base regulation for first-year medical students.

Recognizing the growing value of game-based learning in medical education, this study aims to evaluate the effectiveness of the innovation, "Aquilibria: The Battle to Balance," a creative narrative card and board game to help improve learners' understanding and application of the concepts of acid-base balance. In this mixed-method study, 120 first-year medical students participated. The innovation employed a card and board style integrated with a captivating story. Students were divided into small groups of six each with a facilitator. Following this, the posttest was conducted to compare the educational gain. Also, students' perceptions about the game were obtained using a 32-item questionnaire on a 5-point Likert scale. In addition to this, the confidence level among students to understand and interpret the concepts of acid-base regulation before and after the game was obtained using a 10-item questionnaire on a 5-point Likert scale. Furthermore, for qualitative data, short interviews with open-ended questions were conducted and thematic analysis was performed. The results showed a highly significant improvement in academic performance from a pretest score of 7.57 ± 1.07 (means ± SD) to 16.14 ± 1.80 in the posttest with a P value of <0.0001. There was a notable increase in confidence among learners after the game, and highly positive student feedback was received. These findings support the growing recognition of narrative game-based learning as a valuable and engaging strategy in medical education, offering a promising avenue for fostering deeper understanding and retention of complex medical concepts.NEW & NOTEWORTHY This innovation is a captivating blend of storytelling, cards, and board gameplay to facilitate the learning of acid-base regulation. This engaging game offers a wealth of questions and diverse case scenarios, allowing learners to repeatedly explore and grasp the intricacies of acid-base balance. What sets this game apart is its robust assessment strategy, supported by overwhelmingly positive feedback and marked academic improvement. This innovation is a must-have for students seeking a dynamic and effective learning experience.

EMBRACE (Empowering Medical students' skills in BReaking bAd news with Compassion and Empathy) module improves the skills of undergraduate medical students in effectively breaking the bad news: a case-control study.

Effective communication skills are pivotal in health care, particularly when conveying distressing information to patients and their families. However, medical education still lacks the adoption of a universal model that can be incorporated into the curricula to train and assess students in effectively communicating with patients. This study aims to assess the impact of training undergraduate medical students to deliver bad news effectively using the Empowering Medical students' skills in BReaking bAd news with Compassion and Empathy (EMBRACE) module. This randomized case-control study involved medical students from the first, second, and third professional years (study group, n = 75; control group, n = 75). For the study group, the EMBRACE modules were distributed. Then, a 1-hour training session on effectively delivering bad news was followed by a multiple-choice question test and objective structured clinical examination with response, interpretation, and communication skills stations. Participants' feedback was obtained on a five-point Likert scale. There was a highly significant improvement in knowledge and skills among the study group compared to controls with a P value less than 0.0001. Of the participants, 98.76% perceived that the training equipped them with practical skills, and 98.77% felt that the facilitator had demonstrated the steps of delivering bad news clearly and effectively. Only 4.44% of participants were confident in effectively interacting with patients before the session, and an overwhelming 81.11% gained confidence in their communication skills after the training. With demonstrated significant improvement in knowledge and skills, this study supports the adoption of EMBRACE modules in undergraduate medical education, ultimately improving patient experiences, doctor-patient relationships, and health outcomes.NEW & NOTEWORTHY The Empowering Medical students' skills in BReaking bAd news with Compassion and Empathy (EMBRACE) module is noteworthy for its holistic approach to training medical students in the delicate art of delivering distressing news to patients. It not only incorporates the evidence-based setting, perception, invitation, knowledge, emotions, and strategy (SPIKES) method but also distinguishes itself by providing real-life conversation examples and self-assessment cases, which make the training highly relatable and practical for students to actively engage in their learning and personal development.

"METAPAD" (METAbolic PAthways Decoded) - a gaming innovation to ease the complexity of metabolic pathways by promoting self-directed, active, participatory learning in small groups.

BACKGROUND: In medical education, the conventional didactic lectures make the learning process tedious and cause disinterest among students. To overcome this, an effective experiential learning integrated with game-based approach that intends to make the learning process fun filled, interesting and enhance the active participation of students to understand complex topics in a simple and optimum manner should be adopted. OBJECTIVES: The purpose of this study is to assess the efficiency of a puzzle-based innovation, METAPAD (METAbolic PAthways Decoded) in understanding the complexity of biochemical pathways by enhancing the self-directed learning of students through active engagement in small groups METHODS: In this mixed-method study, 103 first professional year medical students in small groups were enrolled for the METAPAD gaming puzzle-based learning activity. The puzzles were integrated with a relevant clinical case study. Decoding the puzzle after identification of the metabolic pathway involved in the case was conducted in level 1,2 and 3 with increasing complexity of puzzles at every level. Following the puzzle activity, A 21-item questionnaire was administered to evaluate the usefulness of the innovation and students' perceptions towards different learning styles. Also, students' feedback was obtained through personal interviews for qualitative analysis and thematic analysis was performed. RESULTS: One hundred and three first year undergraduate medical students participated in the study. Most of the students perceived the METAPAD gaming puzzle to be an effective and innovative style of learning. There was not any significant association between age, gender and acceptance towards the METAPAD gaming puzzle. The predominant type of learning style among the students was multimodal (49.5%). Also, there was no great influence of the learning styles on the overall perception towards the METAPAD gaming puzzle. However, learners emphasized the need to focus more while solving the puzzles. CONCLUSION: Students perceive the METAPAD gaming puzzle as an actively engaging teaching-learning method that enhances their creativity, critical thinking and problem-solving abilities. It promotes self-directed learning of complex pathways in biochemistry which helps in remembering and recalling information and improves their learning skills.

Effects of polyphenols on ncRNAs in cancer-An update.

In recent years, oncotherapy has received considerable attention concerning plant polyphenols. Increasing evidence suggests that because of the efficiency of polyphenols, they may have anti-tumour effects in various cancers. However, their regulatory structures remain elusive. Long non-coding RNAs (lncRNAs) have been identified in the regulation of various forms of tumorigenesis and tumour development. Long non-coding RNAs have recently emerged as regulatory eukaryotic transcripts and therapeutic targets with important and diverse functions in health and diseases. LncRNAs may be associated with the initiation, development, and progression of cancer. This review summarizes the research on the modulatory effects of IncRNAs and their roles in mediating cellular processes. The mechanisms of action of polyphenols underlying their therapeutic effects on cancers are also discussed. Based on our review, polyphenols might facilitate a significant epigenetic modification as part of their tissue- and/or cell-related biological effects. This finding may be attributed to their interaction with cellular signalling pathways involved in chronic diseases. Certain lncRNAs might be the target of specific polyphenols, and some critical signalling processes involved in the intervention of cancers might mediate the therapeutic roles of polyphenols.

SARS-CoV-2 infection increases risk of acute kidney injury in a bimodal age distribution.

BACKGROUND: Hospitalized patients with SARS-CoV2 develop acute kidney injury (AKI) frequently, yet gaps remain in understanding why adults seem to have higher rates compared to children. Our objectives were to evaluate the epidemiology of SARS-CoV2-related AKI across the age spectrum and determine if known risk factors such as illness severity contribute to its pattern. METHODS: Secondary analysis of ongoing prospective international cohort registry. AKI was defined by KDIGO-creatinine only criteria. Log-linear, logistic and generalized estimating equations assessed odds ratios (OR), risk differences (RD), and 95% confidence intervals (CIs) for AKI and mortality adjusting for sex, pre-existing comorbidities, race/ethnicity, illness severity, and clustering within centers. Sensitivity analyses assessed different baseline creatinine estimators. RESULTS: Overall, among 6874 hospitalized patients, 39.6% (n = 2719) developed AKI. There was a bimodal distribution of AKI by age with peaks in older age (≥60 years) and middle childhood (5-15 years), which persisted despite controlling for illness severity, pre-existing comorbidities, or different baseline creatinine estimators. For example, the adjusted OR of developing AKI among hospitalized patients with SARS-CoV2 was 2.74 (95% CI 1.66-4.56) for 10-15-year-olds compared to 30-35-year-olds and similarly was 2.31 (95% CI 1.71-3.12) for 70-75-year-olds, while adjusted OR dropped to 1.39 (95% CI 0.97-2.00) for 40-45-year-olds compared to 30-35-year-olds. CONCLUSIONS: SARS-CoV2-related AKI is common with a bimodal age distribution that is not fully explained by known risk factors or confounders. As the pandemic turns to disproportionately impacting younger individuals, this deserves further investigation as the presence of AKI and SARS-CoV2 infection increases hospital mortality risk.

Thyroid-Stimulating Hormone Favors Runx2-Mediated Matrix Mineralization in HOS and SaOS2 Cells: An In Vitro and In Silico Approach.

Osteoporosis is a skeletal disease that is both systemic and silent characterized by an unbalanced activity of bone remodeling leading to bone loss. Rising evidences demonstrate that thyroid stimulating hormone (TSH) has an important role in the regulation on the metabolism of bone. However, TSH regulation on human osteoblast essential transcriptional factors has not been identified. Current study examined the role of TSH on human osteoblastic Runx2 expression and their functional genes by in vitro and in slico analysis. Human osteoblast like (HOS and SaoS-2) cells were cultured with DMEM and treated with hTSH at the concentration of 0.01 ng/mL and 10 ng/mL. After treatment, osteoblastic Runx2 and IGF-1R beta expression were studied using RT-PCR and western blot analysis. TSH treatment induced osteoblastic essential transcriptional factor, Runx2 in HOS and SaOS2 cells on 48 h duration and elevated the expression of IGF-IR ß gene and Protein in SaoS-2 cells. TSH also promotes Runx2 responsive genes such as ALP, Collagen and osteocalcin in SaOS2 cells on day 2 to day 14 of 10 ng/mL of treatment and favors' matrix mineralization matrix in these cells. In addition, TSH facilitated human osteoblastic cells to mineralize their matrix confirmed by day 21 of alizarin red calcium staining. In silico study was performed to check CREB and ELK1 interaction with Runx2. Results of in silico analysis showed that TSH mediated signalling molecules such as CREB and ELK1 showed interaction with Runx2 which involve in osteobalstic gene expression and differentiation. Present findings confirm that TSH promotes Runx2 expression, osteoblastic responsive genes and bone matrix formation.

A Comprehensive Review on Therapeutic Perspectives of Phytosterols in Insulin Resistance: A Mechanistic Approach.

Natural products in the form of functional foods have become increasingly popular due to their protective effects against life-threatening diseases, low risk of adverse effects, affordability, and accessibility. Plant components such as phytosterol, in particular, have drawn a lot of press recently due to a link between their consumption and a modest incidence of global problems, such as Type 2 Diabetes mellitus (T2DM), cancer, and cardiovascular disease. In the management of diet-related metabolic diseases, such as T2DM and cardiovascular disorders, these plant-based functional foods and nutritional supplements have unquestionably led the market in terms of cost-effectiveness, therapeutic efficacy, and safety. Diabetes mellitus is a metabolic disorder categoriszed by high blood sugar and insulin resistance, which influence major metabolic organs, such as the liver, adipose tissue, and skeletal muscle. These chronic hyperglycemia fallouts result in decreased glucose consumption by body cells, increased fat mobilisation from fat storage cells, and protein depletion in human tissues, keeping the tissues in a state of crisis. In addition, functional foods such as phytosterols improve the body's healing process from these crises by promoting a proper physiological metabolism and cellular activities. They are plant-derived steroid molecules having structure and function similar to cholesterol, which is found in vegetables, grains, nuts, olive oil, wood pulp, legumes, cereals, and leaves, and are abundant in nature, along with phytosterol derivatives. The most copious phytosterols seen in the human diet are sitosterol, stigmasterol, and campesterol, which can be found in free form, as fatty acid/cinnamic acid esters or as glycosides processed by pancreatic enzymes. Accumulating evidence reveals that phytosterols and diets enriched with them can control glucose and lipid metabolism, as well as insulin resistance. Despite this, few studies on the advantages of sterol control in diabetes care have been published. As a basis, the primary objective of this review is to convey extensive updated information on the possibility of managing diabetes and associated complications with sterol-rich foods in molecular aspects.

Understanding the binding conformation of ceftolozane/tazobactam with Metallo-ß-lactamases VIM-5 and IMP-7 of Pseudomonas aeruginosa: A molecular docking and virtual screening process.

Pseudomonas aeruginosa (P. aeruginosa) is one of the community-acquired and healthcare-associated infections causing organisms. It has become resistant to most of the available antibiotics and is termed multi-drug resistance (MDR). There are a limited number of antibiotics are available to treat such MDR organism causing infections. The ceftolozane/tazobactam is one among the combination drug therapy (CDT) prescribed for the treatment of MDR causing infections. The resistance for the same CDT was observed in the MDR P. aeruginosa harboring VIM-5 and IMP-7 Metallo beta (ß)-lactamases (MBLs). To explore the resistance mechanism at the molecular level, docking studies were carried out for antibiotics against VIM-5 and IMP-7 MBLs. The Zn2 metal ions carry out the nucleophile attack on the carbonyl carbon of the ß-lactam ring along with conserved water molecules. To find lead compounds against the MBLs, a virtual screening process was carried out. We have employed MODELLER for structure modeling, AutoDock for molecular docking and AutoDock Vina, Molinspiration, PASS prediction & admetSAR in virtual screening. The search of low binding energy ceftolozane analogs against VIM-5 and IMP-7 MBLs has resulted in the ZINC000029060075 and ZINC000009163636 analogs. Similarly, the screening of high binding energy inhibitors against VIM-5 and IMP-7 MBLs has resulted in ZINC000003831503 and ZINC000000897247 tazobactam analogs respectively. The ADMET prediction results in the non-toxicity of the lead compounds. Our study may provide new insights for the scientist who are designing novel drugs against MDR P. aeruginosa causing infections.

Eugenol-piperine loaded polyhydroxy butyrate/polyethylene glycol nanocomposite-induced apoptosis and cell death in nasopharyngeal cancer (C666-1) cells through the inhibition of the PI3K/AKT/mTOR signaling pathway.

Nasopharyngeal cancer is a malignancy developing from the nasopharynx epithelium due to smoking and nitrosamine-containing foods. Nasopharyngeal cancer is highly endemic to Southeast Asia. Eugenol and piperine have shown many anticancer activities on numerous cancer types, like colon, lung, liver, and breast cancer. In this study, we amalgamated eugenol and piperine loaded with a polyhydroxy butyrate/polyethylene glycol nanocomposite (Eu-Pi/PHB-PEG-NC) for better anticancer results against nasopharyngeal cancer (C666-1) cells. In the current study, nasopharyngeal cancer cell lines C666-1 were utilized to appraise the cytotoxic potential of Eug-Pip-PEG-NC on cell propagation, programmed cell death, and relocation. Eu-Pi/PHB-PEG-NC inhibits cellular proliferation on C666-1 cells in a dose-dependent manner, and when compared with 20 µg/ml, 15 µg/ml of loaded mixture evidently restrained the passage aptitude of C666-1 cells, this was attended with a downregulated expression of mitochondrial membrane potential. Treatment with 15 µg/ml Eu-Pi/PHB-PEG-NC suggestively amplified cell apoptosis in the C666-1 cells. Furthermore, its cleaved caspase-3, 8, and 9 and Bax gene expression was augmented and Bcl-2 gene expression was diminished after Eu-Pi/PHB-PEG-NC treatment. Additionally, our data established that the collective effect of Eu-Pi/PHB-PEG-NC loaded micelles inhibited the expansion of C666-1 cells augmented apoptosis connected with the intrusion of PI3K/Akt/mTOR signaling pathway.

Anti-inflammatory effects of rhaponticin on LPS-induced human endothelial cells through inhibition of MAPK/NF-κß signaling pathways.

The untreated systemic chronic inflammation leads to autoimmune diseases, hyperglycemia, cardiovascular diseases, type 2 diabetes, hypertension, osteoporosis, and so on. Phytochemicals effectively inhibit the inflammation, and numerous studies have proved that the phytocomponents possess anti-inflammatory property via inhibiting the cyclooxygenase and lipoxygenase signaling pathways. Rhaponticin is one such phytochemical obtained from the perennial plant Rheum rhaponticum L. belonging to Polygonaceae family. We assessed the anti-inflammatory potency of rhaponticin in endothelial cells induced with lipopolysaccharides (LPS). Four different endothelial cells induced with LPS were treated with rhaponticin and assessed for the nitric oxide generation. The cytotoxic potency of rhaponticin was evaluated in endothelial cells using the 3-(4,5-dimethylthizaol-2yl)-2,5-diphenyl tetrazolium bromide assay. The tumor necrosis factor-α (TNF-α) synthesis was quantified using the commercially available assay kit. The inflammatory signaling protein gene expression of TNF-α, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), and interleukin-1ß (IL-1ß) was analyzed with quantitative polymerase chain reaction (PCR) analysis. The gene expression of NADPH oxidase (NOX) cytoplasmic catalytic subunits gp91phox , p47phox , and p22phox was assessed with real-time PCR analysis. Finally, to confirm the anti-inflammatory potency of rhaponticin, the nuclear factor kappa B (NFκB) and mitogen-activated protein kinase (MAPK) signaling protein expression was analyzed with immunoblotting analysis. Rhaponticin treatment significantly decreased the levels of nitric oxide and TNF-α synthesis in LPS-induced endothelial cells. It significantly decreased the gene expression of inflammatory proteins and NOX signaling protein. The protein expression of NFκB and MAPK signaling proteins was drastically decreased in rhaponticin-treated endothelial cells induced with LPS. Overall, our results confirm that rhaponticin effectively inhibited the inflammation triggered by LPS in endothelial cells via downregulating iNOS, COX2, and NFκB and MAPK signaling pathways.

Arbutin exerts anticancer activity against rat C6 glioma cells by inducing apoptosis and inhibiting the inflammatory markers and P13/Akt/mTOR cascade.

Gliomas are a type of brain cancer that occurs in the supporting glial cells of the brain. It is highly malignant and accounts for 80% of brain tumors with high mortality and morbidity. Phytomedicines are potent alternatives for allopathic drugs which cause side effects. They have been used from ancient times by traditional Chinese, Ayurveda, and Siddha medicine. Arubtin is a glycoside phytochemical extracted from plants and belongs to the family of Ericaceae. Arbutin possesses various pharmacological properties such as anti-inflammatory, antioxidant, antitumor, and so on. Hence in the present study, we analyzed the anticancer potency of arbutin against rat C6 glioma cells. Rat C6 glioma cells were procured from American Type Culture Collection and the cells were cultured in Roswell Park Memorial Institute-1640 medium. To assess the cytotoxicity effect of the arbutin against C6 glioma cells, an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test was performed with different doses from 10 to 60 µM. Arbutin effectively induced apoptosis in the cells and the IC50 dose was obtained at 30 µM. For further studies, we selected the 30 µM IC50 dose and a higher dose of 40 µM. Reactive oxygen species (ROS) generated were analyzed with DCFDA/H2DCFDA stain and the destruction of mitochondrial membrane permeability which is the initiator of apoptosis was analyzed with a cationic stain Rhodamine 123. Dual staining with acridine orange and ethidium bromide was performed to assess the viable and dead cells. Cell adhesion properties of glioma cells were analyzed with Matrigel assay. The apoptotic, inflammatory, and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling molecules were analyzed with quantitative polymerase chain reaction (qPCR) analysis to confirm the anticancer effect of arbutin. Arbutin generated excessive ROS and disrupted the mitochondrial membrane, which induced apoptosis in cells, it also inhibited the cell adhesion property of C6 glioma cells. qPCR analysis clearly indicates arbutin increases the apoptotic genes and decreased the inflammatory and PI3K/mTOR signaling molecules. Overall, our results authentically confirm that arbutin can be a potent alternative for treating glioma.

Knowledge on cervical cancer and perceived barriers to the uptake of HPV vaccination among health professionals.

BACKGROUND: Despite the fact that cervical cancer is preventable and curable in the early stages, it still remains to be a major public health problem in India. This study was conducted to assess the knowledge and awareness regarding the Human Papilloma Virus (HPV) vaccination among health care professionals working in a tertiary care hospital in urban India. METHODS: To this aim, we conducted a cross-sectional study among 318 health care professionals working in tertiary hospitals across Chennai, Tamil Nadu, India. Our research group designed a structured questionnaire with 31 items to assess the knowledge and attitudes on cervical cancer, its prevention, and HPV vaccination. RESULTS: Among the 318 respondents, 90.6% were aware of cervical cancer, 83.3% were aware that PAP (Papanicolaou) smear test detects cervical cancer, and 86.2% of the respondents knew that HPV causes cervical cancer. 29.2% of the eligible respondents underwent the screening against cervical cancer, and 19.8% of the study participants were vaccinated for HPV. Only 34.9% know that the HPV vaccine could be given to boys. The most common reason for not being vaccinated against HPV was the lack of awareness. In our study, 77.2% of the respondents were willing to be vaccinated and recommend HPV vaccination to their family members. CONCLUSION: From this study, it was evident that there is a lack of awareness about HPV vaccination and its importance in preventing cervical cancer among healthcare professionals. Our finding clearly establishes the need to devise intervention programs to promote vaccination against HPV and periodical screening for cervical cancer among healthcare professionals.

Application of proteometric approach for identification of functional mutant sites to improve the binding affinity of anticancer biologic trastuzumab with its antigen human epidermal growth factor receptor 2.

The aim of the present study was to develop a linear regression model aiding to a quick scan of the most important sites for mutation of an anticancer biologic trastuzumab. The important sites identified on trastuzumab can be used to carry out site-directed mutagenesis to improve the binding affinity of the drug towards its antigen, human epidermal growth factor receptor 2 (HER2). This will lead to low dosage requirement of the drug for treating cancer patients, which in turn help to cut the cost and combat development of resistance. A quantitative structure-activity relationship (QSAR) model was built by multiple linear regressions using genetic algorithm-based feature selection (GA-MLR) method using 48 dependent variables (dissociation constant Kd ) and 226 independent variables (theoretical descriptors generated using a proteometrics approach). The final QSAR model selected in the study was more on the basis of ability to predict accurately independent test data and generalization ability of the model rather than mere statistical significance of the model. With combined analysis of descriptors presented in final QSAR model and most frequent descriptors pooled from all solution models, it was demonstrated that the modeling procedure was able to bring on the factors important for antigen-antibody interactions with an example of HER2-trastuzumab interaction reported in previous experimental studies. This paper will allow the prediction of the most preferable site to mutate for improving the binding affinity of trastuzumab with HER2 and also will be helpful in selecting most preferable amino acids to substitute in the selected site for mutations. This is the novel report on proteometrics approach with autocorrelation formalism for antibody engineering, which can be extended to other antibody-antigen pairs.

Zingerone induced caspase-dependent apoptosis in MCF-7 cells and prevents 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in experimental rats.

Breast cancer is a prevalent of tumoregenesis in women and reports for the maximum mortality and morbidity in the global. Ginger (Zingiber officinale) is the mainly widespread spice and herbal remedies used in the world. Since antique periods, ginger has been used in Greece, India and China for the curing of upset stomach, nausea, diarrhea, colds, and headaches. The current work was planned to explore the anticancer properties of zingerone (ZO) toward 7,12-dimethylbenz(a)anthracene (DMBA)-treated mammary carcinogenesis in Sprague-Dawley (SD) rats and MCF-7 mammary cancer cells. The mammary carcinogenesis was produced through a single dosage of DMBA (20 mg/kg bwt) mixed in soya oil (1 mL) administrated intragastrically with a gavage. We found improved concentrations of lipid peroxidation (LOOH and TBARS), carcinoembryonic antigen, lowered levels of enzymatic (CAT, GPx, and SOD), and nonenzymatic (vitamin E, GSH, and vitamin C) antioxidant in mammary tissues and plasma of DMBA-induced cancer bearing animals. Moreover, augmented concentrations of phase I (Cyt-b5 and CYP450 ) and reduced levels of phase II (GR and GST) detoxification microsomal proteins in mammary tissues were noticed. ZO administrations significantly reverted back to all these parameters in this way, showing efficient of anticancer effect. Furthermore, our in vitro study also supported the anticancer effect of the treatment of ZO were noticed loss of cell viability, improved reactive oxygen species formation, and reduced MMP. Furthermore, the status of apoptosis proteins such as Bcl-2, Bax, and Bid expressions was determined by using Western blot analysis techniques. Overall, these results proposed the anticancer effect of ZO toward DMBA-induced mammary cancer in SD animals and Michigan cancer foundation-7 mammary cancer cells.