The Role of Apoptosis as a Double-Edge Sword in Cancer

The pathogenesis of many diseases is most closely related to inappropriate apoptosis (either too little or too much) and cancer is one of the situations where too little apoptosis happens, leading to malignant cells that highly proliferate. Defects at any points along apoptotic pathways may lead to malignant transformation of the affected cells, tumor metastasis, and resistance to anti-cancer drugs. Several major molecular mechanisms are involved in the evasion of apoptosis in cancer initiation and progression. Bcl-2 family of proteins and caspases are the central players in the apoptotic mechanism and regulate cell death. Their imperfections cause to the deficient apoptotic signaling and thereby the inadequate apoptosis in cancer cells and eventually carcinogenesis. Strategies targeting these master regulators in carcinoma cells has been a major focus of interest in cancer studies. Therefore, despite being the cause of problem, apoptosis can be targeted in cancer therapy. This chapter provides a comprehensive review of apoptotic cell death and how deficiencies in apoptotic master regulators, caspases and Bcl-2 family proteins, influence carcinogenesis and can be targeted in cancer treatment

Variable fractional power‐least mean square based control algorithm with optimized PI gains for the operation of dynamic voltage restorer

Abstract The operation of Dynamic Voltage Restorer has been studied for the mitigation of supply voltage disturbances like sag, swell, distortions, and unbalances. A Dynamic Voltage Restorer with three single‐phase Voltage Source Converters has been implemented for this purpose. Dynamic Voltage Restorer's compensation capability has been evaluated while introducing the above‐said voltage related disturbances in the supply by different means. A control algorithm named Variable Fractional Power‐Least Mean Square has been proposed for generating the load reference voltage for Dynamic Voltage Restorer. Variable Fractional Power‐Least Mean Square extracts the fundamental active and reactive component out of non‐ideal supply voltage and is thus, used in generating reference load voltage. This algorithm is more robust with respect to disturbance due to variable step size and is computationally less expensive. In addition, an optimization‐based approach has been proposed to estimate the approximate values of PI control gains. For this reason, a population‐based optimization method known as Sine Cosine Optimization has been used. The added feature of the optimization method is the reduction of computational time as compared to conventional PI controller tuning. A model of Dynamic Voltage Restorer using Variable Fractional Power‐Least Mean Square control algorithm with Sine Cosine Optimization tuned PI gains has been built in MATLAB Simulink as well as a reduced scale experimental prototype and their results have been presented with discussion

Clint Relationships Through Mobile Crm In Organized Retail Outlets

Versatile Customer Relationship Management (mCRM) framework is one of the late progressions in CRM frameworks. Late years, clients utilizing cell telephone have displayed a quickly developing on quality included administrations, SMS and data administrations. Progresses in innovation have changed the path in which the retail division conducts business and are progressively furnishing client with more prominent accommodations. The reason for this paper a study on overseeing client connections through mCRM in sorted out retail outlets talks about methodologies received and headways mCRM work viably. Portable CRM elevates fulfillment to clients through the versatile medium on correspondence. The exploration paper brought about Mobile client relationship administration is an effective apparatus that will make awesome changes, investment funds and advantages Mobile-CRM framework low expenses and an incredible effect on the consumer loyalty for sorted out retail outlets. Retailers pick up an upper hand and enhance client relationship administration by Mobile CRM

A Case Study Of: Clint Relationship Management (CRM) Practices In Selected Organized Retail Outlets

Today in the profoundly aggressive business sector, expanding client requests retail outlets understand the significance of client relationship administration. The absence of comprehension on Customer Relationship Management (CRM) is dependably a worry among the administration suppliers particularly retail outlets, retailers have their own specific manner of dealing with their associations with the clients. Under this contextual analysis of CRM Practices in Selected sorted out retail outlets in Indore city examines about systems embraced, retail outlets can hold the client relationship. Comprehend the commitment of CRM of the retail outlets regarding its goals. The point of this contextual investigation discovering and distinguish these issues sway on client desires through actualized CRM retail outlets can enhance the association with clients

The curcumin analogue 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one induces apoptosis and downregulates E6 and E7 oncogene expression in HPV16 and HPV18-infected cervical cancer cells

In an effort to study curcumin analogues as an alternative to improve the therapeutic efficacy of curcumin, we screened the cytotoxic potential of four diarylpentanoids using the HeLa and CaSki cervical cancer cell lines. Determination of their EC50 values indicated relatively higher potency of 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one (MS17, 1.03 ± 0.5 μM; 2.6 ± 0.9 μM) and 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one (MS13, 2.8 ± 0.4; 6.7 ± 2.4 μM) in CaSki and HeLa, respectively, with significantly greater growth inhibition at 48 and 72 h of treatment compared to the other analogues or curcumin. Based on cytotoxic and anti-proliferative activity, MS17 was selected for comprehensive apoptotic studies. At 24 h of treatment, fluorescence microscopy detected that MS17-exposed cells exhibited significant morphological changes consistent with apoptosis, corroborated by an increase in nucleosomal enrichment due to DNA fragmentation in HeLa and CaSki cells and activation of caspase-3 activity in CaSki cells. Quantitative real-time PCR also detected significant down-regulation of HPV18- and HPV16-associated E6 and E7 oncogene expression following treatment. The overall data suggests that MS17 treatment has cytotoxic, anti-proliferative and apoptosis-inducing potential in HPV-positive cervical cancer cells. Furthermore, its role in down-regulation of HPV-associated oncogenes responsible for cancer progression merits further investigation into its chemotherapeutic role for cervical cance

Validation of Gender Friendly Breastfeeding Knowledge scale among young adults

Introduction: Breastfeeding is the most effective intervention to improve child health. Young adults, both genders play an important role in society supporting breastfeeding as they will be stepping towards parenthood in the near future. Bringing awareness and busting the myths among them is essential. This study aimed to develop a Gender Friendly Breastfeeding Knowledge scale based on a conceptual framework that reflected the knowledge of young adults and evaluates its validity and reliability. Methodology:  Development of the questionnaire for Conceptual framework and item generation was done using PubMed, Google Scholar, other sources and expert opinion. The type of measurement was structured as a 5-point Likert scale. The Lawshe technique to assess the content validity ratio. A cross-sectional survey in graduation colleges situated in Mangalagiri or within the radius of 30 km of Mangalagiri, Andhra Pradesh, India was conducted in 2020. 1400 Adult males and females aged 20-25 years and perusing full-time graduation course were recruited. For each item in the Gender Friendly Breastfeeding Awareness scale, we assessed individual item characteristics and item-test correlation. To check to construct validity, we performed exploratory factor analysis and confirmatory factor analysis. Results: Expert panel retained 23 items from initially 30 items. The content validity index score for the each of 23-items in the scale was more than 0.80. A four-factor structure perfectly fitted the data and illustrated 54 percent of the variation in knowledge of breastfeeding. Four stages of CFA were completed. The chi-square = 860.534 was significantly above the 0.01 level.  Cronbach's a = 0.787 based on standardized items reflected the overall internal consistency of the gender-friendly breastfeeding awareness scale. Conclusion: Gender-friendly breastfeeding knowledge scale is a valid and reliable tool, it is recommended that this scale be used in communities, educational institutions, and in relevant research to assess breastfeeding knowledge among young adults of both genders, thereby promoting breastfeeding practices in the future

Diarylpentanoid (1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one) (MS13) exhibits anti-proliferative, apoptosis induction and anti-migration properties on androgen-independent human prostate cancer by targeting cell cycle-apoptosis and PI3K signalling pathways

Diarylpentanoids exhibit a high degree of anti-cancer activity and stability in vitro over curcumin in prostate cancer cells. Hence, this study aims to investigate the effects of a diarylpentanoid, 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one (MS13) on cytotoxicity, anti-proliferative, apoptosis-inducing, anti-migration properties, and the underlying molecular mechanisms on treated androgen-independent prostate cancer cells, DU 145 and PC-3. A cell viability assay has shown greater cytotoxicity effects of MS13-treated DU 145 cells (EC50 7.57 ± 0.2 µM) and PC-3 cells (EC50 7.80 ± 0.7 µM) compared to curcumin (EC50: DU 145; 34.25 ± 2.7 µM and PC-3; 27.77 ± 6.4 µM). In addition, MS13 exhibited significant anti-proliferative activity against AIPC cells compared to curcumin in a dose- and time-dependent manner. Morphological observation, increased caspase-3 activity, and reduced Bcl-2 protein levels in these cells indicated that MS13 induces apoptosis in a time- and dose-dependent. Moreover, MS13 effectively inhibited the migration of DU 145 and PC-3 cells. Our results suggest that cell cycle-apoptosis and PI3K pathways were the topmost significant pathways impacted by MS13 activity. Our findings suggest that MS13 may demonstrate the anti-cancer activity by modulating DEGs associated with the cell cycle-apoptosis and PI3K pathways, thus inhibiting cell proliferation and cell migration as well as inducing apoptosis in AIPC cells

Cytotoxic, antiproliferative and apoptosis-inducing activity of L-amino acid oxidase from Malaysian Calloselasma rhodostoma on human colon cancer cells

The aim of this study was to investigate the cytotoxic, antiproliferative activity and the induction of apoptosis by L-amino acid oxidase isolated from Calloselasma rhodostoma crude venom (CR-LAAO) on human colon cancer cells. CR-LAAO was purified using three chromatographic steps: molecular exclusion using G-50 gel filtration resin, ion-exchange by MonoQ columnand desalted on a G25 column. The purity and identity of the isolated CR-LAAO was confirmed by SDS-PAGE and LC-MS/MS. CR-LAAO demonstrated time- and dose-dependent cytotoxic activity on SW480 (primary human colon cancer cells) andSW620 (metastatic human colon cancer cells) with an EC50 values of 6 lg/ml and 7 lg/ml at 48 hr, respectively. Quantification of apoptotic cells based on morphological features demonstrated significant increase in apoptotic cell population in both SW480 and SW620 cells which peaked at 48 hr. Significant increase in caspase-3 activity and reduction in Bcl-2 levels were demonstrated following CR-LAAO treatment. These data provide evidence on the potential anticancer activity of CR-LAAO from the venom of C. rhodostoma for therapeutic intervention of human colon cancer