A single-step high-throughput bioassay for quantifying Fc-containing recombinant proteins based on non-classical calculation of fluorescence polarization.

The titer of recombinant proteins is one of the key parameters in biopharmaceutical manufacturing processes. The fluorescence polarization (FP)-based assay, a homogeneous, high-throughput and real-time analytical method, had emerged as a powerful tool for biochemical analysis and environmental monitoring. In this study, an FP-based bioassay was utilized to quantify antibody fragment crystallizable (Fc)-containing proteins, such as recombinant monoclonal antibodies (mAbs) and mAb derivatives, in the cell culture supernatant, and the impacts of tracer molecular weight and FITC-coupling conditions on fluorescence polarization were methodically examined. Distinct from the fluorescence polarization potency calculated by classical formula, we for the first time proposed a new concept and calculation of fluorescence polarization intensity, based on which an analytical method with broader detection range and analysis window was established for quantifying Fc-containing proteins. This provided new ideas for the practical application of fluorescence polarization theory. The established method could detect 96 samples within 30 minutes, with dynamic titer range of 2.5-400 mg L-1, and a linear fitting R2 between the measured and actual concentration reaching 0.99. The method had great application prospects in determining the titer of recombinant proteins with Fc fragments, especially when applied to large-scale screening of high-yield and stable expression CHO cell lines commonly used in biopharmaceutical industry.

Efficacy of Computerized Tomography-Guided Core Biopsy in Identifying the Subtypes of Lung Adenocarcinoma: An Observational Perspective From Pakistan.

Background Lung carcinoma is a leading cause of death worldwide. Histological subtype of lung adenocarcinoma is an important indicator of patient's outcome as it is helpful in surgical planning and guidance of prognosis. Objective To determine the diagnostic efficacy of computerized tomography-guided core needle biopsy (CNB) in identifying the histopathological subtype of lung adenocarcinoma. Methods and materials This is a retrospective, descriptive study including clinical data of 73 patients irrespective of their age and gender, who underwent computerized tomography-guided CNB for lung masses at the Department of Pathology, Aznostics - the Diagnostic Centre, Lahore, Pakistan from January 01, 2019 to June 30, 2023. Data collected was analyzed via Google Form (Google Inc., Mountainview, CA) and Statistical Package for Social Sciences (IBM SPSS Statistics for Windows, Version 24, released 2016; IBM Corp., Armonk, New York, United States) and was sent to statistician for descriptive analysis. Categorical data was used for calculating frequency and percentage, while continuous data was computed as mean and standard deviation. Results Seventy-three patients with adenocarcinoma underwent pulmonary biopsy. The mean age of included patients was 64.88 ± 11.39 year with a male predominance of 61.64%. Upper lobe was commonly affected by adenocarcinoma lung in 57.53% patients and 58.90% cases involved the right lung. The most common subtype was acinar with 51.65% followed by solid with 17.58% cases. Computerized tomography-guided CNB showed a diagnostic yield of 75.34% and identified histological subtypes of lung adenocarcinoma in 55 cases. Conclusion Computerized tomography-guided CNB is a useful, yet minimally invasive diagnostic tool to identify the histological subtype of lung adenocarcinoma. It not only helps in planning the surgical and adjuvant management of the patients, but also guides the patient-prognosis.

A review of vaginal hysterectomies in the gynaecology department of a tertiary care hospital.

This retrospective cohort study analysed the trends and complications of vaginal hysterectomy conducted at Services Hospital, Lahore, from January 1, 2015 to December 31, 2020. Demographics, indications, surgery duration, complications (haemorrhage, urological or rectal problems, infection), and hospital stay were recorded. Out of 819 hysterectomies performed for benign gynaecological conditions, 112 (13.68%) were vaginal hysterectomies. Non-descent vaginal hysterectomy (NDVH) accounted for 33(29.46%) and uterine prolapse for 79(70.53%) of the cases. Mean age was 52.35±8.74 years, parity was 5.01±1.32, intraoperative haemorrhage was 796.87±450.1 ml, surgery duration was 48.61±12.28 minutes, and hospital stay was 2.58±0.41 days. Complications occurred in 19(16.97%) of the cases, while 93(83.03%) cases had no complications. Outcomes were comparable between NDVH and vaginal hysterectomy for prolapse (p=0.552). This indicates that vaginal hysterectomy is a safe procedure with minimal complications and quick recovery for uterine prolapse and non-descent uterus. However, a declining trend was observed over the study period.

Hispidulin: a promising anticancer agent and mechanistic breakthrough for targeted cancer therapy.

Cancer is a complex disease characterized by dysregulated cell growth and division, posing significant challenges for effective treatment. Hispidulin, a flavonoid compound, has shown promising biological effects, particularly in the field of anticancer research. The main objective of this study is to investigate the anticancer properties of hispidulin and gain insight into its mechanistic targets in cancer cells. A comprehensive literature review was conducted to collect data on the anticancer effects of hispidulin. In vitro and in vivo studies were analyzed to identify the molecular targets and underlying mechanisms through which hispidulin exerts its anticancer activities. Hispidulin has shown significant effects on various aspects of cancer, including cell growth, proliferation, cell cycle regulation, angiogenesis, metastasis, and apoptosis. It has been observed to target both extrinsic and intrinsic apoptotic pathways, regulate cell cycle arrest, and modulate cancer progression pathways. The existing literature highlights the potential of hispidulin as a potent anticancer agent. Hispidulin exhibits promising potential as a therapeutic agent for cancer treatment. Its ability to induce apoptosis and modulate key molecular targets involved in cancer progression makes it a valuable candidate for further investigation. Additional pharmacological studies are needed to fully understand the specific targets and signaling pathways influenced by hispidulin in different types of cancer. Further research will contribute to the successful translation of hispidulin into clinical settings, allowing its utilization in conventional and advanced cancer therapies with improved therapeutic outcomes and reduced side effects.

Real world data on outcomes of anti-CD38 antibody treated, including triple class refractory, patients with multiple myeloma: a multi-institutional report from the Canadian Myeloma Research Group (CMRG) Database.

Multiple myeloma (MM) remains incurable despite the availability of novel agents. This multi-center retrospective cohort study used the Canadian Myeloma Research Group Database to describe real-world outcomes of patients withanti-CD38 monoclonal antibody (mAb) refractory MM subsequently treated with standard of care (SoC) regimens. Patients with triple class refractory (TCR) disease (refractory to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 mAb) were examined as a distinct cohort. Overall, 663 patients had disease progression on anti-CD38 mAb therapy, 466 received further treatment (346 with SoC regimens were included, 120 with investigational agents on clinical trial and were excluded). The median age at initiation of subsequent SoC therapy of 67.9 (range 39.6-89.6) years with a median of 3 prior lines (range 1-9). The median PFS and OS from the start of subsequent therapy was 4.6 (95% CI 4.1-5.6) months and 13.3 (95% CI 10.6-16.6) months, respectively. The median PFS and OS of patients with TCR disease (n = 199) was 4.4 (95% CI 3.6-5.3) months and 10.5 (95% CI 8.5-13.8) months. Our results reinforce that real-world patients with relapsed MM, particularly those with TCR disease, have dismal outcomes. There remains an urgent unmet need for the development of and access to effective therapeutics for these patients.

Combined Multivariate Statistical Techniques and Water Quality Index (WQI) to Evaluate Spatial Variation in Water Quality.

In present study, Water Quality Index (WQI) has been assessed of the Rawal Lake which is a major source of drinking water for people in the Federal Capital, Islamabad, and its adjacent city Rawalpindi in Pakistan. For this, the principal component analysis (PCA) and WQI were applied as an integrated approach to quantitatively explore difference based on spatial variation in 11 water quality parameters of the five major feeding tributaries of the Rawal Lake, Pakistan. The results of temperature in water, total dissolved solids, pH, electrical conductivity, chlorides and sulfates were well within the allowable World Health Organisation's (WHO) limits. However, the heavy metals like cadmium and lead were above permissible limits by the WHO in tributaries of Bari Imam and Rumli. Moreover, this has been proven by the Pearson correlation which suggested strong positive correlation (0.910*) between lead and cadmium. The results of present study were subjected to statistical analysis, i.e., PCA which gave three major factors contributing 96.5% of the total variance. For factor 1, pH, TDS, alkalinity, chlorides, sulfates and zinc have highest factor loading values (>0.60) and presented that these parameters were among the most significant parameters of first factor. As per the WQI results, the water was categorised in two major classes indicating that water of Bari Imam and Rumli is highly contaminated with heavy metals and totally unsuitable for drinking purposes. Based on the results of the present study, it is suggested to make heavy metals consideration as an integrated component in future planning for maintaining water quality of the Rawal Lake and its tributaries.

Tamoxifen-Loaded Eudragit Nanoparticles: Quality by Design Approach for Optimization of Nanoparticles as Delivery System.

Nanoparticles have numerous applications as drug carriers in drug delivery. The aim of the study was to produce tamoxifen nanoparticles with a defined size and higher encapsulation for efficient tissue uptake with controlled drug release. The quality by design approach was utilized to produce tamoxifen-loaded Eudragit nanoparticles by identifying the significant process variables using the nanoprecipitation method. The process variables (amount of drug, polymer, and surfactant) were altered to analyze the influence on particle size (PS), % encapsulation efficiency (EE). The results showed that the drug and polymer individually as well as collectively have an impact on PS, while the surfactant has no impact on the PS. The %EE was influenced by the surfactant individually and in interaction with the drug. The linear regression model was endorsed to fit the data showing high R2 values (PS, 0.9146, %EE, 0.9070) and low p values (PS, 0.0004, EE, 0.0005). The PS and EE were confirmed to be 178 nm and 90%, respectively. The nanoparticles were of spherical shape, as confirmed by SEM and TEM. The FTIR confirmed the absence of any incompatibility among the ingredients. The TGA confirmed that the NPs were thermally stable. The in vitro release predicted that the drug release followed Higuchi model.

Transdermal Delivery of Glimepiride: A Novel Approach Using Nanomicelle-Embedded Microneedles.

Glimepiride (GM) is a hydrophobic drug that dissolves slowly and yields inconsistent clinical responses after oral administration. Transdermal drug delivery (TDD) is an appropriate alternative to oral administration. Microneedles (MNs) offer a promising delivery system that penetrates the skin, while polymeric micelles can enhance the solubility; hence, the combination of both results in high drug bioavailability. This study aims to improve glimepiride's solubility, dissolution rate, and bioavailability by incorporating nanomicelles into MNs for TDD. The nanomicelles formulated with 10% Soluplus® (SP) and 40% GM had a mean particle size of 82.6 ± 0.54, PDI of 0.1 ± 0.01, -16.2 ± 0.18 zeta potential, and achieved a 250-fold increase in solubility. The fabricated pyramid shaped GM-dissolving MNs were thermally stable and had no formulation incompatibility, as confirmed by thermal and FTIR analysis. The in vitro dissolution profile revealed that the GM release from nanomicelles and nanomicelle-loaded DMN was concentration-independent following non-Fickian transport mechanism. Improved pharmacokinetic parameters were obtained with dose of 240 µg as compared to 1 mg of GM oral tablet, in healthy human volunteers. The observed Cmax, Tmax and MRT were 1.56 µg/mL ± 0.06, 4 h, and 40.04 h ± 3.37, respectively. The safety profile assessment indicated that microneedles are safe with no adverse effects on skin or health. This study provides an alternative delivery system for the administration of glimepiride, resulting in improved bioavailability, enhanced patient compliance, and reduced dosing frequency.

The Efficacy of Metformin and Exenatide in Polycystic Ovary Syndrome (PCOS) Patients / La eficacia de metformina y exenatida en pacientes con síndrome de ovario poliquístico (SOP)

Introducción: El Síndrome del Ovario Poliquístico (SOP) es un trastorno hormonal que afecta al 5-10% de las mujeres que se encuentran en edad reproductiva. este metanálisis tiene como objetivo evaluar la eficacia de la metformina y la exenatida, respectivamente, y comparar la eficacia de ambos fármacos utilizando el Índice de Masa Corporal (IMC), el colesterol de lipoproteínas de baja densidad (LDL-C), el colesterol de lipoproteínas de alta densidad (HDL-C) y los niveles de testosterona. Método: En este estudio se consultaron Scopus, Science Direct, Oxford Journal, Wiley Online Library y Medline a través del motor de búsqueda PubMed. El análisis estadístico de los estudios incluidos se realizó mediante el software RevMan 5.4. Resultados: Hubo 6 estudios incluidos en el análisis del estudio. Hubo una reducción significativa en el IMC de las pacientes con SOP con exenatida frente a metformina (diferencia de medias = 0,51; intervalo de confianza (IC) del 95 % = 0,07; 0,96; I 2 = 52 %; p = 0,02). También hubo una reducción significativa en el nivel de testosterona de los pacientes con SOP con exenatida frente a metformina (diferencia de medias = 0,15; intervalo de confianza (IC) del 95 % = 0,07; 0,22;I 2 = 0 %; p = 0,0002). No hubo efecto sobre la media de LDL-C y de HDL-C cuando se comparó entre metformina y exenatida. Este muestra que la exenatida es eficaz para reducir el IMC y los niveles de testosterona en pacientes con SOP. Conclusiones: Hubo una reducción significativa en el IMC y los niveles de testosterona de los pacientes con SOP cuando se usó exenatida en comparación con metformina. Sin embargo, no hubo efecto sobre la media de los niveles de LDL-C y HDL-C de las pacientes con SOP. (AU)

Introduction: Polycystic Ovary Syndrome (PCOS) is a hormonal disorder that affects 5-10% of women who are their reproductive age. This meta-analysis aims to evaluate the efficacy of metformin and exenatide, respectively, and to compare the efficacy of both drugs using Body Mass Index (BMI), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and testosterone level. Method: Scopus, Science Direct, Oxford Journal, Wiley Online Library, and Medline (through the PubMed search engine) were used in this study. Statistical analysis of the included studies was done using the RevMan 5.4 software. Results: There were 6 studies included in the analysis of the study. There was a significant reduction in BMI of PCOS patients with exenatide versus metformin (mean difference = 0.51; 95% confidence interval (CI)= 0.07, 0.96, I 2= 52%; p=0.02). There was also a significant reduction in the testosterone level of PCOS patients with exenatide versus met-formin (mean difference = 0.15; 95% confidence interval (CI)= 0.07, 0.22, I 2= 0%; p=0.0002). There was no effect on the mean of LDL-C and of HDL-C when compared between metformin and exenatide This meta-analysis shows that exenatide is effective in reducing BMI and testosterone levels in PCOS patients. Conclusions: There were a significant reduction in BMI and testosterone levels of PCOS patients when exenatide was used as compared to metformin. However, there was no effect on the mean of the LDL-C and HDL-C levels of the PCOS patients. (AU)

Hybrid Dissolving Microneedle-Mediated Delivery of Ibuprofen: Solubilization, Fabrication, and Characterization.

Microneedles have recently emerged as a promising platform for delivering therapeutic agents by disrupting the skin, resulting in improved and high drug delivery via this route. Ibuprofen is widely used topically and orally for chronic pain conditions; to avoid untoward gastric effects, topical application is preferred over the oral route. This study aimed to enhance the solubility of the poorly water-soluble ibuprofen using Soluplus (SP) as a solubilizer and to fabricate dissolving microneedle patches of the drug. The fabricated patches were compared with marketed oral and topical formulations of ibuprofen. A 432-fold increase was observed in the solubility of the drug at 8% SP. The FTIR studies revealed that the drug and polymers were compatible. MNs were of uniform morphology and released the drug in a predictable manner. The in vivo analysis on healthy human volunteers revealed a Cmax of 28.7 µg/mL ± 0.5 with a Tmax of 24 h and a MRT of 19.5 h, which was significantly higher than that observed for commercially available topical formulations. The prepared ibuprofen microneedles have higher bioavailability and MRT at a lower dose (165 µg) as compared to tablet and cream doses (200 mg).

Clinical Findings and Radiological Evaluation of WHO-Defined Severe Pneumonia Among Hospitalized Children.

BACKGROUND: The leading infectious cause of death in children worldwide is pneumonia. Pneumonia claimed the lives of 740,180 kids under the age of five in 2019, accounting for 14% of all fatalities and 22% of deaths in kids between the ages of 1 and 5. Children and families worldwide are affected by pneumonia, but South Asia and Africa have the highest fatality rates. OBJECTIVE: This study aims to determine the clinical risk factors and radiological assessment of the World Health Organization (WHO)-defined severe pneumonia in Pakistani hospitalized children. MATERIAL AND METHODS: This cross-sectional study was carried out in the pediatric department of the Hayatabad Medical Complex between January 2021 and December 2021. The study included kids who had a fever, cough, and fast or difficulty breathing between the ages of 2 and 60 months. All of the included clinical pneumonia cases were acquired in the community. RESULTS: A total of 360 clinically confirmed patients with pneumonia who presented with fever, cough, and fast or difficulty breathing were enrolled. Age ranged between 2 and 60 months, with a mean age of ±31 months. There were 168 (46.7%) males and 192 (53.3%) females. About 232 (64.4%) had radiological pneumonia, while the rest of the pneumonia cases 128 (35.5%) were without a radiological diagnosis. The most common presenting complaint was noisy breathing 119 (33%), followed by refusal of feeds 81 (22.5%), lethargy 69 (19.2%), seizure 40 (11.1%), nasal drainage 29 (8%), and abdominal pain 22 (6.1%). CONCLUSION: The most specific clinical finding of radiographic pneumonia was bronchial breathing, while tachypnea was the most sensitive sign.

Structural and functional insight into thiazolidinone derivatives as novel candidates for anticancer drug design: in vitro biological and in-silico strategies.

The compounds 2a-2h containing a thiazolidinone pharmacophore were synthesized via hetrerocylization of thiosemicarbazones with dimethyl acetylenedicarboxylate. The hybrid molecules were evaluated for anticancer activity against the human cell lines MCF-7, T47D (human breast adenocarcinoma) and HeLa (cervical cancer). Compounds 2c showed effective cytotoxicity on MCF-7 and HeLa (GI50 6.40 ± 0.10 µM/mL and GI5010.30 ± 1.09 µM/mL), and compound 2d also showed effective cytotoxicity against MCF-7 and HeLa cell lines i.e., (GI50 16.60 ± 0.21 µM/mL and GI50 15.02 ± 0.14 µM/mL). These findings were comparable to cisplatin (azane;dichloroplatinum) the standard drug (GI50 13.20 ± µM/mL and 15.10 µM/mL respectively) and consequently nominated for determination of the mode of cell death. The results revealed the cytotoxic effects of 2c and 2d by induction of apoptosis in MCF-7 and HeLa cell lines. Moreover the results were further supported by the Molecular Docking which predicts the binding interactions of the best anticancer ligands with Ribonucleotide reductase (RNR), which is essential enzyme required for de-novo synthesis of DNA precursors. Molecular dynamic simulations were also performed to determine the stability of protein-ligand complex under different simulated conditions. In addition, the computational studies including DFTs, ADMET properties suggested these compounds can act as lead molecules, for the synthesis of novel drug candidates for the treatment of specific cancer and its associated malignancies.

Cancer and Disease Diagnosis - Biosensor as Potential Diagnostic Tool for Biomarker Detection.

Analysis of cancer biomarkers has enormous promise for advancing our molecular understanding of illness and facilitating more precise and timely diagnosis and follow-up care. MicroRNA, exosomes, ctDNA, CTCs, and proteins are only some of the circulating biomarkers that can be detected by liquid biopsy instead of the more intrusive and time-consuming process of doing a tissue biopsy. As the cancer diagnosis bio-markers reveal ultra-low levels in the early stages of the disease, highly sensitive approaches are urgently required. Researchers have taken an interest in a optical biosensor for detecting cancer biomarkers as a potential tool for early disease diagnosis. These techniques have the potential to aid in the development of effective treatments, ultimately leading to a higher rate of patient survival. This review briefly discuss the i) understanding of cancer and biomarkers for early diagonosis purpose ii) Molecular methods and ii) biosensor-based diagnostics. The reseach primary focus on advancement in biosensor design using various concepts ie., Electrochemical, Chemiluminescence and Colorimetric, Surface plasmons (SP), Surface plasmon resonance (SPR), localized surface plasmon resonance (LSPR), Fluorescence, Fiber-based sensors, Terahertz based biosensors, and Surface enhanced Raman spectroscopy (SERS). As a result of the local electric field amplification around plasmonic (usually gold and silver) nanostructures, surface-enhanced Raman spectroscopy (SERS) has emerged as a rapid, selective, and sensitive alternative to conventional laboratory analytical methods, making significant strides in a number of biosensing applications but still under developing stage to be used as diagnostic tool in clinical research.

Cancer and Apoptosis.

Cancer is an uncontrolled growth of normal cells due to unchecked regulatory mechanisms working inside the rapidly dividing cells. In this complex cancer disease treatment, various strategies are utilized to get rid of cancer cells effectively. The different methods combine approaches used to treat cancer, such as radiotherapy, surgery, and chemotherapy. Chemotherapy is among the most effective ways, along with radiotherapy and surgical removal of cancer tissue. Effective chemotherapy based on modification of conventional drugs along with various molecular therapeutic targets, which involve different inhibitors that work in a specific manner in inhibiting particular events activated in cancer cells-the understanding of molecular signaling pathways holds key in the development of targeted therapeutics. After the fundamental signaling pathway studies, a single signaling pathway targeting approach or multiple targeting could display remarkable results in cancer therapeutics. The signal approach includes the signal pathway target. However, a double targeted pathway could effectively aid in inhibiting cell growth or metastasis either due to triggering natural suicidal mechanism (apoptosis) activation. The particular environment of cells regulates cell growth and differentiation. Various proteins in the extracellular matrix (ECM) regulate the process of cancer initiation or progression. The ECM collagens, elastins proteins, fibronectins, and laminins might reduce the effectiveness of treatment therapy, reflecting them as an essential target. Any dysregulation in the composition of ECM reflects the regulatory ineffectiveness in a particular area. These have an association with poor prognosis, cell propagation, and metastasis, along drug resistance.Regulation in physiological processes associated with developmental process and maintaining the homeostasis. The pathogenesis of cancer might be connected to dysregulation in cell death programs, including autophagy, necrosis, and the most desirable cell death mechanism called apoptosis: programmed cell death, the highly regulatory mechanism of natural cell death involved in tissue development. The apoptosis involves characteristic feather of cell death which includes specific morphological change along with biochemical alteration. It includes tightly regulated irreversible events, i.e., phosphatidylserine externalization and DNA fragmentation, mainly via the intrinsic and extrinsic pathways. Targeting apoptosis in the development of therapeutics could be the ultimate process in treating cancer via chemotherapy. During apoptosis, cell death occurs without causing much damage or inflammation in neighboring cells. Various pro-apoptosis and anti-apoptosis proteins involved in the regulation of apoptosis could act as a remarkable target. The apoptosis inactivation is the critical dysregulatory process in the majority of cancer types. There is an increase in research development regarding apoptosis-targeted therapeutics. A understanding of apoptotic signaling pathways, a fundamental knowledge, aids in developing particular inhibitors for anti-apoptotic and activator of pro-apoptotic proteins.In both apoptosis pathways (extrinsic and intrinsic), pro-apoptotic and anti-apoptotic proteins act as potential regulators in cell division and growth. The pro-apoptotic proteins Bax trigger the activation of the intrinsic pathway, an excellent target for developing therapeutics, and are currently in clinical trials. Similarly, the inhibitor of the anti-apoptotic proteins is also on track in the drug development process. The considerable importance of apoptosis-based anticancer drugs is also due to improving the drug sensitivity via reversing the resistive mechanisms in cancer cells. The dysregulatory or inactivated apoptosis mechanism involve Bcl-2 family proteins which include both pro-apoptotic members downregulation and anti-apoptotic upregulation, various inhibitors of apoptosis as inhibitory proteins (IAPs), cell cycle dysregulation, dysregulatory repair system, cell progression pathway activation of NF-κB, tumor suppressor (p53) regulation, and death receptors (DRs) of the extrinsic pathway.

Cancer and apoptosis: The apoptotic activity of plant and marine natural products and their potential as targeted cancer therapeutics.

Cancer is a multifactorial, multi-stage disease, including complex cascades of signaling pathways-the cell growth governed by dysregulated and abrupt cell division. Due to the complexity and multi-regulatory cancer progression, cancer is still a challenging disease to treat and survive. The screening of extracts and fractions from plants and marine species might lead to the discovery of more effective compounds for cancer therapeutics. The isolated compounds and reformed analogs were known as future prospective contenders for anti-cancer chemotherapy. For example, Taxol, a potent mitotic inhibitor discovered from Taxus brevifolia, suppresses cell growth and arrest, induces apoptosis, and inhibits proliferation. Similarly, marine sponges show remarkable tumor chemo preventive and chemotherapeutic potential. However, there is limited research to date. Several plants and marine-derived anti-cancer compounds having the property to induce apoptosis have been approved for clinical trials. The anti-cancer activity kills the cell and slows the growth of cancer cells. Among cell death mechanisms, apoptosis induction is a more profound mechanism of cell death triggered by naturally isolated anti-cancer agents. Evading apoptosis is the major hurdle in killing cancer cells, a mechanism mainly regulated as intrinsic and extrinsic. However, it is possible to modify the apoptosis-resistant phenotype of the cell by altering many of these mechanisms. Various extracts and fractions successfully induce apoptosis, cell-cycle modulation, apoptosis, and anti-proliferative activity. Therefore, there is a pressing need to develop new anti-cancer drugs of natural origins to reduce the effects on normal cells. Here, we've emphasized the most critical elements: i) A better understanding of cancer progression and development and its origins, ii) Molecular strategies to inhibit the cell proliferation/Carcino-genesis, iii) Critical regulators of cancer cell proliferation and development, iv) Signaling Pathways in Apoptosis: Potential Targets for targeted therapeutics, v) Why Apoptosis induction is mandatory for effective chemotherapy, vi) Plants extracts/fractions as potential apoptotic inducers, vii) Marine extracts as Apoptotic inducers, viii) Marine isolated Targeted compounds as Apoptotic inducers (FDA Approved/treatment Phase). This study provides a potential therapeutic option for cancer, although more clinical studies are needed to verify its efficacy in cancer chemotherapy.

How stereotype threat affects the brain dynamics of creative thinking in female students.

When people are placed in a situation where they are at risk of substantiating a negative stereotype about their social group (a scenario termed stereotype threat), the extra pressure to avoid this outcome can undermine their performance. Substantial and consistent gender disparities in STEM fields leave women vulnerable to stereotype threat, including the stereotype that women are not as good at generating creative and innovative ideas as men. We tested whether female students' creative thinking is affected by a stereotype threat by measuring power in the alpha frequency band (8-12Hz oscillations) that has been associated with better creative thinking outcomes. Counter to expectations that a stereotype threat would reduce alpha power associated with creative thinking, analyses showed increased alpha power following the introduction of the stereotype threat. This outcome suggests that women may have attempted to increase their internal attention during the task in order to disprove the stereotype. Behaviorally, this effort did not lead to changes in creative performance, suggesting that the stereotype threat decoupled alpha power from creative thinking outcomes. These results support a growing school of thought in the neuroscience of creativity literature that the alpha power often seen in conjunction with creative behavior is not necessarily related to the creativity processes themselves, but rather might be part of a larger network modulating the distribution of attentional resources more broadly.

Synthesis and Evaluation of 1,3,5-Triaryl-2-Pyrazoline Derivatives as Potent Dual Inhibitors of Urease and α-Glucosidase Together with Their Cytotoxic, Molecular Modeling and Drug-Likeness Studies.

In the present work, a concise library of 1,3,5-triaryl-2-pyrazolines (2a-2q) was designed and synthesized by employing a multistep strategy, and the newly synthesized compounds were screened for their urease and α-glucosidase inhibitory activities. The compounds (2a-2q) were characterized using a combination of several spectroscopic techniques including FT-IR, 1H NMR, 13C NMR, and EI-MS. All the synthesized compounds, except compound 2i, were potent against urease as compared to the standard inhibitor thiourea (IC50 = 21.37 ± 0.26 µM). These analogs disclosed varying degrees of urease inhibitory activities ranging from 9.13 ± 0.25 to 18.42 ± 0.42 µM. Compounds 2b, 2g, 2m, and 2q having IC50 values of 9.36 ± 0.27, 9.13 ± 0.25, 9.18 ± 0.35, and 9.35 ± 0.35 µM, respectively, showed excellent inhibitory activity as compared to standard thiourea (IC50 = 21.37 ± 0.26 µM). A kinetic study of compound 2g revealed that compound 2g inhibited urease in a competitive mode. Among the synthesized pyrazolines, the compounds 2c, 2k, 2m, and 2o exhibited excellent α-glucosidase inhibitory activity with the lowest IC50 values of 212.52 ± 1.31, 237.26 ± 1.28, 138.35 ± 1.32, and 114.57 ± 1.35 µM, respectively, as compared to the standard acarbose (IC50 = 375.82 ± 1.76 µM). The compounds (2a-2q) showed α-glucosidase IC50 values in the range of 114.57 ± 1.35 to 462.94 ± 1.23 µM. Structure-activity relationship revealed that the size and electron-donating or -withdrawing effects of substituents influenced the activities, which led to the urease and α-glucosidase inhibiting properties. Compound 2m was a dual potent inhibitor against urease and α-glucosidase due to the presence of 2-CF3 electron-withdrawing functionality on the phenyl ring. To the best of our knowledge, these synthetic compounds were found to be the most potent dual inhibitors of urease and α-glucosidase with minimum IC50 values. The cytotoxicity of the compounds (2a-2q) was also investigated against human cell lines MCF-7 and HeLa. Compound 2l showed moderate cytotoxic activity against MCF-7 and HeLa cell lines. Moreover, in silico studies on most active compounds were also performed to understand the binding interaction of most active compounds with active sites of urease and α-glucosidase enzymes. Some compounds exhibited drug-like characteristics due to their lower cytotoxic and good ADME profiles.

Effect of Cypermethrin on Blood Hematology and Biochemical Parameters in Fresh Water Fish Ctenopharyngodon idella (Grass Carp).

The insecticide, cypermethrin, adversely affects biochemical parameters in blood and behavior in grass carp (Ctenopharyngodon idella). Fish were obtained from hatchery, reared in the laboratory. Different concentration of cypermethrin were applied. Blood was collected and hematological and biochemical parameters were measured. Biochemical parameters such as, protein levels, cholesterol, phosphorous and calcium in both acute and chronically cypermethrin treated groups decreased, with increasing exposure time from 24h to 15 days with more pronounced effects in the acute groups. Increased glucose, urea, serum glutamic pyruvic transaminase (SGPT), creatinine, and lactate dehydrogenase (LDH) levels were found in both acute and chronic groups with the increasing exposure time. Hematological parameters, such as red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MHCH), and red cell distribution width (RDW) were significantly reduced in both groups as the exposure time increases. However, the numbers of white blood cells (WBC) and platelets were increased. This study established both the acute and chronic toxicity of cypermethrin in grass carp, which likely occurs secondary to altered biochemical and blood parameters.