A discovery of potent kaempferol derivatives as multi-target medicines against diabetes as well as bacterial infections: an in silico approach.

Flavonoids demonstrate beneficial effects on human health because flavonoids contain important biological properties. Kaempferol is a flavonol, type of flavonoid found in eatable plants and in plants usually employed in ancient drugs (Moringa oleifera, Tilia spp., fern genus spp. and gingko etc.). Some medicinal studies have shown that the use of foods full of kaempferol decreases the risk of many (cancer, vascular) diseases. All the data of 50 kaempferol derivatives were collected from PubChem database. Through Schrödinger software, 3D-QSAR study was performed for 50 compounds by using method of field base. Conformer of kaempferol derivatives was docked against anti-diabetic, anti-microbial co-crystal structures and protein. To monitor the best anti-diabetic and antibacterial agent, particular kaempferol derivatives were downloaded from PubChem database. Virtual screening by molecular docking provided four lead compounds with four different proteins. These hit compounds were found to be potent inhibitor for diabetic enzymes alpha-amylase and DPP IV and had the potential to suppress DNA gyrase and dihydrofolate reductase synthesis. Molecular dynamic simulation of docked complexes evaluates the value of root mean square fluctuation by iMOD server. Kaempferol 3-O-alpha-L-(2, 3-di-Z-p-coumaroyl) rhamnoside (42) compound used as anti-diabetic and kaempferol 3-O-gentiobioside (3) as antibacterial with good results can be used for drug discovery.Communicated by Ramaswamy H. Sarma.

Impact of COVID-19 pandemic on older cancer patients: Proposed solution by the International Geriatric Radiotherapy Group.

Older cancer patients are disproportionally affected by the Coronavirus 19 (COVID-19) pandemic. A higher rate of death among the elderly and the potential for long-term disability have led to fear of contracting the virus in these patients. This fear can, paradoxically, cause delay in diagnosis and treatment that may lead to a poor outcome that could have been prevented. Thus, physicians should devise a policy that both supports the needs of older patients during cancer treatment, and serves to help them overcome their fear so they seek out to cancer diagnosis and treatment early. A combination of telemedicine and a holistic approach, involving prayers for older cancer patients with a high level of spirituality, may improve vaccination rates as well as quality of life during treatment. Collaboration between health care workers, social workers, faith-based leaders, and cancer survivors may be crucial to achieve this goal. Social media may be an important component, providing a means of sending the positive message to older cancer patients that chronological age is not an impediment to treatment.

Quantitative Profiling of Alpha-Subunit of IL-3 Receptor on Single Acute Myeloid Leukemia Cells by Super-Resolution Imaging.

BACKGROUND: Quantitative profiling of specific cell surface markers is a new approach in characterization of tumor heterogeneity and single cell biology. The current tools have dearth in detection and quantification of receptor proteins on single cells. METHODS: we focused on our newly developed protocol to determine the distribution pattern and density of cell surface markers on single acute myeloid leukemia cells. Cell surface proteins were labeled with quantum dots (Qdots) followed by super resolution Structured Illumination Microscopy (SIM) imaging to imprisonment the optical signals emitted by Qdots which were further analyzed by software imaris to do three dimensional (3D) structure reconstruction and digital simulation. Furthermore, MTT assays and flow cytometry was performed to establish association between expression of cell surface markers and drug response. RESULTS: In the present study, we found that the Molm13 and cytarabine-enriched Molm13 cells exhibit different densities of CD123, an alpha-subunit of interleukin-3 receptor, i.e. 0.92 and 1.73 per µm2 of cell surface respectively. Sub-populations of Molm13 cells expressing higher densities of CD123 on cells membranes showed resistance against cytarabine. Further study revealed that romidepsin sensitized and augmented the cytotoxicity of cytarabine in Molm13 and cytarabine-enriched Molm13 cells. Romidepsin increased the percentage of cell death-induced by cytarabine from 21.6 % to 28.6 % and 37.1 % to 57.2 % in Molm13 and cytarabine-enriched Molm13 cells respectively. CONCLUSION: Altogether, the study suggests that Molm13 cells have sub-populations with differential expression of CD123+ phenotype. Romidepsin sensitizes and augments the effect of cytarabine in Molm13 and cytarabine-enriched Molm13 cells.

Characterization and anticancer potential of Withania somnifera fruit bioactives (a native species to Pakistan) using gas chromatography-mass spectrometer, nuclear magnetic resonance and liquid chromatography-mass spectrometry-electrospray ionization.

INTRODUCTION: Withania somnifera (W. somnifera) is a plant with remarkable pharmacological properties. The plant has an impressive profile of medicinal uses in the folk medicine system of several civilizations. AIM: This comprehensive study is aimed to characterize phytochemicals in fruit of W. somnifera and tested for anticancer potential to find out active candidate in disease prevention and treatment. METHODS: The bioactive components from W. somn-ifera fruit were extracted with polar and non-polar solvents. Anticancer potential of the isolated bioactive was assessed against different cancer cell lines through MTT assay and Incucytes imaging analysis. The extracts were characterized for secondary metabolites using GC-MS (gas chromatography-mass spectrometer), LCMS (liquid chromatography-mass spectrometry)-ESI (electrospray Ionization) and 1H-NMR (electrospray Ionization) techniques. RESULTS: Both freeze-dried and rotary evaporator con-densed extracts exhibited anticancer potential against MDA-MB-231, MCF7- SKOV3 and SKBR3 cell lines. The tested extracts have cell growth inhibition potential ag-ainst mammalian cancer cell line. Hexacosanedioic acid purified from -hexane extract through HPLC was inves-tigated for its cytotoxicity against breast cancer cell line SKBR3 by using Incucytes imaging analysis. CONCLUSION: We found that a variety of bioactive compounds existed in this plant. One identified compound that was not investigated for cytotoxicity in previous studies was purified and its application showed cytotoxicity on breast cancer cell lines. A number of bioactive identified from fruit may have an effective potential for development into chemotherapy drugs.

Immunotherapy and Modern Radiotherapy Technique for Older Patients with Locally Advanced Head and Neck Cancer: A Proposed Paradigm by the International Geriatric Radiotherapy Group.

The standard of care for locally advanced head and neck cancer is concurrent chemoradiation or postoperative irradiation with or without chemotherapy. Surgery may not be an option for older patients (70 years old or above) due to multiple co-morbidities and frailty. Additionally, the standard chemotherapy of cisplatin may not be ideal for those patients due to oto- and nephrotoxicity. Though carboplatin is a reasonable alternative for cisplatin in patients with a pre-existing hearing deficit or renal dysfunction, its efficacy may be inferior to cisplatin for head and neck cancer. In addition, concurrent chemoradiation is frequently associated with grade 3-4 mucositis and hematologic toxicity leading to poor tolerance among older cancer patients. Thus, a new algorithm needs to be developed to provide optimal local control while minimizing toxicity for this vulnerable group of patients. Recently, immunotherapy with check point inhibitors (CPI) has attracted much attention due to the high prevalence of program death-ligand 1 (PD-L1) in head and neck cancer. In patients with recurrent or metastatic head and neck cancer refractory to cisplatin-based chemotherapy, CPI has proven to be superior to conventional chemotherapy for salvage. Those with a high PD-L1 expression defined as 50% or above or a high tumor proportion score (TPS) may have an excellent response to CPI. This selected group of patients may be candidates for CPI combined with modern radiotherapy techniques, such as intensity-modulated image-guided radiotherapy (IM-IGRT), volumetric arc therapy (VMAT) or proton therapy if available, which allow for the sparing of critical structures, such as the salivary glands, oral cavity, cochlea, larynx and pharyngeal muscles, to improve the patients' quality of life. In addition, normal organs that are frequently sensitive to immunotherapy, such as the thyroid and lungs, are spared with modern radiotherapy techniques. In fit or carefully selected frail patients, a hypofractionated schedule may be considered to reduce the need for daily transportation. We propose a protocol combining CPI and modern radiotherapy techniques for older patients with locally advanced head and neck cancer who are not eligible for cisplatin-based chemotherapy and have a high TPS. Prospective studies should be performed to verify this hypothesis.

Chitosan Oligosaccharide Prevents Afatinib-Induced Barrier Disruption and Chloride Secretion through Modulation of AMPK, PI3K/AKT, and ERK Signaling in T84 Cells.

Diarrhea is an important adverse effect of epidermal growth factor receptor-tyrosine kinase inhibitors, especially afatinib. Novel antidiarrheal agents are needed to reduce epidermal growth factor receptor-tyrosine kinase inhibitor-associated diarrhea to improve the quality of life and treatment outcome in cancer patients. This study aimed to investigate the anti-diarrheal activity of chitosan oligosaccharide against afatinib-induced barrier disruption and chloride secretion in human intestinal epithelial cells (T84 cells). Chitosan oligosaccharide (100 µg/mL) prevented afatinib-induced barrier disruption determined by changes in transepithelial electrical resistance and FITC-dextran flux in the T84 cell monolayers. In addition, chitosan oligosaccharide prevented afatinib-induced potentiation of cAMP-induced chloride secretion measured by short-circuit current analyses in the T84 cell monolayers. Chitosan oligosaccharide induced the activation of AMPK, a positive regulator of epithelial tight junction and a negative regulator of cAMP-induced chloride secretion. Moreover, chitosan oligosaccharide partially reversed afatinib-induced AKT inhibition without affecting afatinib-induced ERK inhibition via AMPK-independent mechanisms. Collectively, this study reveals that chitosan oligosaccharide prevents the afatinib-induced diarrheal activities in T84 cells via both AMPK-dependent and AMPK-independent mechanisms. Chitosan oligosaccharide represents a promising natural polymer-derived compound for further development of treatment for afatinib-associated diarrheas.

Biodiesel Production from Alkali-Catalyzed Transesterification of Tamarindus indica Seed Oil and Optimization of Process Conditions.

Biodiesel is considered a sustainable alternative to petro-diesel owing to several favorable characteristics. However, higher production costs, primarily due to the use of costly edible oils as raw materials, are a chief impediment to its pecuniary feasibility. Exploring non-edible oils as raw material for biodiesel is an attractive strategy that would address the economic constraints associated with biodiesel production. This research aims to optimize the reaction conditions for the production of biodiesel through an alkali-catalyzed transesterification of Tamarindus indica seed oil. The Taguchi method was applied to optimize performance parameters such as alcohol-to-oil molar ratio, catalyst amount, and reaction time. The fatty acid content of both oil and biodiesel was determined using gas chromatography. The optimized conditions of alcohol-to-oil molar ratio (6:1), catalyst (1.5% w/w), and reaction time 1 h afforded biodiesel with 93.5% yield. The most considerable contribution came from the molar ratio of alcohol to oil (75.9%) followed by the amount of catalyst (20.7%). In another case, alcohol to oil molar ratio (9:1), catalyst (1.5% w/w) and reaction time 1.5 h afforded biodiesel 82.5% yield. The fuel properties of Tamarindus indica methyl esters produced under ideal conditions were within ASTM D6751 biodiesel specified limits. Findings of the study indicate that Tamarindus indica may be chosen as a prospective and viable option for large-scale production of biodiesel, making it a substitute for petro-diesel.

Deoxyelephantopin and Its Isomer Isodeoxyelephantopin: Anti-Cancer Natural Products with Multiple Modes of Action.

Cancer is a leading cause of morbidity and mortality worldwide. The development of cancer involves aberrations in multiple pathways, representing promising targets for anti-cancer drug discovery. Natural products are regarded as a rich source for developing anti-cancer therapies due to their unique structures and favorable pharmacology and toxicology profiles. Deoxyelephantopin and isodeoxyelephantopin, sesquiterpene lactone compounds, are major components of Elephantopus scaber and Elephantopus carolinianus, which have long been used as traditional medicines to treat multiple ailments, including liver diseases, diabetes, bronchitis, fever, diarrhea, dysentery, cancer, renal disorders, and inflammation-associated diseases. Recently, deoxyelephantopin and isodeoxyelephantopin have been extensively explored for their anti-cancer activities. This review summarizes and discusses the anti-cancer activities of deoxyelephantopin and isodeoxyelephantopin, with an emphasis on their modes of action and molecular targets. Both compounds disrupt several processes involved in cancer progression by targeting multiple signaling pathways deregulated in cancers, including cell cycle and proliferation, cell survival, autophagy, and invasion pathways. Future directions of research on these two compounds towards anti-cancer drug development are discussed.

Therapeutic potential and bioactive phenolics of locally grown Pakistani and Chinese varieties of ginger in relation to extraction solvents

Abstract Current study compares the Therapeutic/nutra-pharmaceuticals potential and phenolics profile of Pakistani grown Pakistani and Chinese varieties of ginger. Crude yield of bioactive components from the varieties tested, using different extraction solvents including chloroform, ethyl acetate, ether, methanol, ethanol and distilled water. The crude bioactives varied from 14.1-82.5%. The highest extraction yield was noted for Pakistani species. The HPLC analysis revalued significant amounts of phenolics including vanillin, protocatechuic, vanillic, ferulic, sinapinic and cinnamic acids. The highest anti-inflammatory activity was shown by ethanolic extract of Pakistani variety (IC50: 26.5±1.8) whereas Chinese variety exhibited potent anticancer potential against MCF-7 cell line (Inhibition: 91.38 %). The Chinese variety in general showed higher phenolics and anticancer, while the Pakistani exhibited higher anti-inflammatory activity. Pakistani grown ginger and ethanolic extract of Chinese ginger showed highest antimicrobial activity against Pseudomonas aeruginosa 18.0±0.02 & 15.00±0.02 mm respectively. Minimum results obtained with water for both varieties of ginger with range of 7.2±0.22 and 6±0.07 respectively. Moreover, the phenolics composition, anti-inflammatory, antibacterial and anticancer activities of both tested varieties of ginger were notably affected as a function of extraction solvents. Our findings advocate selection of appropriate solvent for recovery of effective phenolic bioactive compounds from ginger verities to support the Nutra-pharmaceutical formulation.

GC-MS Metabolomics profiling and HR-APCI-MS characterization of potential anticancer compounds and antimicrobial activities of extracts from Picrorhiza kurroa roots.

The present study explores pharmacological potential and phytochemicals profiling of Picrorhiza kurroa extracts against mammalian cancer cell lines and pathogenic microbes. Bioactive extracts from roots of Picrorhiza kurroa were recovered in the methanol, 50% aqueous dichloromethane (50 : 50 v/v) and n-hexane. Antimicrobial activity of the bioactive extracts was assessed against selected strains of bacteria and pathogenic fungi. Aqueous dichloromethane extract showed highest zone of growth inhibition (39.06 ± 1.0 mm) towards Staphylococcus aureus bacteria while methanolic extract showed the lowest inhibition (6.3 ± 4.1 mm) to Escherichia coli bacteria. The tested extracts such as methanol and aqueous dichloromethane exhibited higher inhibition antifungal activity against Aspergillus flavus compared to Fusarium oxysporum. As far as cytotoxicity (MTT assay) of the tested extracts is concerned, n-hexane and aqueous dichloromethane extracts were found to be very active against all cancer cell lines (breast cancer MCF7, MDA-MB-231, SKBR3 and ovarian cancer SKOV3). A preliminary phytochemicals profiling was performed in extracts using GC-MS. Several fractions of active extract were separated with HPLC and analyzed using High Resolution Atmospheric Pressure Chemical Ionization Mass Spectrometry (HR-APCI-MS). Two purified compounds (Dihydromikanolide and 1,3-Dicyclohexyl-4-(cyclohexylimino)-2-(cyclohexylethylamino)-3,4-dihydro-1,3-diazetium) were further evaluated for their anticancer activity against ovarian cancer cell line. Our findings depict that all the tested extracts showed considerable anticancer potential through cell viability assays. The purified compound 1 - Dihydromikanolide from methanolic extract was found to be active against ovarian cancer cells and can be explored as a promising nutra-pharmaceutical candidate against ovarian cancer. However, further studies exploring the molecular pathways and in vivo testing are required.

Phytochemical investigation and effective therapeutic potential of plants extracts against breast and ovarian cancer cell lines: compounds from zizyphus mauritiana and triticum aestivum.

ancer is the leading cause of death, accounting for approximately one out of six people dying with this disease worldwide. Among all, the breast and ovarian cancers are top-ranked causes of women mortalities compared to other disorders. Although, there is advancement in technologies, but still, there are unresolved concerns to overcome the global disease burden. Currently, plants are being explored as a natural remedy to cure disorders. This research was planned to explore phytochemicals in methanolic extracts of Zizyphus mauritiana and Triticum aestivum, and their pharmacological activities were studied through Agrobacterium tumefaciens bacteria, in vitro breast cancer cell line and ovarian cancer cell line to find out novel candidates in disease control and prevention. Eleven different types of bioactive compounds were analysed in the tested extracts. The highest crude extracts percentage (75±0.02) was observed with Z. mauritiana. The extracts showed promising cell growth inhibition and tumor initiation inhibition in potato disc assay. MTT assay and Incucytes imaging analysis revealed that Z. mauritiana extract had a higher anticancer potential with 40 ± 0.92 cell viability against breast cancer cells (SKBR3) and 45 ±0.29 against ovarian cancer cells (SKOV3). In conclusion, these extracts could be used as chemotherapeutics owing to their cheapness, and easy availability. While detailed study is required for further purification and characterization of bioactives/target compounds and in-vivo activity confirmations.

Using least angular regression to model the antibacterial potential of metronidazole complexes.

Imidazole has anti-inflammatory, antituberculotic, antimicrobial, antimycotic, antiviral, and antitumor properties in the human body, to name a few. Metronidazole [1-(2-Hydroxyethyl)-2-methyl-5-nitroimidazole] is a widely used antiprotozoan and antibacterial medication. Using fourier transform infrared spectroscopy, the current study models the antibacterial activity of already synthesised Metronidazole (MTZ) complexes ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text]) against E. coli, B. bronceptica, S. epidermidis, B. pumilus and S. aureus. To characterise the Metronidazole complexes for antibacterial activity against 05 microbes, the least angular regression and least absolute shrinkage selection operators were used. Asymmetric Least Squares was used to correct the spectrum baseline. Least angular regression outperforms cross-validated root mean square error in the fitted models. Using Least angular regression, influential wavelengths that explain the variation in antibacterial activity of Metronidazole complexes were identified and mapped against functional groups.

Soft threshold partial least squares predicts the survival fraction of malignant glioma cells against different concentrations of methotrexate's derivatives.

Chemotherapy appeared to be a significant advancement in cancer research, with fewer side effects. Methotrexate (MTX) is a widely used anticancer drug with strong activity but serious side effects. Several MTX derivatives have been reported, with modifications at various sites to reduce side effects and increase efficacy. The current study uses FTIR spectroscopy to predict the survival fraction of human malignant glioma U87 (MG-U87) cell lines against MTX derivatives. Together with Parent MTX several aldehydes viz. Benzaldehyde, Chlorobenzaldehyde, 2-Chlorobenzaldehyde, 3-Nitrobenzaldehyde, 5-Chloro-2-hydroxybenz-aldehyde, 2-Hydroxy-5-Nitrobenzaldehyde, 2-Thiocarboxyaldehyde, Trans-2-pentenal, and Glutaraldehyde are treated with MTX to obtain MTX derivatives. The prediction of survival fraction of malignant glioma cells is carried out by Lasso, Elastic net and Soft PLS at different concentration levels of synthesized derivatives, including 400 µM, 200 µM, 100 µM, 50 µM, 25 µM and 12.5 µM. The cross-validated prediction error is minimised to optimise spectral wavelength selection and model parameters. It appears that the RMSE computed from test data is significantly varying with the change of models (p = 0.012), with the change of concentrations levels (p [Formula: see text]) and with the change of combination of models and concentration level (p [Formula: see text]). StPLS outperforms in predicting survival fraction of glioma cells at the concentration level 50 µM, 100 µM and 400 µM respectively with relative RMSE = 0.1,0.14 and 0.55. Lasso outperforms at the concentration level 12.5 µM, and 200 µM respectively with relative RMSE = 0.4 and 0.14. Elastic net outperforms at the concentration level 25 µM with relative RMSE = 0.8. Consistently appeared influential wavelength identifies the influential functional compounds which best predicts the survival fraction. Hence FTIR appears potential candidate for estimating survival fraction of MTX derivatives.

Structure-Based Designing, Solvent Less Synthesis of 1,2,3,4-Tetrahydropyrimidine-5-carboxylate Derivatives: A Combined In Vitro and In Silico Screening Approach.

OBJECTIVE: In this study, small molecules possessing tetrahydropyrimidine derivatives have been synthesized having halogenated benzyl derivatives and carboxylate linkage. As previously reported, FDA approved halogenated pyrimidine derivatives prompted us to synthesize novel compounds in order to evaluate their biological potential. METHODOLOGY: Eight pyrimidine derivatives have been synthesized from ethyl acetoacetate, secondary amine, aromatic benzaldehyde by adding catalytic amount of CuCl2·2H2O via solvent less Grindstone multicomponent reagent method. Molecular structure reactivity and virtual screening were performed to check their biological efficacy as an anti-oxidant, anti-cancer and anti-diabetic agent. These studies were supported by in vitro analysis and QSAR studies. RESULTS: After combined experimental and virtual screening 5c, 5g and 5e could serve as lead compounds, having low IC50 and high binding affinity.

Synthesis, Characterization and Anti-Cancer Therapeutic Potential of Withanolide-A with 20nm sAuNPs Conjugates Against SKBR3 Breast Cancer Cell Line.

BACKGROUND: Nanotechnology is gaining emerging interest in advanced drug discovery therapeutics due to their tremendous properties including enhanced delivery of therapeutic payload, extensive surface to volume ratio, high permeability, retention behaviors, etc. The gold nanoparticles (AuNPs) are favored due to their advanced features, such as biogenic, tunable physiochemical response, ease in synthesis, and wide range of biomedical applications. The phytochemicals have been focused to design Au nano-carrier-based conjugation for active-targeting drug delivery due to their nano conjugation ability. AIM: The present study describes the facile synthesis of 20nm spherical AuNPs and their conjugation with reported anti-cancer phytocompound Withanolide-A (1). METHODS: The 20nm sAuNPs were synthesized chemically and characterized their phytochemical gold nanoconjugates through UV-visible spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM) imaging techniques. The anti-cancer therapeutic potentials were tested with both nanoconjugates and pure WithanolideA (1) by using SKBR3 breast cancer cells line. RESULTS: The synthesized sAuNPs showed significant conjugation with Withanolide-A and showed stability. Furthermore, these Au nanoconjugates with Withanolide-A (1) significantly induce blockage of SKBR3 cell growth at half maximal active concentration that compared to pure Withanolide-A (1). CONCLUSION: Our findings provide a foundation to further progress how they can overcome cancer drug resistance by conjugating active drugs in combination with AuNPs through optimizing the effective drug concentration and removing the surface barrier.

Mortality Related Factors in Patients with Variceal Bleeding with MELD Score ≥ 18.

OBJECTIVE: To find and analyse the associated determinants of mortality in admitted patients in cirrhotic patients with MELD score >18 presenting in emergency department with variceal bleeding. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Department of Emergency Medicine, King Sultan Military Hospital Riyadh, Kingdom of Saudi Arabia, from July 2017 to January 2018. METHODOLOGY: A total of 235 patients fulfilling the inclusion criteria were enrolled in the study. Diagnosis of cirrhosis was made if the patients had platelets <150000/µl, PT >3 sec (prolonged), biochemical (reversal of ALT, AST ratio, albumin <3.5 g/dl) and ultrasongraphic coarse echotexture of liver and splenomegaly; and presence of all of the above variables and for at least six months. Variceal bleeding diagnosed on presentation and emergency endoscopy. MELD score was calculated by following formula. MELD = 3.78 [Ln serum bilirubin (mg/dL)] +11.2 [Ln INR] +9.57 [Ln serum creatinine (mg/dl)] +6.430 NR. Outcome of patients treatment was to record associated morbidity and mortality during follow-up period of one month. RESULTS: There were 156 (66.4%) male and 79 (33.6%) female cirrhotic patients. The mean age was 47.8 ±8.7 years. Out of 235 patients of liver cirrhosis, 47 (20.0%) expired during the hospital stay, while 188 (80.0%) patients survived and discharged from the hospital. Most of the cirrhotic patients were experienced with MELD score 18-20, i.e. 144 (61.3%) followed by 70 (29.8%) in 21-25 and 21 (8.9%) had the range of 26-30. In-hospital mortality rate was statistically insignificant (p>0.05) with respect to MELD scores. Probability of survival was 0.80. CONCLUSION: Liver cirrhosis with MELD score >18 and variceal bleeding is highly prevalent in young adult patients, more likely in male patients having duration of disease since >1 year to 3 years such that every 1 of 5 patients expired during the hospital stay. Probability of survival was 80%.

Mentha: A genus rich in vital nutra-pharmaceuticals-A review.

The genus Mentha comprises several aromatic species, which are cultivated world-over due to their distinct aroma and commercial value. In addition to traditional food flavoring uses, Mentha are well recognized for their folk medicinal uses, especially to treat cold, fever, and digestive and cardiovascular disorders. A number of biological activities such as antioxidant, antimicrobial, biopesticidal, antitumor, anticancer, antiviral, antiallergic, antiinflammatory, antihypertensive, and urease inhibitory activity have been ascribed to Mentha. The traditional pharmacological attributes of Mentha herbs can be linked to the occurrence of bioactive phytochemicals such as terpenoids, alcohols, rosmarinic acid, and antioxidant phenolics among others. A rich source of bioactives, different species of Mentha, can be explored as a promising candidate for the development of nutra-pharmaceuticals. This review covers the nutritional, phytochemical, and traditional medicinal aspects and multiple biological activities of some commonly available species of Mentha so as to explore their potential applications for nutra-pharmaceutical and cosmo-nutraceutical industry. Detailed chemical profile and pharmaceutical attributes of various Mentha essential oils are also covered. Moreover, based on computational analysis, quantitative chemical component-antioxidant activity relationship model is reviewed to predict and correlate structure-activity relationship of potential bioactives in selected Mentha essential oils leading to discovery and developmenmt of novel natural drugs.

The Dual Specificity Role of Transcription Factor FOXO in Type 2-diabetes and Cancer.

The FOXO (Forkhead box O) transcription factors are implicated in several signaling pathways and play a vital role in various cellular and physiological processes include for instance, ROS (reactive oxygen species) response, cell proliferation, regulation of programmed cell death, longevity, metabolism and cancer and regulation of cell cycle. In humans, the four FOXO family members are responsible for resemblance in their structure, regulation and functions. FOXO1 gene is highly expressed in adipose tissues and it affects the regulation of glycogenolysis and gluconeogenesis through insulin signaling. The gene of FOXO3 is highly expressed in the kidney, heart, spleen and brain and is characterized as diverse forkhead DNA-binding domain of transcription factors. The FOXO3 is a tumor suppressor gene and found to interact with p53, the trigger for apoptosis through BCl2 family genes and a regulator of Notch signaling pathway for the self-renewal of stem cells. Therefore, FOXOs remains to be a fascinating and potential target to acquire novel therapeutic approaches to cure cancer. This review will provide a comprehensive overview about the biology of FOXO proteins, which can be utilized for developing current therapeutic approaches to treat cancer.

Proscillaridin A Promotes Oxidative Stress and ER Stress, Inhibits STAT3 Activation, and Induces Apoptosis in A549 Lung Adenocarcinoma Cells.

Cardiac glycosides are natural compounds used for the treatment of cardiovascular disorders. Although originally prescribed for cardiovascular diseases, more recently, they have been rediscovered for their potential use in the treatment of cancer. Proscillaridin A (PSD-A), a cardiac glycoside component of Urginea maritima, has been reported to exhibit anticancer activity. However, the cellular targets and anticancer mechanism of PSD-A in various cancers including lung cancer remain largely unexplored. In the present study, we found that PSD-A inhibits growth and induces apoptosis in A549 lung adenocarcinoma cells. The anticancer activity of PSD-A was found to be associated with the activation of JNK, induction of ER stress, mitochondrial dysfunction, and inhibition of STAT3 activation. PSD-A induces oxidative stress as evidenced from ROS generation, GSH depletion, and decreased activity of TrxR1. PSD-A-mediated ER stress was verified by increased phosphorylation of eIF2α and expression of its downstream effector proteins ATF4, CHOP, and caspases-4. PSD-A triggered apoptosis by inducing JNK (1/2) activation, increasing bax/bcl-2 ratio, dissipating mitochondrial membrane potential, and inducing cleavage of caspases and PARP. Further study revealed that PSD-A inhibits both constitutive and inducible STAT3 activations and decreases STAT3 DNA-binding activity. Moreover, PSD-A-mediated inhibition of STAT3 activation was found to be associated with increased SHP-1 expression, decreased phosphorylation of Src, and binding of PSD-A with STAT3 SH2 domain. Finally, STAT3 knockdown by shRNA inhibited growth and enhanced apoptotic efficacy of PSD-A. Taken together, the data suggest that PSD-A could be developed into a potential therapeutic agent against lung adenocarcinoma.

Santamarine Inhibits NF-кB and STAT3 Activation and Induces Apoptosis in HepG2 Liver Cancer Cells via Oxidative Stress.

Sesquiterpene lactones have long been used in traditional Chinese medicines to treat inflammatory diseases. Recently, sesquiterpene lactone family compounds have been recognized as potential anticancer agents. Thus, it is necessary to explore new sesquiterpene lactones and their antitumor mechanism for cancer treatments. In the present study, we have explored the potential anti-cancer activity of a novel sesquiterpene lactone compound "santamarine" (STM) in HepG2 cells. It inhibited proliferation and induced apoptosis dose-dependently with IC50 ~ 70 µM. Induction of apoptosis was found to be linked with increased reactive oxygen species (ROS) generation, decreased activity of thioredoxin reductase (TrxR), glutathione (GSH) depletion, mitochondrial membrane potential (ΔΨm) dissipation, Bcl-2 family proteins modulation, cytochrome c release, caspases-9, -8 and -3 activation and PARP cleavage. Further mechanistic study demonstrated that STM inhibited the constitutive and TNF-α-induced translocation of NF-кB into nucleus by decreasing phosphorylation of IkB-α. Moreover, STM inhibited STAT3 activation by decreasing phosphorylation at tyrosine705. NAC pretreatment reversed the effect of STM-mediated cell death, NF-кB inhibition and blockage of STAT3 activity, indicating the involvement of oxidative stress in STM-mediated anticancer activity. Further studies are needed to explore the exact molecular mechanism of STM-induced apoptosis to develop it into a lead for treatment of liver cancer in future.