Death receptor pathway genes (Caspase and BID) expression analysis in cancerous cells in response to extracts of amla and turmeric.

Plant extracts antiproliferative effects were determined by using mammalian cells along the expression profile of Caspases 3, 8 and the BID gene of the death receptor-induced pathway. Two medicinal plants viz., Turmeric (Curcuma longa) and Amla (Emblica officinalis) extracts were examined for antiproliferative effect through Neutral Red-Dye uptake assay on Vero and MDA-MB 231 cell lines. A reverse transcriptase polymerase chain reaction was used to determine the expression of genes while GAPDH expression was used as an internal control. Expression of BID was up-regulated in methanolic turmeric extract-induced MDA-MB 231 cells while Caspases 3,8 expressions were the same in induced and uninduced MDA-MB 231 cells. Activated BID cleaved into tBID and activated the intrinsic pathway which caused death in methanolic turmeric extract-induced cancerous cells. Ethanolic extracts of turmeric exerted the strongest antiproliferative effects on Vero and methanolic extracts on MDA-MB 231 cells. The morphological studies of cell lines and gene expression analysis of turmeric methanolic extract-treated cells showed activation of apoptosis via converting BID into t-BID (intrinsic pathway) and activating Caspase-3 and Caspase-8 (extrinsic pathway). With the differential cytotoxicity and induction of apoptosis in induced cancer cells in comparison to uninduced cancerous cells, hence turmeric is a natural source of new anti-cancerous compounds.

Pistacia integerrima alleviated Bisphenol A induced toxicity through Ubc13/p53 signalling.

Exposure to environmental toxicants such as Bisphenol A (BPA) has raised serious health issues globally particularly in developing countries. It is ubiquitously used in the manufacturing of canned food and feeding bottles. BPA generated reactive oxygen species can lead to several diseases including cardiotoxicity. However, the endpoints stimulated in BPA cardiotoxicity yet need to be investigated. The current study was aimed to investigate the underlying molecular pathways which may contribute in revealing the protective effects of Pistacia integerrima against BPA induced oxidative stress. The dose of 100 µg/kg BW of BPA, 200 mg/kg BW P. integerrima, and 4 mg/kg BW melatonin was administered to Sprague Dawley rats. Present results of western blotting and qRT-PCR showed the increased expression of p53, PUMA and Drp1, while downregulation of Ubc13 in heart tissues of BPA treated group whereas the levels were reversed upon treatment with P. integerrima. The role of BPA in heart tissue apoptosis was further confirmed by the increased level of P-p53, cytochrome C and disrupted cellular architecture whereas the P. integerrima has shown its ameliorative potential by mitigating the adverse effects of BPA. Moreover, the oxidant, antioxidant, lipid, and liver markers profile has also revealed the therapeutic potential of P. integerrima by maintaining the levels in the normal range. However, melatonin has also manifested the normalized expression of apoptotic markers, biochemical markers, and tissue architecture. Conclusively, the data suggest that P. integerrima may be a potential candidate for the treatment of BPA induced toxicity by neutralizing the oxidative stress through Ubc13/p53 pathway.

Inhibitor of Chromosome Segregation in Pseudomonas aeruginosa from Fungal Extracts.

Chromosome segregation is an essential cellular process that has the potential to yield numerous targets for drug development. This pathway is presently underutilized partially due to the difficulties in the development of robust reporter assays suitable for high throughput screening. In bacteria, chromosome segregation is mediated by two partially redundant systems, condensins and ParABS. Based on the synthetic lethality of the two systems, we developed an assay suitable for screening and then screened a library of fungal extracts for potential inhibitors of the ParABS pathway, as judged by their enhanced activity on condensin-deficient cells. We found such activity in extracts of Humicola sp. Fractionation of the extract led to the discovery of four new analogues of sterigmatocystin, one of which, 4-hydroxy-sterigmatocystin (4HS), displayed antibacterial activity. 4HS induced the phenotype typical for parAB mutants including defects in chromosome segregation and cell division. Specifically, bacteria exposed to 4HS produced anucleate cells and were impaired in the assembly of the FtsZ ring. Moreover, 4HS binds to purified ParB in a ParS-modulated manner and inhibits its ParS-dependent CTPase activity. The data describe a small molecule inhibitor of ParB and expand the known spectrum of activities of sterigmatocystin to include bacterial chromosome segregation.

Organ Regeneration Through Stem Cells and Tissue Engineering.

Loss of organ and tissue due to injuries or diseases led to the development of regenerative therapies to decrease reliance on organ transplantations. It deals with employing the self-renewal ability of stem cells to differentiate into numerous lineages to assist in providing effective treatment for a range of various injuries and diseases. Regenerative engineering of organs or tissues represents an ever-expanding field that is aimed at developing biological replacements for dysfunctional organs or injured tissues. The critical issue, however, with the engineering of organs outside the human body is the insufficient availability of human cells, the absence of a suitable matrix with the same architecture and composition as the target tissue, and the maintenance of organ viability in the absence of the blood supply. The issue regarding the maintenance of the engineered organ viability can be solved using bioreactors consisting of mediums with defined chemical composition, i.e., nutrients, cofactors, and growth factors that can successively sustain the target cell's viability. Engineered extracellular matrices and stem cells to regenerate organs outside the human body are also being used. Clinically, various adult stem cell therapies are readily under practice. This review will focus on the regeneration of organs through various types of stem cells and tissue engineering techniques.

Ultra-Responses of Asphodelus tenuifolius L. (Wild Onion) and Convolvulus arvensis L. (Field Bindweed) against Shoot Extract of Trianthema portulacastrum L. (Horse Purslane).

Weed infestation is a prime challenge coupled with lowering crop production owing to their competition with crop plants for available resources such as nutrients, water, space, moisture, and sunlight. Among weed control methods, the implementation of synthetic herbicides offers an instant solution for getting rid of weeds; however, they are a direct source of potential hazards for humans and generate resistance against synthetic weedicides, making them less effective. Allelopathy is something that happens in nature that can be used as a weed control method that increases crop yield and decreases dependency on synthetic chemicals. The mode of action of some phytochemicals corresponds to synthetic herbicides. Due to this feature, allelochemicals are used as bio-herbicides in weed management and prove more environmentally friendly than synthetic weedicides. The present investigation aims to assess the ultra-responses of A. tenuifolius and C. arvensis, while growing them in a pot experiment. Various levels of shoot extract (L2, L3, and L4) of T. portulacastrum along with the L1 (distilled water) and L5 (synthetic herbicide) were applied to the weeds. Results indicated that aqueous extracts of shoot of T. portulacastrum significantly (p ≤ 0.05) affect all the measured traits of weeds and their effects were concentration specific. All morphological parameters were suppressed due to biotic stress with an increase in free amino acids and calcium ions along with a decline in metaxylem cell area and cortical thickness in the root, while the vascular bundle area increased. The shoot extract intrusive with metabolisms corresponded with the synthetic herbicide. It is concluded that Trianthema shoot extract has a powerful phytotoxic impact on weeds (A. tenuifolius and C. arvensis) and can be used in bio-herbicide production.

Association of Malnutrition With Weaning Practices Among Infants in Pakistan.

Background An appropriate diet is critical for the growth and development of infants, especially in the first two years of life. Despite considerable efforts made by government and local authorities to raise awareness, mothers still lack basic knowledge of weaning practices; as a result, infants face a growing number of health problems in their later years of life. This research aims to investigate the association between malnutrition and knowledge of different weaning practices among mothers and to study the factors influencing it. Methodology The current study was a cross-sectional study conducted at Mayo Hospital, Services Hospital, and Jinnah Hospital, Lahore, Pakistan between November 2019 and May 2020. A total of 200 infants of both genders aged between one and 12 months were included in the study. Knowledge and practices of complementary feeding by the mothers were assessed using a close-ended, pre-tested questionnaire. Results Mothers of 200 infants were interviewed and it was found that 79.5% of the infants were being breastfed while 24% never received breast milk. Among those who never received breast milk were given liquids (25%) and semi-solid foods (64.5%). Of the mothers, 8% started weaning at an early age (less than six months old) while the remaining started weaning at the age of six months or later and reported that their infants were either underweight or had reduced heights for that age. Based on the medical reports obtained from the hospital after getting parental consent, it was also found that the infants had distinct signs of deficiency of vitamins A and D, iron, and folate. Conclusions The majority of infants were breastfed, and, in most cases, weaning started at an age of less than six months. Most of the infants were fed semi-solid food as their first complementary food. Two-thirds of the infants were underweight for that age, and one-fifth had reduced heights. Based on deficiency statistics, mothers should be encouraged to start weaning at six months to have minimized malnourishment instances in infants.

Effects of plants extracts on the expression of major genes of JAK/STAT pathway.

This study analyzed the effects of the plant extracts (Citrus limon, Solanum lycopersicum, Zingiber officinale, Vitis vinifera and Allium sativum) on the growth of mammalian cells (Vero and MDA-MB-231) and evaluated the most effective plant extract for the expression of specific genes of the JAK/STAT pathway in human breast cancer cells. An antiproliferative bioassay involving neutral red-dye uptake was used to determine the anticancerous potential of plant extracts. In Vero cells, the ginger methanolic extract was least effective; whereas the lemon methanolic extract was more effective with 64 dilutions with IC50 51.42%. In MDA-MB-231 cells, the tomato and ginger methanolic, and grape water extracts were least effective, whereas lemon water extract was most effective with 32 dilutions with IC50 48.67%, by upregulating JAK1, JAK2, TYK2, IRF7 and IRF3 gene expressions of the JAK/STAT pathway. C. limon inhibited the growth of both Vero and MDA-MB 231 cells. It suggested that C. limon has anti-cancer potential by inducing the JAK/STAT pathway.