Correction: Abbas et al. Bioactive Compounds, Antioxidant, Anti-Inflammatory, Anti-Cancer, and Toxicity Assessment of Tribulus terrestris-In Vitro and In Vivo Studies. Antioxidants 2022, 11, 1160.

In the original publication [...].

Exploring the antimicrobial and cytotoxic potential of novel chloroquine analogues.

Aim: To synthesize novel chloroquine analogues and evaluate them for antimicrobial and cytotoxic potential. Methods: Novel analogues were synthesized from chloroquine by nucleophilic substitution reaction at the 4-amino position. Results: Analogue CS1 showed maximum antimicrobial potential (30.3 ± 0.15 mm zone) against Pseudomonas aeruginosa and produced a 19.2 ± 0.21 mm zone against Candida albicans, while CS0 produced no zone at the same concentration. Analogue CS9 has excellent cytotoxic potential (HeLa cell line), showing 100% inhibition (IC50 = 8.9 ± 1.2 µg/ml), compared with CS0 (61.9% inhibition at 30 µg/ml). Conclusion: These synthesized chloroquine analogues have excellent activity against different microbial strains and cervical cancer cell lines (HeLa) compared with their parent molecule.

Biochar-based organic fertilizers: Influence on yield and concentration of antioxidants in the stigma of saffron and rhizosphere bacterial diversity of slightly saline and non-saline soils.

Being the most expensive spice, saffron has great economic importance. This crop grows well in cold arid deserts. Salinity is one of the important limiting factors for the cultivation of this crop. However, the use of composted manured and co-composted biochar and fertilizers can play a role in attenuating the salinity stress on this crop. In this two-year field study, manures from three sources: sheep and goat (SG), cow and buffalo (FYM), and poultry (PM) farms, and their co-compost with slow-pyrolyzed wood-derived biochar (B) were used for saffron cultivation in slightly saline (electrical conductivity 1.95 dS m-1) and non-saline soils. Yield and concentration of antioxidants of stigma and bacterial diversity in the rhizosphere of this crop, under salinity and non-salinity conditions, were evaluated. Results revealed that in non-saline soil of first-year crops, all fertilizers decreased the yield of stigma than control by 15-49 % (P ≤ 0.05) but increased the concentration of carotenoids and total polyphenolics (P ≤ 0.05). In saline soil, no difference in yield was observed between treatments for the first-year crop; however, for the second-year crop, as compared to control, PM and FYM significantly increased yield by 41 % and 44 % respectively, whereas FYM also increased the concentration of total polyphenolics (P ≤ 0.05). The FYM fertilizer was found suitable for the yield and quality of saffron stigma for second-year crops in both soils (non-saline and saline). The observed OTUs, Chao1, Fischer, and ACE indexes based on 16 s rRNA metagenomic analysis revealed 2-4 times greater bacterial diversity in the rhizosphere soil of PM-B and SG-B treatments than in the control. Furthermore, 347 bacterial species were found in PM-B- or SG-B-amended soils absent in control treatments.

Effect of Growth Stages and Lactic Acid Fermentation on Anti-Nutrients and Nutritional Attributes of Spinach (Spinacia oleracea).

Spinach (Spinacia oleracea) is a winter-season green, leafy vegetable grown all over the world, belonging to the family Amaranthus, sub-family Chenopodiaceae. Spinach is a low-caloric food and an enormous source of micronutrients, e.g., calcium, folates, zinc, retinol, iron, ascorbic acid and magnesium. Contrarily, it also contains a variety of anti-nutritional factors, e.g., alkaloids, phytates, saponins, oxalates, tannins and many other natural toxicants which may hinder nutrient-absorption. This study was aimed at investigating the effect of fermentation on improving the nutrient-delivering potential of spinach and mitigating its burden of antinutrients and toxicants at three growth stages: the 1st growth stage as baby leaves, the 2nd growth stage at the coarse stage, and the 3rd growth stage at maturation. The results revealed the significant (p < 0.05) effect of fermentation on increasing the protein and fiber content of spinach powder from 2.53 to 3.53% and 19.33 to 22.03%, respectively, and on reducing total carbohydrate content from 52.92 to 40.52%; the effect was consistent in all three growth stages. A significant decline in alkaloids (6.45 to 2.20 mg/100 g), oxalates (0.07 mg/100 g to 0.02 mg/100 g), phytates (1.97 to 0.43 mg/100 g) and glucosinolates (201 to 10.50 µmol/g) was observed as a result of fermentation using Lactiplantibacillus plantarum. Fermentation had no impact on total phenolic content and the antioxidant potential of spinach, as evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric-reducing antioxidant power (FRAP) assays. This study proposes fermentation as a safer bioprocess for improving the nutrient-delivering potential of spinach, and suggests processed powders made from spinach as a cost-effective complement to existing plant proteins.

The Comparative Effect of Lactic Acid Fermentation and Germination on the Levels of Neurotoxin, Anti-Nutrients, and Nutritional Attributes of Sweet Blue Pea (Lathyrus sativus L.).

Grass pea (Lathyrus sativus L.), an indigenous legume of the subcontinental region, is a promising source of protein and other nutrients of health significance. Contrarily, a high amount of ß-N-oxalyl-l-α,ß-diaminopropionic acid (ß-ODAP) and other anti-nutrients limits its wider acceptability as healthier substitute to protein of animal and plant origin. This study was aimed at investigating the effect of different processing techniques, viz. soaking, boiling, germination, and fermentation, to improve the nutrient-delivering potential of grass pea lentil and to mitigate its anti-nutrient and toxicant burden. The results presented the significant (p < 0.05) effect of germination on increasing the protein and fiber content of L. sativus from 22.6 to 30.7% and 15.1 to 19.4%, respectively. Likewise, germination reduced the total carbohydrate content of the grass pea from 59.1 to 46%. The highest rate of reduction in phytic acid (91%) and ß-ODAP (37%) were observed in germinated grass pea powder, whereas fermentation anticipated an 89% reduction in tannin content. The lactic acid fermentation of grass pea increased the concentration of calcium, iron, and zinc from 4020 to 5100 mg/100 g, 3.97 to 4.35 mg/100 g, and 3.52 to 4.97 mg/100 g, respectively. The results suggest that fermentation and germination significantly (p < 0.05) improve the concentration of essential amino acids including threonine, leucine, histidine, tryptophan, and lysine in L. sativus powder. This study proposes lactic acid fermentation and germination as safer techniques to improve the nutrient-delivering potential of L. sativus and suggests processed powders of the legume as a cost-effective alternative to existing plant proteins.

Administration of α-lipoic acid and silymarin attenuates aggression by modulating endocrine, oxidative stress and inflammatory pathways in mice.

Aggression, a highly prevalent behavior among all the psychological disorders having strong association with psychiatric imbalance, neuroendocrine changes and neurological disturbances (including oxidative stress & neuroinflammation) require both pharmacological and non-pharmacological treatments. Focusing the preclinical neuroendocrine determinants of aggression, this interventional study was designed to elucidate the curative effect of antioxidants on aggression in male mice. Adult albino male mice (n = 140) randomly divided into two main treatment groups for α-lipoic acid (ALA) and silymarin with 5 subgroups (n = 10) for each curative study, namely control, disease (aggression-induced), standard (diazepam, 2.5 mg/kg), low dose (100 mg/kg) and high dose (200 mg/kg) treatment groups of selected antioxidants. Resident-intruder paradigm and levodopa (L-dopa 375 mg/kg, p.o.) induced models were used for aggression. Effect of antioxidant treatment (i.e., 21 days bid) on aggression was assessed by evaluating the changes in aggressive behavior, oxidative stress biomarkers superoxide dismutase, catalase, glutathione, nitrite and malondialdehyde (SOD, CAT, GSH, nitrite & MDA), neurotransmitters (dopamine, nor-adrenaline and serotonin), pro-inflammatory cytokines tumor necrosis factor-α and interleukin- 6 (TNF-α & IL-6) along with serum testosterone examination. This study showed potential ameliorative effect on aggressive behavior with both low (100 mg/kg) and high (200 mg/kg) doses of antioxidants (ALA & silymarin). Resident-intruder or L-dopa induced aggression in male mice was more significantly tuned with ALA treatment than silymarin via down regulating both oxidative stress and inflammatory biomarkers. ALA also exhibited notable effects in managing aggression-induced disturbances on plasma testosterone levels. In conclusion, ALA is more effective than silymarin in attenuating aggression in mice.

Toxicity profiling of Burgmansia aurea Lagerh. Leaves using acute and sub-acute toxicity studies in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Toxicity studies in appropriate animal models are an integral and very important component of pre-clinical studies in drug development. Brugmansia aurea lagerh. is used for both medicinal and non-medical purposes, including treating skin infections, different types of physical discomfort, inflammation, cough, hallucinations, and evil protection. AIM OF THE STUDY: This study was designed to detect any hazardous effects of B. aurea on animals and find out its LD50. MATERIALS & METHODS: An acute toxicity study was performed to find out the LD50 value and sub-acute toxicity study was performed to find out the toxicity on repeated dose administration till 28 days. Both studies were performed according to the organization of economic cooperation and development (OECD) 425 and 407 respectively. For the acute oral toxicity study, animals were divided into two groups, group I normal control (NC) and group II received a 2000mg/kg dose of B.aurea leaves extract. In the sub-acute toxicity study, male and female animals were divided into eight groups, I-IV for males and V-VIII for females received control, 100, 200 & 400mg/kg B. aurea leaves extract respectively. Hematological and biochemical markers were estimated at the end of each study. RESULTS: Results revealed that no mortality and morbidity were observed in acute oral as well as sub-acute toxicity studies. Oxidative stress markers were increased significantly in all organs of the treatment groups in both studies. Animals significantly decreased their food and water intake in an acute oral toxicity study. A slight difference in renal function tests was observed in the acute oral toxicity study when compared with the normal control group. No significant change in histopathology was observed in both studies on selected organs. CONCLUSION: This study concluded that B. aurea can be safely used for pharmacological purposes.

Combined antidiabetic potential of camel milk yogurt with Cinnamomum verum and Stevia rebaudiana by using rodent modelling.

This study aimed to evaluate anti-diabetic potential of functional camel milk yogurt enriched with Cinnamomum verum and Stevia rebaudiana that not only mask its peculiar flavour rather have an antidiabetic effect as well. Sixty-three pathogen free STZ-induced albino Wistar rats were categorized into 7 groups on the basis of treatments. From each treatment group three animals were dissected periodically at 0, 7 and 21 days of study to determine the effect of all treatments on physicochemical parameters, serum glucose, serum chemistry and haematology. The study revealed that the mean blood glucose level in the untreated control group was within normal range (100-108 mg/dl) while there was noticeable decrease in mean blood glucose level of all the treated groups during three weeks' trial. Decline in blood glucose level (46%) was higher in animal group containing functional camel milk yogurt (T4) at 3rd week of trial as compared to other treatments.

The wound healing potential of Hedychium spicatum Sm. and Zinnia peruviana (L.) ethanolic extracts against excision wound model in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants used for wound healing, are key to unlock the doors for combating the resistance of pathogens by provision of new source of compounds. AIM OF THE STUDY: This study is aimed to evaluate and compare the wound healing properties of ethanolic extract of Hedychium spicatum Sm. rhizome and of Zinnia peruviana's leaves and roots. MATERIALS & METHODS: Albino rats were divided into 10 groups (n = 6), control, positive control, negative control, untreated, Hedychium spicatum Sm. (125 mg/kg), Hedychium spicatum Sm (250 mg/kg), Zinnia peruviana (L.)(Leaves) (125 mg/kg), Zinnia peruviana (L.) (Leaves) (250 mg/kg), Zinnia peruviana (L.)(Roots) (125 mg/kg), Zinnia peruviana (L.)(Roots) (250 mg/kg) respectively. Excision wound of 1.5 cm wound was inflicted on the dorsal side of each rat except control group. 5% CMC gel, fusidic acid and extract gels were applied topically once daily on the wound area which was measured at intervals of 3 days until epithelization and complete wound closure. Different biochemical markers were analyzed in both blood and skin to validate the wound healing potential of these plants. RESULTS: Topical application of an ethanolic extract of Hedychium spicatum Sm. (250 mg/kg) had significant (p ˂ 0.001) rate of wound healing and reduced epithelization period. Marked amelioration of hydroxyproline content, remarkable results on histopathological changes, reduction in oxidative stress was observed with Hedychium spicatum Sm. ethanolic extract at dose level of 250 mg/kg in comparison with untreated group. CONCLUSION: This study concluded that the Hedychium spicatum Sm. rhizome ethanolic extract gel is effective in wound repair and may possess potential for the development of dermatologic preparation for topical diseases.

Inhibition of Oxidative Stress and the NF-κB Pathway by a Vitamin E Derivative: Pharmacological Approach against Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder. In this study, PD was induced via (ip) injection of haloperidol (1 mg/kg/day). Animals were divided into seven groups (n = 70). Group I received the vehicle carboxymethylcellulose (CMC; 0.5%), group II was treated with designated 1 mg/kg haloperidol, and group III received the standard drug Sinemet (100 mg/kg), while groups IV-VII received a tocopherol derivative (Toco-D) at dose levels of 5, 10, 20, and 40 mg/kg, respectively, via the oral route. All groups received haloperidol for 23 consecutive days after their treatments except the control group. The improvement in locomotor activity and motor coordination was evaluated by using behavioral tests. Oxidative stress markers, neurotransmitters, and monoamine oxidase B (MAO-B) as well as NF-κB levels in the whole brain were measured. mRNA expression analysis of α-synuclein was carried out using the PCR technique. Toco-D at 20 mg/kg showed the maximum improvement in locomotor activity. The levels of antioxidant enzymes and neurotransmitters were also increased by the treatment with Toco-D. Inflammatory cytokine levels and mRNA expression of α-synuclein were decreased by Toco-D in treated animals. This study concluded that Toco-D might be effective in the improvement of locomotor activity and motor coordination in haloperidol-induced PD.

Effect of Thermal and Non-Thermal Processing on Nutritional, Functional, Safety Characteristics and Sensory Quality of White Cabbage Powder.

This study was aimed to improve nutritional, functional and consumer safety aspects of cabbage powder (CP). White cabbage (Brassica oleracea var. capitata f. alba) was dehydrated to CP following microwave heating, blanching, alkali or acid washing treatments. The results for nutrients and mineral composition of raw and processed CP elucidated raw CP to exhibit significantly (p < 0.05) higher amounts of protein (12.2%), dietary fiber (25.2%), Na (52 mg/100 g), Ca (355 mg/100 g), K (286 mg/100 g), Fe (14 mg/100 g) and Zn (32 mg/100 g). Among different processing techniques, microwave treatment resulted in a higher rate of reduction for alkaloids, oxalates, tannins and phytates contents, i.e., 77%, 85%, 85%, and 86%, respectively. Likewise, microwave treatment was found more effective in reducing residual levels of neonicotinoids, pyrethroids, organophosphates including imidacloprid, cypermethrin, bifenthrin, chlorpyrifos and deltamethrin in cabbage in the range of 0.98−0.12 ppm, 1.22−0.23 ppm, 1.03−0.15 ppm, 1.97−0.43 ppm, and 2.12−0.36 ppm, respectively. CP supplementation at the rate of 5% in unleavened flatbreads was observed to maintain textural and sensory attributes of the product. The results suggest microwave heating as a cost-effective technique to reduce toxicants load in cabbage powder. Further, ~5% supplementation of CP in wheat flour may also improve nutritional and functional properties of the baked goods.

Establishing Height-for-Age Z-Score Growth Reference Curves and Stunting Prevalence in Children and Adolescents in Pakistan.

Height-for-age Z-score (HAZ) curves are widely used for detecting children with stunting. The aim of this study was to provide smoothed HAZ growth reference values and their curves for Pakistani children and adolescents aged 2-18 years. The prevalence of stunting in Pakistani children was determined. A total of 10,668 healthy Pakistani participants were included. Information related to age, sex, city of residence and height (cm) was used. Age- and sex-specific smoothed HAZ growth reference values and associated graphs were obtained using the lambda-mu-sigma (LMS) method. The prevalence of stunting was calculated by applying WHO 2007 and USCDC 2000 height-for-age references and local reference of the study population. In both sexes, the smoothed HAZ curves increased with age. For 2 and 3 years of age, the height values of the girls were greater than those of the boys. The boys were then taller than the girls. Comparing our median height (z = 0) growth reference data from WHO, USCDC and corresponding data from other countries, Pakistani children and adolescents have significantly different reference values than their counterparts in the reference group. A marked overestimation of the prevalence of stunting was observed (10.8% and 17.9% according to WHO and USCDC, respectively) compared to the local reference (3.0%). It is recommended that the prevalence of stunting in children and adolescents is determined by applying local height growth references to plan health strategies and treatments in the local population.

Antioxidant Effect of Ocimum basilicum Essential Oil and Its Effect on Cooking Qualities of Supplemented Chicken Nuggets.

A commonly observed chicken meat issue is its lipid oxidation that leads to deterioration of its organoleptic and nutritional properties and its further-processed products. Basil (Ocimum basilicum L.) is one of the traditional culinary herbs exhibiting food preservation properties. The current study investigated the essential oil composition, antioxidant activity and in vitro cytotoxic capacity of the essential oil of basil indigenous to Pakistan. GC-MS analysis of the essential oil revealed the presence of 59 compounds that constituted 98.6% of the essential oil. O. basilicum essential oil (OB-EO) exhibited excellent antioxidant activity, i.e., IC50 5.92 ± 0.15 µg/mL as assayed by the DPPH assay, 23.4 ± 0.02 µmoL Fe/g by FRAP, and 14.6 ± 0.59% inhibition by H2O2. The brine shrimp lethality assay identified an average mortality of ~18% with OB-EO at 10-1000 µg/mL, while that of the same concentration range of the standard drug (etoposide) was 72%. OB-EO was found to be non-toxic to HeLa and PC-3 cell lines. TBARS contents were significantly decreased with increase of OB-EO in chicken nuggets. The lowest TBARS contents were recorded in nuggets supplemented with 0.3% OB-EO, whereas the highest overall acceptability score was marked to the treatments carrying 0.2% OB-EO. The results suggest OB-EO as a promising carrier of bioactive compounds with a broad range of food preservation properties, and which has a sensory acceptability threshold level for chicken nuggets falling between 0.2-0.3% supplementation. Future research must investigate the antibacterial impact of OB-EO on meat products preserved with natural rather than synthetic preservatives.

Antidiabetic effects of Brugmansia aurea leaf extract by modulating the glucose levels, insulin resistance, and oxidative stress mechanism.

Background: Ethnopharmacological relevance: Brugmansia, a genus of the Solanaceae family, has historically been utilized in many different parts of the world as an anti-inflammatory for treating skin infections, wounds, and bodily aches and pains. The current study aimed to investigate the potential benefits of a methanolic extract of Brugmansia aurea in the management of diabetes and underlying complications in alloxanized-induced diabetic rats. Materials and methods: Animals were divided into nine groups (n = 6). Four groups received different standard oral hypoglycemic agents; three groups received 100, 200, and 400 mg/kg of B. aurea leaf extract for six consecutive weeks, and the remaining two were normal and disease control groups. All groups received alloxan (150 mg/kg) except for the normal control. Only those animals whose glucose levels were raised to 200 mg/dl were selected for the study. After a 6-week dosage period, various biochemical parameters, as well as HbA1c, antioxidant profile, oral glucose tolerance test (OGTT), insulin sensitivity, histopathology, and insulin resistance, were measured and compared with the untreated diabetic group. Results: Brugmansia aurea leaf extract at a dose of 400 mg/kg showed potent antidiabetic activity by reducing blood glucose levels (p < 0.001) after 6 weeks of treatment. OGTT data showed that B. aurea exhibited significant (p < 0.001) glucose tolerance by significantly reducing blood glucose levels in just 2 h post-treatment. Other tests showed that plant extract significantly increased (p < 0.001) insulin sensitivity and decreased (p < 0.001) insulin resistance. The biochemical profile showed reduced triglyceride and cholesterol, while the antioxidant profile showed restoration of antioxidant enzymes in the pancreas, kidney, and liver tissues of treated rats. Conclusion: The present study indicated that crude extracts of B. aurea increase insulin sensitivity and reduce hyperlipidemia in diabetic rats, which rationalizes the traditional medicinal use of this plant as an antidiabetic agent.

Prospective Evaluation of an Amide-Based Zinc Scaffold as an Anti-Alzheimer Agent: In Vitro, In Vivo, and Computational Studies.

Alzheimer's disease is the most common progressive neurodegenerative mental disorder associated with loss of memory, decline in cognitive function, and dysfunction of language. The prominent pathogenic causes of this disease involve deposition of amyloid-ß plaques, acetylcholine neurotransmitter deficiency, and accumulation of neurofibrillary tangles. There are multiple pathways that have been targeted to treat this disease. The inhibition of the intracellular cyclic AMP regulator phosphodiesterase IV causes the increase in CAMP levels that play an important role in the memory formation process. Organometallic chemistry works in a different way in treating pharmacological disorders. In the field of medicinal chemistry and pharmaceuticals, zinc-based amide carboxylates have been shown to be a preferred pharmacophore. The purpose of this research work was to investigate the potential of zinc amide carboxylates in inhibition of phosphodiesterase IV for the Alzheimer's disease management. Swiss Albino mice under controlled conditions were divided into seven groups with 10 mice each. Group I was injected with carboxymethylcellulose (CMC) at 1 mL/100 g dose, group II was injected with Streptozotocin (STZ) at 3 mg/kg dose, group III was injected with Piracetam acting as a standard drug at 200 mg/kg dosage, while groups IV-VII were injected with a zinc scaffold at the dose regimen of 10, 20, 40, and 80 mg/kg through intraperitoneal injection. All groups except group I were injected with Streptozotocin on the first day and third day of treatment at the dose of 3 mg/kg through an intracerebroventricular route to induce Alzheimer's disease. Afterward, respective treatment was continued for all groups for 23 days. In between the treatment regimen, groups were analyzed for memory and learning improvement through various behavioral tests such as open field, elevated plus maze, Morris water maze, and passive avoidance tests. At the end of the study, different biochemical markers in the brain were estimated like neurotransmitters (dopamine, serotonin and adrenaline), oxidative stress markers (superoxide dismutase, glutathione, and catalase), acetylcholinesterase (AchE), tau proteins, and amyloid-ß levels. A PCR study was also performed. Results showed that the LD50 of the zinc scaffold is greater than 2000 mg/kg. Research indicated that the zinc scaffold has the potential to improve the memory impairment and learning behavior in Alzheimer's disease animal models in a dose-dependent manner. At the dose of 80 mg/kg, a maximum response was observed for the zinc scaffold. Maximum reduction in the acetylcholinesterase enzyme was observed at 80 mg/kg dose, which was further strengthened and verified by the PCR study. Oxidative stress was restored by the zinc scaffold due to the significant activation of the endogenous antioxidant enzymes. This research ended up with the conclusion that the zinc-based amide carboxylate scaffold has the potential to improve behavioral disturbances and vary the biochemical markers in the brain.

Antioxidant, Cytotoxic, and Antimicrobial Potential of Silver Nanoparticles Synthesized using Tradescantia pallida Extract.

Silver nanoparticles have received much attention, due to their wide range of biological applications as an alternative therapy for disease conditions utilizing the nanobiotechnology domain for synthesis. The current study was performed to examine the antioxidant, anticancer, antibacterial, and antifungal potential of biosynthesized silver nanoparticles (TpAgNPs) using plant extract. The TpAgNPs were produced by reacting the Tradescantia pallida extract and AgNO3 solution in nine various concentration ratios subjected to bioactivities profiling. According to the current findings, plant extract comprising phenolics, flavonoids, and especially anthocyanins played a critical role in the production of TpAgNPs. UV-visible spectroscopy also validated the TpAgNP formation in the peak range of 401-441 nm. Further, the silver ion stabilization by phytochemicals, face-centered cubic structure, crystal size, and spherical morphology of TpAgNPs were analyzed by FTIR, XRD, and SEM. Among all TpAgNPs, the biosynthesized TpAgNP6 with a medium concentration ratio (5:10) and the plant extract had effective antioxidant potentials of 77.2 ± 1.0% and 45.1 ± 0.5% free radical scavenging activity, respectively. The cytotoxic activity of TpAgNP6 in comparison to plant extract for the rhabdomyosarcoma cell line was significantly the lowest with IC50 values of 81.5 ± 1.9 and 90.59 ± 1.6 µg/ml and cell viability % of 24.3 ± 1.62 and 27.4 ± 1.05, respectively. The antibacterial and antifungal results of TpAgNPs revealed significant improvement in comparison to plant extract, i.e., minimum inhibition concentration (MIC) 64 µg/ml against Gram-negative Pseudomonas aeruginosa while, in the case of antifungal assay, TpAgNP6 was active against Candida parapsilosis. These TpAgNPs play a crucial role in determining the therapeutic potential of T. pallida due to their biological efficacy.

Patient Derived Organoids Confirm That PI3K/AKT Signalling Is an Escape Pathway for Radioresistance and a Target for Therapy in Rectal Cancer.

Objectives: Partial or total resistance to preoperative chemoradiotherapy occurs in more than half of locally advanced rectal cancer patients. Several novel or repurposed drugs have been trialled to improve cancer cell sensitivity to radiotherapy, with limited success. We aimed to understand the mechanisms of resistance to chemoradiotherapy in rectal cancer using patient derived organoid models. Design: To understand the mechanisms underlying this resistance, we compared the pre-treatment transcriptomes of patient-derived organoids (PDO) with measured radiotherapy sensitivity to identify biological pathways involved in radiation resistance coupled with single cell sequencing, genome wide CRISPR-Cas9 and targeted drug screens. Results: RNA sequencing enrichment analysis revealed upregulation of PI3K/AKT/mTOR and epithelial mesenchymal transition pathway genes in radioresistant PDOs. Single-cell sequencing of pre & post-irradiation PDOs showed mTORC1 and PI3K/AKT upregulation, which was confirmed by a genome-wide CRSIPR-Cas9 knockout screen using irradiated colorectal cancer (CRC) cell lines. We then tested the efficiency of dual PI3K/mTOR inhibitors in improving cancer cell sensitivity to radiotherapy. After irradiation, significant AKT phosphorylation was detected (p=0.027) which was abrogated with dual PI3K/mTOR inhibitors and lead to significant radiosensitisation of the HCT116 cell line and radiation resistant PDO lines. Conclusions: The PI3K/AKT/mTOR pathway upregulation contributes to radioresistance and its targeted pharmacological inhibition leads to significant radiosensitisation in CRC organoids, making it a potential target for clinical trials.

Bioactive Compounds, Antioxidant, Anti-Inflammatory, Anti-Cancer, and Toxicity Assessment of Tribulus terrestris-In Vitro and In Vivo Studies.

Tribulus terrestris L. belongs to the family Zygophyllaceae and integral part of various ancient medicinal systems including Chinese, Indian, and European to combat various health ailments. The aim of the present study was to assess the phytochemical constituents, in vitro antioxidant activity using DPPH, FRAP, and H2O2 assays, in vitro anticancer activity using MTT assay, and in vitro and in vivo anti-inflammatory properties of T. terrestris. The acute and sub-acute toxicity of extracts exhibiting most biological potential was examined using murine models. Liquid-liquid partitioning followed by RP-HPLC sub-fraction of crude extract was performed. After that, ESI-MS/MS analysis was done for the timid identification of bioactive metabolites responsible for bioactivities of sub-fractions and HPLC analysis to quantify the compounds using external standards. Among all extracts, T. terrestris methanol extract was noted to hold maximum phenolic (341.3 mg GAE/g) and flavonoid (209 mg QE/g) contents, antioxidant activity in DPPH (IC50 71.4 µg/mL), FRAP (35.3 mmol/g), and H2O2 (65.3% inhibition) assays, anti-inflammatory activities in vitro at 400 µg/mL (heat-induced hemolysis, % inhibition 68.5; egg albumin denaturation, % inhibition 75.6%; serum albumin denaturation, % inhibition 80.2), and in vivo at 200 mg/kg (carrageenan-induced paw edema, % inhibition 69.3%; formaldehyde-induced paw edema, % inhibition 71.3%) and anticancer activity against breast cancer cell (MCF-7) proliferation (IC50 74.1 µg/mL). Acute and sub-acute toxicity studies recorded with no change in body weight, behavior, hematological, serum, and histopathological parameters in treated rats with T. terrestris methanol extracts when compared to control group. Fraction B obtained through liquid-liquid partitioning resulted in more bioactive potential as compared to the parent methanol extract. RP-HPLC analysis of fraction B resulted with four sub-fractions (TBTMF1-TBTMF4), wherein TBTMF3 delineated notable bioactive capabilities as compared to other fractions and parent methanol extract. ESI-MS/MS analysis of TBTMF3 resulted with tentative identification of myricetin, rutin, liquitrigenin, physcion, and protodioscin. It can be stated that T. terrestris is a potential bearing herb and findings of current study further verify the claims made in ancient medicinal systems. However, after investigation of each identified compound, it must be considered for drug discovery.

Prevalence and determinants of anemia among resident female university students from Southern Punjab, Pakistan.

Health and nutritional status of the women of reproductive age (WRA) is expected to be influenced with women literacy status alongside other sociodemographic indicators. However, data are scant to validate if literate young women have lower incidence of anemia prevalence. Nexus to the problem stated, a cross-sectional study was conducted on 1,541 female resident university students (FRUS) aged 17-35 years from a public sector university located in Southern Punjab, Pakistan. Hemoglobin (Hb) led screening for anemia was performed followed by nutritional assessment and structured questionnaire-based sociodemographic and dietary assessment. The data generated were analyzed using independent t-test, Chi-square, and response surface regression models. Response rate for the prevalence of anemia in FRUS was 38 percent with mean Hb levels 10.5 g/dL. With a significant effect (p = .001) of participants' weight on anemia prevalence, 22.45 percent of the sample population was recorded as underweight. Sociodemographic and dietary parameters analyzed suggested low daily food expenditure (x2 = 20.59; p = .000) and reduced intake of meat (x2 = 12.14; p = .01), beans & pulses (x2 = 18.56; p = .001) to significantly influence rate of anemia prevalence in FRUS. The study concludes high prevalence rate of anemia among FRUS to strongly relate with students' low monthly stipend, little daily food expenditure, and substandard dietary quality.

Anticandidal activity of green synthesised silver nanoparticles and extract loaded chitosan nanoparticles of Euphorbia prostata.

This study aimed to synthesize the silver nanoparticles (SNPs) and loaded chitosan nanoparticles (LCNPs) using Euphorbia prostata based on their anticandidal activity. Antioxidant capacity and the total phenolic and total flavonoid content of plant samples and synthesized nanoparticles (NPs) were also evaluated. SNPs and LCNPs were prepared, respectively using chemical reduction of silver salt solution and ionotropic gelation method. The anticandidal activity was assessed by broth micro-dilution method and the antioxidant activity was determined using free-radical scavenging assays. The synthesized NPs after the optimization process were found to be spherical with sizes ranging from 12 to 100 nm. Spectroscopic analysis of NPs showed the appearance of peaks in prescribed wavelength ranging between 402 and 493 nm. The synthesized NPs showed potent anticandidal activity compared to the free extract. The SNPs formulations NpEPM 7.5 and NpEPMR 7.5, showed significantly low MIC values ranging between 2 and 128 µg/mL. In the case of LCNPs, NpEPM (4:1) and NpEPME (4:1) also showed lower MIC values ranging from 32 to 256 µg/mL. The plant samples as well as NPs showed antioxidant potential. In addition, plant extracts and NPs possess the potent biological potential and can be further investigated through in vivo experiments.