Isolation and characterization of novel cadmium-resistant Escherichia fergusonii ZSF-15 from industrial effluent for flocculant production and antioxidant enzyme activity.

Cadmium (Cd) is a highly toxic metal that frequently contaminates our environment. In this study, the bioflocculant-producing, cadmium-resistant Escherichia fergusonii ZSF-15 was characterized from Paharang drain, Bawa Chak, Faisalabad, Pakistan. The Cd-resistant E. fergusonii was used to determine the bioflocculant production using yeast-peptone-glycerol medium (pH 6.5) supplemented with 50 mg L-1 of Cd. The culture was incubated for 3 days at 37 °C in a rotary shaker at 120 rpm. The fermentation broth was centrifuged at 4000 g for 10 min after the incubation period. The maximum flocculating activity by isolate ZSF-15 was found to be 71.4% after 48 h of incubation. According to the Fourier transform infrared spectroscopy analysis, the bioflocculant produced by strain ZSF-15 was comprised of typical polysaccharide and protein, i.e. hydroxyl, carboxyl, and amino groups. The strain ZSF-15 exhibited bioflocculant activity at range of pH (6-8) and temperature (35-50℃). Maximum flocculation activity (i.e. 71%) was observed at 47℃, whereas 63% flocculation production was observed at pH 8. In the present study, antioxidant enzyme profile of ZSF-15 was also evaluated under cadmium stress. A significant increase in antioxidant enzymes including superoxide dismutase (118%) and ascorbate peroxidase (28%) was observed, whereas contents of catalase (86%), glutathione transferase (13%), and peroxidase (8%) were decreased as compared to control.

PIAS family in cancer: from basic mechanisms to clinical applications.

Protein inhibitors of activated STATs (PIAS) are proteins for cytokine signaling that activate activator-mediated gene transcription. These proteins, as versatile cellular regulators, have been described as regulators of approximately 60 proteins. Dysregulation of PIAS is associated with inappropriate gene expression that promotes oncogenic signaling in multiple cancers. Multiple lines of evidence have revealed that PIAS family members show modulated expressions in cancer cells. Most frequently reported PIAS family members in cancer development are PIAS1 and PIAS3. SUMOylation as post-translational modifier regulates several cellular machineries. PIAS proteins as SUMO E3 ligase factor promotes SUMOylation of transcription factors tangled cancer cells for survival, proliferation, and differentiation. Attenuated PIAS-mediated SUMOylation mechanism is involved in tumorigenesis. This review article provides the PIAS/SUMO role in the modulation of transcriptional factor control, provides brief update on their antagonistic function in different cancer types with particular focus on PIAS proteins as a bonafide therapeutic target to inhibit STAT pathway in cancers, and summarizes natural activators that may have the ability to cure cancer.

Investigation of gadolinium doped manganese nano spinel ferrites via magnetic hypothermia therapy effect towards MCF-7 breast cancer.

Magnetic spinel ferrite nanoparticles (MSF-NPs) are potential candidates for biomedical applications, especially in cancer diagnosis and therapy due to their excellent physiochemical and magnetic properties. In the current study, MSF-NPs were fabricated by sol-gel auto combustion method. The crystal structure and surface morphology were confirmed by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The magnetic properties were studied by VSM (vibrating sample magnetometer). As increasing Gd3+ concentration, the saturation magnetization values decreased from (17.8-2.3) emu/g, while the coercivity decreased from (499-133) Oe at room temperature. Finally, the fabricated MSF-NPs were tested against anticancer activity by MTT assay. The IC50 = 21.27 µg/mL value was observed, showing the strong antiproliferative activity of these nanoparticles. These results suggested that the obtained MSF-NPs would be useful for remote-controlled hyperthermia therapy for cancer treatment and MRI application due to their excellent magnetic properties. These distinct properties make MSF-NPs most suitable for cancer treatment and bright Contrast Agents (T1-MRI).

Hepatoprotective effects of almond shells against carbon tetrachloride induced liver injury in albino rats.

Liver injury is a prevalent pathological process that can give rise to conditions such as fatty liver, cirrhosis, fibrosis, and even cancer. It has been observed that plants and natural products possess significant protective effects against liver injury. Current study was performed to investigate the efficacy of almonds shell against carbon tetrachloride (CCl4) induced hepatotoxicity in rat model. As almonds shell contain a large variety of phenolic and flavonoid compounds, which are largely associated with antioxidant and hepatoprotective properties. For this purpose, screening of small-scale library of twenty plant extracts was performed for evaluation of antioxidant potential by DPPH assay. The data revealed that almonds shell extract (ASEE) exhibited potent antioxidant activity. This potent extract was further evaluated for hepatoprotective activity in in vivo rat model on 30 rats, divided into 6 groups of 5 rats each. On 29th day all rats were sacrificed and blood serum was collected for further analysis. Liver tissues were also preserved in formalin for histopathology. The results demonstrated that ASEE displayed a protective effect on liver function tests (LFT), renal function tests (RFT), and lipid biomarkers in comparison to the CCl4 group. The histological data also unveiled a substantial safeguarding impact on liver damage, characterized by a reduction in apoptosis, diminished liver hemorrhage, and decreased accumulation of cellular debris. The data indicates that ethanolic extract from almond shells possesses hepatoprotective potential, suggesting its viability as an alternative source for hepatoprotective drug development after pre-clinical research.

Identification of Novel Natural Inhibitors to Human 3-Phosphoglycerate Dehydrogenase (PHGDH) for Cancer Treatment.

Targeting the serine biosynthesis pathway enzymes has turned up as a novel strategy for anti-cancer therapeutics. 3- Phosphoglycerate dehydrogenase (PHGDH) is the rate-limiting enzyme that catalyzes the conversion of 3-Phosphoglyceric acid (3-PG) into 3-Phosphohydroxy pyruvate (3-PPyr) in the first step of serine synthesis pathway and perform a critical role in cancer progression. PHGDH has been reported to be overexpressed in different types of cancers and emerged as a novel target for cancer therapeutics. During this study, virtual screening tools were used for the identification of inhibitors of PHGDH. A library of phenolic compounds was docked against two binding sites of PHGDH using Molegro Virtual Docker (MVD) software. Out of 169 virtually tested compounds, Salvianolic acid C and Schizotenuin F possess good binding potential to co-factor binding site of PHGDH while Salvianolic acid I and Chicoric acid were identified as the best binding compounds toward the substrate binding site of PHGDH. The top selected compounds were evaluated for different physiochemical and ADMET properties, the obtained results showed that none of these hit compounds violated the Pfizer Rule and they possess acceptable ADMET profiles. Further, a commercially available hit compound, Chicoric acid, was evaluated for its anti-cancer potential against PHGDH-expressing gastric cancer cell lines (MGC-803 and SGC-7901) as well as cell lines with low expression of PHGDH (MCF-7 and MDA-MB2-31), which demonstrated that Chicoric acid possesses selective cytotoxicity toward PHGDH expressing cancer cell lines. Thus, this study has unveiled the potential of phenolic compounds, which could serve as novel candidates for the development of PHGDH inhibitors as anti-cancer agents.

Mangifera indica Extracts as Novel PKM2 Inhibitors for Treatment of Triple Negative Breast Cancer.

Pyruvate kinase (PK), a key enzyme that determines glycolytic activity, has been known to support the metabolic phenotype of tumor cells, and specific pyruvate kinase isoform M2 (PKM2) has been reported to fulfill divergent biosynthetic and energetic requirements of cancerous cells. PKM2 is overexpressed in several cancer types and is an emerging drug target for cancer during recent years. Therefore, this study was carried out to identify PKM2 inhibitors from natural products for cancer treatment. Based on the objectives of this study, firstly, plant extract library was established. In order to purify protein for the establishment of enzymatic assay system, pET-28a-HmPKM2 plasmid was transformed to E. coli BL21 (DE3) cells for protein expression and purification. After the validation of enzymatic assay system, plant extract library was screened for the identification of inhibitors of PKM2 protein. Out of 51 plant extracts screened, four extracts Mangifera indica (leaf, seed, and bark) and Bombex ceiba bark extracts were found to be inhibitors of PKM2. In the current study, M. indica (leaf, seed, and bark) extracts were further evaluated dose dependently against PKM2. These extracts showed different degrees of concentration-dependent inhibition against PKM2 at 90-360 µg/ml concentrations. We have also investigated the anticancer potential of these extracts against MDA-MB231 cells and generated dose-response curves for the evaluation of IC50 values. M. indica (bark and seed) extracts significantly halted the growth of MDA-MB231 cells with IC50 values of 108 µg/ml and 33 µg/ml, respectively. Literature-based phytochemical analysis of M. indica was carried out, and M. indica-derived 94 compounds were docked against three binding sites of PKM2 for the identification of PKM2 inhibitors. The results of in silico based screening have unveiled various PKM2 modulators; however, further studies are recommended to validate their PKM2 inhibitory potential via in vitro biochemical assay. The results of this study provide novel findings for possible mechanism of action of M. indica (bark and seed) extracts against TNBC via PKM2 inhibition suggesting that M. indica might be of therapeutic interest for the treatment of TNBC.