Retraction notice to "Mechanistic insight into the bioactivity of prodigiosin-entrapped lipid nanoparticles against triple-negative breast, lung and colon cancer cell lines" [Heliyon 9 (2023) e16963].

[This retracts the article DOI: 10.1016/j.heliyon.2023.e16963.].

Mechanistic insight into the bioactivity of prodigiosin-entrapped lipid nanoparticles against triple-negative breast, lung and colon cancer cell lines.

This research investigates the potentials of prodigiosin(PG) derived from bacteria and its formulations against triple-negative breast (TNB), lung, and colon cancer cells. The PG was extracted from S. marcescens using continuous batch culture, characterized, and formulated into lyophilized parenteral nanoparticles (PNPs). The formulations were characterized with respect to entrapment efficiency (EE), DSC, FT-IR, TEM, and proton nuclear magnetic resonance (1H NMR) spectroscopy. In vitro drug release was evaluated in phosphate buffer (pH 7.4) while acute toxicity, hematological and histopathological studies were performed on rats. The in vitro cytotoxicity was evaluated against TNB (MCF-7), lung (A-549), and colon (HT-29) cancer cell lines. High EE (92.3 ± 12%) and drug release of up to 89.4% within 8 h were obtained. DSC thermograms of PG and PG-PNPs showed endothermic peaks indicating amorphous nature. The FT-IR spectrum of PG-PNPs revealed remarkable peaks of pure PG, indicating no strong chemical interaction between the drug and excipients. The TEM micrograph of the PG-PNPs showed nano-sized formulations (20-30 nm) whose particles were mostly lamellar and hexagonal structures. The 1H NMR result revealed the chemical structure of PG showing all assigned proton chemical shifts. Toxicity results of the PG and its formulation up to a concentration of 5000 mg/kg showed insignificant vacuolar changes of hepatocytes in the liver, with normal renal medulla and cortex in the kidney. The PG and PG-PNPs inhibited the growth of breast, lung, and colon cell lines. The nano-sized lipid formulation (PG-PNPs) showed potential in PG delivery and cancer treatments.

Safety and Protective Effects of Influenza Vaccination in Pregnant Women on Pregnancy and Birth Outcomes in Pune, India: A Cross-Sectional Study.

BACKGROUND: Maternal influenza vaccination provides effective protection against influenza infections in pregnant women and their newborns. In India, the influenza vaccine has not yet been offered through immunization programs, owing to the lack of sufficient safety data for pregnant Indian women. METHODS: This cross-sectional observational study enrolled 558 women admitted to the obstetrics ward of a civic hospital in Pune. Study-related information was obtained from the participants through hospital records and interviews using structured questionnaires. Univariate and multivariable analysis was used, and the chi-square test with adjusted odds ratio was estimated to account for vaccine exposure and the temporal nature of each outcome, respectively. RESULTS: Women not vaccinated against influenza during pregnancy had a higher risk of delivering very LBW infants, and possible protective effects were suggested (AOR 2.29, 95% CI 1.03 to 5.58, p = 0.03). No association was observed between maternal influenza vaccination for Caesarean section (LSCS) (AOR 0.97, 95% CI, 0.78, 1.85), stillbirth (AOR 1.8, 95% CI 0.18, 24.64) and NICU admission (AOR, 0.87, 0.29 to 2.85), and congenital anomaly (AOR, 0.81, 0.10 to 3.87). INTERPRETATION: These results show that the influenza vaccine administered during pregnancy is safe and might lower the risk of negative birth outcomes.

Improvement of cognitive dysfunction by a novel phosphodiesterase type 5 inhibitor, Tadalafil.

There is substantial evidence for the modulatory role of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterases (PDEs) in memory and synaptic plasticity, and an increase in intracellular cGMP facilitates these processes. The present study was aimed at the neuropharmacological investigations of tadalafil (TAD 5, 10, and 20 mg/kg, p.o.) and further involvement of nitric oxide (NO)-cGMP in its effects. The effects of tadalafil and its combination with NG -nitro-L-arginine methyl ester (L-NAME) were investigated in scopolamine- and diabetes-induced cognitive dysfunction using elevated plus maze (EPM) and object recognition (ORT) tests. The results of EPM revealed that the scopolamine- and diabetes-induced learning and memory deficit was dose dependently attenuated after administration of TAD (TAD 10 and 20 mg/kg, p.o.) in both paradigms studied. Administration of L-NAME (20 mg/kg) aggravated scopolamine- and diabetes-induced learning and memory deficit. Co-administration of L-NAME (20 mg/kg) after TAD (20 mg/kg) produced significant increase in cognitive performance as compared to scopolamine- and diabetic- control group. This showed that L-NAME (20 mg/kg) aggravated scopolamine- and diabetes-induced learning and memory deficit was significantly reversed by TAD (20 mg/kg). The results of the present study revealed that tadalafil by inhibiting PDE5 possibly elevated the cGMP level that through a diversity of its substrates produced neuropharmacological effects in cognitive dysfunction.

Alzheimer's Disease: Pathogenesis and Therapeutic Interventions.

BACKGROUND: Alzheimer's Disease (AD) is the most common cause of dementia. Genetics, excessive exposure to environmental pollutants, as well as unhealthy lifestyle practices are often linked to the development of AD. No therapeutic approach has achieved complete success in treating AD; however, early detection and management with appropriate drugs are key to improving prognosis. INTERVENTIONS: The pathogenesis of AD was extensively discussed in order to understand the reasons for the interventions suggested. The interventions reviewed include the use of different therapeutic agents and approaches, gene therapy, adherence to healthy dietary plans (Mediterranean diet, Okinawan diet and MIND diet), as well as the use of medicinal plants. The potential of nanotechnology as a multidisciplinary and interdisciplinary approach in the design of nano-formulations of AD drugs and the use of Superparamagnetic Iron Oxide Nanoparticles (SPIONs) as theranostic tools for early detection of Alzheimer's disease were also discussed.

Ameliorative Effect of Chronic Supplementation of Protocatechuic Acid Alone and in Combination with Ascorbic Acid in Aniline Hydrochloride Induced Spleen Toxicity in Rats.

Background. Present study was designed to evaluate the protective effects of protocatechuic acid alone and in combination with ascorbic acid in aniline hydrochloride induced spleen toxicity in rats. Materials and Methods. Male Wistar rats of either sex (200-250 g) were used and divided into different groups. Spleen toxicity was induced by aniline hydrochloride (100 ppm) in drinking water for a period of 28 days. Treatment group received protocatechuic acid (40 mg/kg/day, p.o.), ascorbic acid (40 mg/kg/day, p.o.), and combination of protocatechuic acid (20 mg/kg/day, p.o.) and ascorbic acid (20 mg/kg/day, p.o.) followed by aniline hydrochloride. At the end of treatment period serum and tissue parameters were evaluated. Result. Rats supplemented with aniline hydrochloride showed a significant alteration in body weight, spleen weight, feed consumption, water intake, hematological parameters (haemoglobin content, red blood cells, white blood cells, and total iron content), tissue parameters (lipid peroxidation, reduced glutathione, and nitric oxide content), and membrane bound phosphatase (ATPase) compared to control group. Histopathology of aniline hydrochloride induced spleen showed significant damage compared to control rats. Treatment with protocatechuic acid along with ascorbic acid showed better protection as compared to protocatechuic acid or ascorbic acid alone in aniline hydrochloride induced spleen toxicity. Conclusion. Treatment with protocatechuic acid and ascorbic acid in combination showed significant protection in aniline hydrochloride induced splenic toxicity in rats.

Design, synthesis and molecular modeling studies of few chalcone analogues of benzimidazole for epidermal growth factor receptor inhibitor in search of useful anticancer agent.

In the present investigation, few 3-(substitutedphenyl)-1-[2-(1-hydroxy-ethyl)]-1H-benzimidazol-1-yl)prop-2-en-1-ones are EGFR antagonist are designed, by molecular docking analysis. The synthesized compounds were tested for their in vitro anticancer activity by propidium iodide fluorescent assay and Trypan blue viability assay against colorectal cancer cell lines (HCT116) and non-small cell lung cancer cell lines (H460). Human Epithelial Kidney cell lines (HEK) are used as normal cell lines for studying effect of drug on non-cancerous cells within human body. Evaluation of cytotoxic studies of synthesized compounds CHL(1-8) reveal that compound CHL1 [IC50=7.31 and 10.16 µM against HCT116 and H460 cell lines respectively, by PI assay] and CHL8 [IC50=12.52 and 6.83 against HCT116 and H460µM cell lines respectively] possess promising cytotoxic activity.

Therapeutic potential of metabotropic glutamate receptor 4-positive allosteric modulator TAS-4 in rodent models of movement disorders.

Parkinson's disease (PD) is a very serious neurological disorder, and current methods of treatment fail to achieve long-term control. Previous studies suggest that stimulation of the metabotropic glutamate receptor 4 (mGluR4) represents a promising new approach to the symptomatic treatment of Parkinson's disease (PD). Preclinical models using both agonists and positive allosteric modulators of mGluR4 have demonstrated the potential for this receptor for the treatment of PD. In the present study, we describe the pharmacological characterization of an mGluR4 PAM, N-(2, 4-dichlorophenyl) pyridine-2-carboxamide (TAS-4), in several rodent PD models. TAS-4 is a potent and selective mGluR4 PAM of the human mGluR4 receptor (EC50- 287.8nM). TAS-4 showed efficacy alone or when administered in combination with l-DOPA. When administered alone, TAS-4 exhibited efficacy in reversing haloperidol-induced catalepsy. In addition, acute TAS-4 dose-dependently potentiated contralateral turning behavior induced by a threshold dose of l-3,4-dihydroxyphenylalanine (l-DOPA, 4mg/kg i.p.), a classical test for antiparkinson drug screening. Subchronic (28days, twice a day) TAS-4 (10mg/kg i.p.)+l-DOPA (4mg/kg i.p.) did not induce sensitization to turning behavior or abnormal involuntary movements during the course of treatment. Moreover, subchronic administration of a fully effective dose of l-DOPA (8mg/kg i.p.) significantly induces sensitization to turning behavior or abnormal involuntary movements. Results showed that TAS-4, in association with a low dose of l-DOPA, displayed antiparkinsonian activity similar to that produced by a full dose of l-DOPA without exacerbating abnormal motor side effects.

Protective effects of dioscorea alata L. In aniline exposure-induced spleen toxicity in rats: a biochemical study.

INTRODUCTION: Present study was designed to evaluate the protective effects of ethanolic extract of Dioscorea alata L. (DA) on hematological and biochemical changes in aniline-induced spleen toxicity in rats. MATERIALS AND METHODS: Wistar rats of either sex (200-250g) were used in the study and each group contains six rats. Splenic toxicity was induced in rats by administration of aniline hydrochloride (AH; 100 ppm) in drinking water for a period of 30 days. Treatment groups received DA (50 and 100 mg/kg/day, po) along with AH. At the end of treatment period, various serum and tissue parameters were evaluated. RESULT: Rats administered with AH (100 ppm) in drinking water for 30 days showed a significant alteration in general parameters (organ weight, body weight, water intake, feed consumption, and fecal matter content), hematological parameters (red blood cell (RBC), white blood cell (WBC), and hemoglobin content), and biochemical parameters (total iron content, lipid peroxidation, reduced glutathione (GSH), and nitric oxide (NO) content) of spleen. Treatment with DA (50 and 100 mg/kg/day, po) for 30 days along with AH showed significant recovery in aniline-induced splenic toxicity. CONCLUSION: The present result showed that involvement of oxidative and nitrosative stress in aniline-induced splenic toxicity and DA protects the rats from the toxicity, which might be due to its antioxidant property and the presence of different phytochemicals.

NS-1: a novel partial peroxisome proliferator-activated receptor γ agonist to improve insulin sensitivity and metabolic profile.

Peroxisome proliferator-activated receptor (PPAR) γ is known to be a key regulator of insulin resistance. We characterized the pharmacological profiles of NS-1 chemically known as (5Z)-5-[4-hydroxy-3-methoxy-phenyl) methylene] thiazolidine-2, 4-dione), as a selective partial activator of PPARγ. In transient transactivation assay in NIH3T3 cells, NS-1 showed a partial activation against human PPARγ with an EC (50) of 0.91 µM without activating human PPARα and PPARδ. In adipocyte differentiation assay, NS-1 induced adipocyte differentiation, which was ~25-fold weaker inducer of GPDH activities than pioglitazone and also showed weak adipogenic activity in C3H10T1/2 pluripotent stem cells using Oil Red O staining. NS-1 showed good in vivo pharmacokinetic profiles in C57BL/6J mice at 30 mg/kg oral dose with Cmax-26 µM, terminal elimination half-life- 2.5h and bioavailability of 85%. Furthermore, NS-1 significantly improved hyperglycemia and insulin resistance in DIO animals when orally administered at a dose of 30 mg/kg/day for 45 days without significant weight gain. Overall, these studies suggest that NS-1 improves insulin resistance in such animal models through activation of PPARγ-mediated transcriptional activity and that it would be a new therapeutic candidate with potential for the treatment of type 2 diabetic patients.

Protective effect of aqueous extract of Spinacia oleracea leaves in experimental paradigms of inflammatory bowel disease.

The present study was aimed to assess the protective effect of aqueous extract of Spinacia oleracea leaves (AESO 250, 500, and 1,000 mg/kg, p.o.) in inflammatory bowel disease using acetic acid- and ethanol-induced colitis in mice and indomethacin-induced enterocolitis in rats. The preliminary phytochemical analysis and further high performance thin layer chromatographic (HPTLC) analysis and phytochemical tests of HPTLC bands confirmed the presence of flavonoids and tannins in AESO. In acute oral toxicity study, administration of AESO (5,000 mg/kg, p.o.) did not show any sign of toxicity and mortality. The treatment with AESO significantly increased body weight, decreased diarrhea with bloody stools, increased blood hemoglobin and plasma total protein, and decreased serum and ileum or colon malondialdehyde content and attenuated the extent of lesions and ameliorated the histological injury of mucosa in all paradigms. The most prominent effects were evident for AESO 1,000 mg/kg. The results of the present study revealed that AESO was effective in attenuating almost all the symptoms of IBD in experimental paradigms. The effect might be due to the antioxidant activity of the flavonoids present in the AESO.

Synthesis, biological screening and molecular modeling studies of novel 3-chloro-4-substituted-1-(2-(1H-benzimidazol-2-yl)phenyl))-azetidin-2-ones.

In the present investigation synthesis of some novel 1-(2-(1H-benzimidazol-2-yl)phenyl)-3-chloro-4-(Un/substitutedphenyl)azetidin-2-one (3a-3h) antibacterial are reported. Structures of synthesized compounds were confirmed by spectral techniques (IR, Mass, (1)H-NMR) All reactions were monitored with analytical thin layer chromatography. Synthesized compounds were docked in to the active site of enzyme transpeptidase. Compounds 3a, 3b, 3d and 3g were found to have good affinity for transpeptidase with potent antibacterial activity. A good correlation is found between in silico docking analysis and in vitro antibacterial activity.

Screening of Ficus religiosa leaves fractions for analgesic and anti-inflammatory activities.

OBJECTIVE: To evaluate the different fractions of dried leaves of Ficus religiosa Linn for analgesic and anti-inflammatory activity using different models of pain and inflammation MATERIALS AND METHODS: The analgesic activity of F. religiosa carried out using acetic acid-induced writhing in mice and tail flick test in rats. The anti-inflammatory activity was evaluated using carrageenan-induced rat paw edema and cotton pellet-granuloma formation in rats. Five different fractions (FRI, FRII, FRIII, FRIV and FRV) of F. religiosa at the dose level of 20 and 40 mg/kg, p.o were tested. RESULTS: The fraction FRI (40 mg/kg, p.o.) and FRIII (40 mg/kg, p.o) were found to be more effective (P<0.01) in preventing carrageenan induced rat paw edema, cotton pellet granuloma formation, and acetic acid induced writhing compared to the other fractions. FRI (20 mg/kg, p.o.) and FRIII (20 mg/kg, p.o.) were also found to be more effective in increasing latency period in tail flick method. CONCLUSION: Out of five different fractions of F. religiosa leaves tested, FRI and FRIII possess potent analgesic and anti-inflammatory activities against different models of inflammation and pain.

Synthesis and molecular modeling studies of 3-chloro-4-substituted-1-(8-hydroxy-quinolin-5-yl)-azetidin-2-ones as novel anti-filarial agents.

A series of 3-chloro-4-substituted-1-(8-hydroxy-quinolin-5-yl)-azetidin-2-ones were synthesized and evaluated for their in vitro anti-filarial activity. To pre-assess the anti-filarial behavior of synthesized compounds (V(a-f)) on a structural basis, automated docking studies were carried out with Molecular Design Suite (MDS v 3.5) into the active site of glutathione-S-transferase (GST) enzyme; scoring functions of these compounds at the active site of the GST enzyme were used for correlation with observed activity. Compounds V(e) and V(f) have shown good affinity for receptor GST, as well as in vitro anti-filarial potency.