ANTIHYPERGLYCAEMIC AND ANTINOCICEPTIVE ACTIVITY EVALUATION OF METHANOLIC EXTRACT OF WHOLE PLANT OF AMARANTHUS TRICOLOUR L. (AMARANTHACEAE)

Amaranthus tricolor whole plants are used by folk medicinal practitioners of Bangladesh for treatment of pain, anaemia, dysentery, skin diseases, diabetes, and as a blood purifier. Thus far, no scientific studies have evaluated the antihyperglycaemic and antinociceptive effects of the plant. The present study was carried out to evaluate the possible glucose tolerance efficacy of methanolic extracts of A. tricolour whole plants using glucose-induced hyperglycaemic mice, and antinociceptive effects with acetic acid-induced gastric pain models in mice. In antihyperglycaemic activity tests, the extract at different doses was administered one hour prior to glucose administration and blood glucose level was measured after two hours of glucose administration (p.o.) using glucose oxidase method. The statistical data indicated the significant oral hypoglycaemic activity on glucose-loaded mice at all doses of the extracts tested. Maximum antihyperglycaemic activity was shown at 400 mg extract per kg body weight, which was comparable to that of a standard drug, glibenclamide (10 mg/kg body weight). In antinociceptive activity tests, the extract also demonstrated a dose-dependent significant reduction in the number of writhings induced in mice through intraperitoneal administration of acetic acid. Maximum antinociceptive activity was observed at a dose of 400 mg extract per kg body weight, which compared favourably with that of a standard antinociceptive drug, aspirin, when administered at a dose of 200 mg per kg body weight. The results validate the folk medicinal use of the plant for reduction of blood sugar in diabetic patients as well as the folk medicinal use for alleviation of pain. The results suggest that this plant may possess further potential for scientific studies leading to possible discovery of efficacious antihyperglycaemic and antinociceptive components

The role of MEK1/2 and MEK5 in melatonin-mediated actions on osteoblasts and osteoclasts differentiation, bone formation, bone microarchitecture, and bone biomechanics

Melatonin, the main endogenous hormone to entrain the circadian system, is not limited to its role in regulating the sleep-wake cycle; rather, it affects a wide variety of systems involving antioxidant, anti-inflammation, blood pressure regulation, seasonal reproduction, ovarian physiology, and immune function. Driven by the diversity of its action, melatonin for a long time has also been studied in the field of bone and mineral research both clinically and pre-clinically. Exogenous administration of melatonin in clinical trials in perimenopausal women (MOPS; NCT01152580); or postmenopausal women with osteopenia (MelaOST; NCT01690000 and MOTS; NCT01870115) confirmed improvement of bone mineral density (BMD) (MelaOST; MOTS) and bone marker turnover status (MOPS, MOTS). Studies involving preclinical animal models also revealed melatonin’s effect in improving age-related bone loss and BMD with efficacy similar to a therapeutically relevant estrogen and progesterone hormone therapy. At the cellular level, this increase in BMD by melatonin was accompanied by increases in the levels of osteogenic proteins, pErk1/2, and pErk5, indicating the potential role of the MAPKs, MEK1/2/ERK1/2 and MEK5/ERK5 pathways in mediating melatonin’s action. To investigate this further, the goal of this project was to study the role of MEK1/2 and MEK5 in regulating melatonin-mediated osteoblast and osteoclast differentiation and function in vitro and in vivo and their role in modulating bone density, quality, strength, and formation. In vitro, using small-molecule inhibitors and a co-culture model of human bone marrow-derived mesenchymal stem cells (hMSCs) and peripheral blood monocytes (hPBMCs), it was discovered that melatonin’s stimulating effect on osteoblastogenesis is mediated through MT2 melatonin receptors, MEK1/2, MEK5, and perhaps PPARγ and GLUT4. To further confirm the involvement of MEK1/2 and MEK5 in melatonin’s effect, CRISPR/Cas9 knockout approaches were used to generate MEK1KO or MEK5KO hMSCs and mouse mesenchymal stem cells (mMSCs). Both monoculture and co-culture models were developed using these MEK1KO or MEK5KO MSCs with a goal to study the role of melatonin, melatonin receptors, MEK1/2, and MEK5 in osteoblast and osteoclast differentiation and communication between these cells. In both human and mouse MSCs, melatonin’s effect on osteoblastogenesis was occurring strictly through MT2R-mediated actions on MEK5 and/or MEK1 and not through an indirect action of melatonin on MEK5 or MEK1, consistent with the findings using small molecule inhibitors. In vivo and using small molecule inhibitors or a CRISPR/Cas9 knockout approach, it was further determined that Mek1/2 and 5 were primary drivers underlying melatonin’s actions on bone formation, bone microarchitecture, and bone biomechanics. In the small molecule inhibitor study where Balb(c) mice (female) were injected with melatonin in the absence or presence of selective MEK1/2, MEK5, or MEK1/2/5 inhibitors for 45 days, it was demonstrated that melatonin, through MEK1/2 and MEK5, increased osteogenic protein expression (Runx2, Bmp-2, Fra-1, Opg) and decreased metabolic protein, Pparγ expression; and also modulated bone microarchitecture (i.e., trabecular number, separation, and connectivity density) and bone mechanical properties (i.e., ultimate stress). A mouse calvarial defect model was developed using PLGA scaffolds seeded with mMSCs (wildtype, control, Mek1KO, Mek5KO) and placed into critical size calvarial defects created in Balb(c) mice (male and female) followed by treatment with vehicle or melatonin nightly for 90 days. This study demonstrated the involvement of Mek1 and Mek5 in new bone formation induced by melatonin in both genders supporting the findings in vitro in human and mouse MSCs. Gender-specific analyses of the calvarial data revealed unique gender differences in melatonin’s effect and kinase interaction with melatonin. These mechanisms of action demonstrating a unique role for Mek1/2 and Mek5 in mediating both osteogenic and metabolic pathways as well as demonstrating specificity of action in a gender-specific manner opens up new avenues of research examining conditions known to promote bone loss (i.e., diabetes, aging) in males and females and novel therapeutic strategies and agents to modulate bone loss to prevent fracture and mortality

Correction:Investigation of key performance indicators for performance management of the manufacturing industry in the era of the COVID-19 pandemic (Annals of Operations Research, (2023), 10.1007/s10479-023-05717-4)

Due to typesetting error article was published with missing affiliation of author Charbel Jose Chiappetta Jabbour and needs to be read as: Department of Information Systems, Supply Chain Management and Decision Support, NEOMA Business School, 1 rue du Maréchal Juin - BP 215, 76130 Mont-Saint-Aignan Cedex, France. Original article has been updated.</p

Investigation of key performance indicators for performance management of the manufacturing industry in the era of the COVID-19 pandemic

The execution of constructive Key Performance Indicators (KPIs) is a critical tool for the Performance Management (PM) of the manufacturing industry to regulate operations. The companies rely on the PM strategies grounded on conventional KPIs assessment to achieve sustainability although the current dynamic manufacturing environment is undergoing complexities. The KPIs used in the past for PM are not mutually dependent, as they have not been adequately measured and updated to address emergency situations like the COVID-19 pandemic, particularly for the Leather Products Industry (LPI). Monitoring of plentiful KPIs is inconceivable and literature is also not available. Realizing these gaps, this study accumulates suggestions from a wide-ranging context of 25 experts’ feedback. Initially, a set of KPI was identified through literature review and experts survey. Later, employing a Pareto analysis, 15 KPIs were identified from 48 KPIs. Then the finalized KPIs investigated utilizing linguistic Z-digits and Decision-Making Trial and Evaluation Laboratory (DEMATEL) to find the “Cause-Effect” relationship. An industrial chronology is conferred to demonstrate the potency and functionality of the suggested method. The upshot signifies the “Target fulfillment within the delivery time during COVID-19” as the most important KPI for the studied case. The outcomes will assist the LPI managers to dictate crucial KPIs suitably and flourish the PM in attaining the goals and objectives.</p

Effects of exposure to imidacloprid contaminated feed on the visceral organs of adult male rabbits (Oryctolagus cuniculus)

The best-known and often used systemic, broad-spectrum neonicotinoid pesticide is imidacloprid (IMI). This study was carried out on adult male rabbits (n = 12) to assess the residual effects of exposure to IMI-contaminated diet on the liver, lung, heart, and kidney. Pesticide-exposed rabbits (n = 6) received IMI contaminated green grass (Bildor® 0.5 ml (100 mg)/L water) every alternative day once daily for up to 15 days. The remaining rabbits were fed a standard diet free of pesticides as a control. During routine monitoring of the rabbits throughout the experiment, there were no apparent toxic symptoms identified. On days 16, after deep anesthesia blood and visceral organs were collected. The levels of hepatic serum aspartate transaminase and alanine transaminase were considerably elevated in IMI-exposed rabbits (p ≤ 0.05). Thin layer chromatography revealed that the residue of IMI was at the detectable level in the liver and stomach. Histopathologically, the liver revealed coagulation necrosis with granulomatous inflammation and congestion in portal areas with dilated and congested central veins. The lungs showed congestion of blood vessels and granulomatous inflammation around the terminal bronchiole. Accumulations of inflammatory cells were observed in the cortico-medullary junction in the kidney. The heart showed necrosis and infiltration of mononuclear cells within the cardiac muscles. The findings of the current study emphasize that IMI-contaminated feed exposure causes toxicity into the cellular level of different visceral organs of adult male rabbits and it may also cause the similar toxic effects of the other mammals specially the occupationally exposed persons

Chemically Converted Graphene as a Hole Transport Layer (HTL) Inorganic Photovoltaics (OPVS)

oai:ojs.pkp.sfu.ca:article/170Concerns about Global Warming and diminishing fossil fuel reserves have accelerated the search for low cost sources of renewable energy. Organic photovoltaics (OPVs) could be one such source; however, they have a list of shortcomings, including low efficiencies, short lifetimes, and reliance on poly (3, 4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS), an expensive and highly acidic (pH = 1) hole transport layer. Replacing PEDOT: PSS with chemically derived graphene may eliminate one of the drawbacks associated with OPVs. This paper took the first step towards that goal by developing a process to synthesize and characterize inverted and normal poly (3-hexylthiophene) (P3HT), [6, 6]-phenyl-C61 butyric acid methyl ester (PCBM) solar cells. Although detrimental to the stability of the cells, ambient synthesis replicated the conditions required for large-scale, industrial production. The utilization of graphene oxide (GO) thin films as the hole transport and electron blocking layer in organic photovoltaics (OPVs) is demonstrated. The incorporation of GO deposited from neutral solutions between the photoactive poly(3-hexylthiophene) (P3HT):phenyl-C61 butyric acid methyl ester (PCBM) layer and the transparent and conducting indium tin oxide (ITO) leads to a decrease in recombination of electrons and holes and leakage currents. This results in a dramatic increase in the OPV efficiencies to values that are comparable to devices fabricated with PEDOT: PSS as the hole transport layer. Our results indicate that GO could be a simple solution process able Alternative to PEDOT: PSS as the effective hole transport and electron blocking layer in OPV and light-emitting diode devices