Antidiabetic drug Jardiance (Empagliflozin) effectively attenuated the weight gain induced by the antipsychotic drug Zyprexa (Olanzapine) in female Wistar rats

Atypical antipsychotic drugs are commonly associated with undesirable side effects including body weight gain (BWG) and metabolic deficits. Many pharmacological interventions have been tested to minimize or prevent these side effects. Preliminary evidence suggested that antidiabetic drugs may be effective in attenuating the BWG induced by antipsychotic drugs. In the first phase, we carried out a 28-day study to standardize the correlated effective dosage of the antidiabetic drug empagliflozin (EMPA) and the antipsychotic drug olanzapine (Ola). Rats were divided into control (vehicle), Ola-4 and Ola-8 (4 and 8 mg/kg/OD, IP, respectively), and EMPA-10 and EMPA-20 (10 and 20 mg/kg/OD, IG, respectively) groups. Both doses of Ola produced a significant increase in the percentage of BWG, however, Ola-4 produced a higher BWG. Also, both the doses of EMPA were able to reverse the effect of Ola-induced BWG; however, EMPA-20 produced a higher reversal in BWG and normalized the rat\u27s body weight. So, we concluded that Ola-4 and EMPA-20 were the most effective dosage for experimental purposes in female Wistar rats. In the second phase of the study, we examined the effect of EMPA-20 on BWG induced by Ola-4 in female as well as male Wistar rats. Rats were divided into six groups based on the dosage they received: group 1 (female control), group 2 (female EMPA-20), group 3 (female Ola-4), group 4 (female Ola-4 + EMPA-20), group 5 (male control), and group 6 (male Ola-4). Ola induced sustained increase in BWG. The subsequent treatment of Group 3 and 4 with EMPA attenuated the Ola-induced BWG in female Wistar rats. In terms of the gender difference, the male control group 5 and male Ola group 6 gained more weight throughout the study as compared to the female control group 1 and female Ola group 3, respectively. However, Ola did not cause any weight difference between male rats treated with Ola in comparison with male control group, thus showing a significant gender difference regarding body weight between male and female Wistar rats regardless of Ola administration. In addition, the present findings showed that EMPA effectively attenuated the Ola-induced BWG in female Wistar rats. These novel findings should help to better understand the underlying molecular and behavioral mechanisms contributing to the observed increase in body weight after treatment

Studies on the role of goat heart galectin-1 as an erythrocyte membrane perturbing agent

AbstractGalectins are β-galactoside binding lectins with a potential hemolytic role on erythrocyte membrane integrity and permeability. In the present study, goat heart galectin-1 (GHG-1) was purified and investigated for its hemolytic actions on erythrocyte membrane. When exposed to various saccharides, lactose and sucrose provided maximum protection against hemolysis, while glucose and galactose provided lesser protection against hemolysis. GHG-1 agglutinated erythrocytes were found to be significantly hemolyzed in comparison with unagglutinated erythrocytes. A concentration dependent rise in the hemolysis of trypsinized rabbit erythrocytes was observed in the presence of GHG-1. Similarly, a temperature dependent gradual increase in percent hemolysis was observed in GHG-1 agglutinated erythrocytes as compared to negligible hemolysis in unagglutinated cells. The hemolysis of GHG-1 treated erythrocytes showed a sharp rise with the increasing pH up to 7.5 which became constant till pH 9.5. The extent of erythrocyte hemolysis increased with the increase in the incubation period, with maximum hemolysis after 5h of incubation. The results of this study establish the ability of galectins as a potential hemolytic agent of erythrocyte membrane, which in turn opens an interesting avenue in the field of proteomics and glycobiology

Analyzing the Impact of Soft, Stimulating and Depressing Songs on Attention Among Undergraduate Students: A Cross-Sectional Pilot Study in Bangladesh

Music is strongly linked to attention and giving attention can boost intelligence. The purpose of this study was to scrutinize the impact of soft, stimulating, and depressing songs on the attention of students. The study was performed on 280 undergraduate students. Students were divided into 4 groups (i.e., control, soft, stimulating, and depressing) and subjected to 3 songs, soft (That’s My Name), stimulating (Rain Over Me) and depressing (Broken Angel) songs. The Uddin’s Numeral Finding (NF) and Typo Revealing (TR) tests were used to analyze the attention of the students. In the NF, 75.54% attention was exerted by students subjected to stimulating song followed by soft song’s group (i.e., 74.32%) with respect to control group. Amid all groups, the lowest percentage, 70.77% of attention was reported for students subjected to the depressing song. For TR test, stimulating song’s group exerted highest, 45.97% attention, soft song’s group exerted 45.27%, control group exerted 42.70%, and lowest (i.e., 41.54%) attention was exerted by depressing song’s group. In NF test, concerning sex, amid male and female, male exerted higher (77.04%) attention than female but for TR test female exerted higher (i.e., 48.15%) attention for students subjected to stimulating song. Regarding the age of the study in case of NF test for stimulating song’s group, 18–20 years age students exerted highest, 82.07% attention but for TR test highest, 48.75% attention was reported for 23–25 years age students. For NF test, regarding the age of the study 1st-year student exerted highest, 92.44% attention but for TR test highest, 57.33% attention was reported for 3rd-year students for stimulating song’s group. Concerning residential status in both NF and TR tests, for students lived with family subjected to stimulating song exerted highest, 77.93% and 48.6% attention, respectively with respect to students lived without family and remaining groups. This study suggested that song influences the neuronal circuits linked to alert and cognitive functions and the stimulating song has the acme power of increasing attention while depressing song reduces the attention. Therefore, the exciting song can be an operative intervention for enhancing attention, cognitive functions, and treatment of associated neuropsychological disorders

Naringenin as a potent inhibitor molecule for targeting microtubule affinity-regulating kinase 4 (mark4): a molecular docking and in vitro study for therapeutics of Alzheimer's disease

Background: The targeted inhibition of Microtubule Affinity-Regulating Kinase 4 (MARK4) using small molecule inhibitors has emerged as a promising therapeutic approach for diverse diseases, including neurological disorders such as Alzheimer’s disease. Ongoing research endeavors aim to develop novel and more effective MARK4 inhibitors with enhanced target specificity and reduced off-target effects. In the present study, we sought to investigate the binding affinity and impact of Naringenin on the activity of MARK4. Methods: We employed a combination of molecular docking and other bioinformatics methods, a fluorescence-based inhibition assay, as well as a kinase activity assay to assess the binding affinity and inhibition potential of Naringenin against MARK4. Additionally, we utilized the MTT assay to examine the effect of Naringenin on the viability of two cell lines: the normal human cell line HEK-293 and the neuronal cell line SH-SY5Y. The IC50 dose of Naringenin, determined from the MTT assay, provided a valuable reference point for subsequent neuronal cell line experiments.Results: The results of the molecular docking demonstrated a robust binding affinity of Naringenin (-7.8 kcal/mol) to MARK4, affirming its potency as an inhibitor. Moreover, the fluorescence inhibition and kinase activity assays confirmed the inhibitory effect of Naringenin on MARK4. Interestingly, the MTT assay outcomes indicated that increasing concentrations of Naringenin did not significantly impact the viability of HEK 293 cells, while exhibiting a pronounced effect on SH-SY5Y neuronal cells. The IC50 concentration of Naringenin was determined to be 10.0 ± 1.33 μM for SH-SY5Y neuronal cells.Conclusion: In conclusion, this study reported Naringenin as a potential inhibitor molecule for MARK4, offering promising prospects for future therapeutic interventions in neuronal disorders specifically for Alzheimer’s disease.Keywords: Inhibition; Microtubule Affinity-Regulating Kinase 4 (MARK4); Molecular docking; Naringenin; Neuronal disorders  Editorial Note: You are viewing the latest version of this manuscript having correction in abstract section, which is different from the originally published copy

Potential Therapeutic Implications of Caffeic Acid in Cancer Signaling: Past, Present, and Future

Caffeic acid (CA) has been present in many herbs, vegetables, and fruits. CA is a bioactive compound and exhibits various health advantages that are linked with its anti-oxidant functions and implicated in the therapy and prevention of disease progression of inflammatory diseases and cancer. The anti-tumor action of CA is attributed to its prooxidant and anti-oxidant properties. CA’s mechanism of action involves preventing reactive oxygen species formation, diminishing the angiogenesis of cancer cells, enhancing the tumor cells’ DNA oxidation, and repressing MMP-2 and MMP-9. CA and its derivatives have been reported to exhibit anti-carcinogenic properties against many cancer types. CA has indicated low intestinal absorption, low oral bioavailability in rats, and pitiable permeability across Caco-2 cells. In the present review, we have illustrated CA’s therapeutic potential, pharmacokinetics, and characteristics. The pharmacological effects of CA, the emphasis on in vitro and in vivo studies, and the existing challenges and prospects of CA for cancer treatment and prevention are discussed in this review

Big data acquired by Internet of Things-enabled industrial multichannel wireless sensors networks for active monitoring and control in the smart grid industry 4.0

Smart Grid Industry 4.0 (SGI4.0) defines a new paradigm to provide high-quality electricity at a low cost by reacting quickly and effectively to changing energy demands in the highly volatile global markets. However, in SGI4.0, the reliable and efficient gathering and transmission of the observed information from the Internet of Things (IoT)-enabled Cyber-physical systems, such as sensors located in remote places to the control center is the biggest challenge for the Industrial Multichannel Wireless Sensors Networks (IMWSNs). This is due to the harsh nature of the smart grid environment that causes high noise, signal fading, multipath effects, heat, and electromagnetic interference, which reduces the transmission quality and trigger errors in the IMWSNs. Thus, an efficient monitoring and real-time control of unexpected changes in the power generation and distribution processes is essential to guarantee the quality of service (QoS) requirements in the smart grid. In this context, this paper describes the dataset contains measurements acquired by the IMWSNs during events monitoring and control in the smart grid. This work provides an updated detail comparison of our proposed work, including channel detection, channel assignment, and packets forwarding algorithms, collectively called CARP [1] with existing G-RPL [2] and EQSHC [3] schemes in the smart grid. The experimental outcomes show that the dataset and is useful for the design, development, testing, and validation of algorithms for real-time events monitoring and control applications in the smart grid

Role of anti-diabetic drugs as therapeutic agents in Alzheimer's disease

Recent data have suggested a strong possible link between Type 2 Diabetes Mellitus and Alzheimer’s disease (AD), although exact mechanisms linking the two are still a matter of research and debate. Interestingly, both are diseases with high incidence and prevalence in later years of life. The link appears so strong that some scientists use Alzheimer’s and Type 3 Diabetes interchangeably. In depth study of recent data suggests that the anti diabetic drugs not only have possible role in treatment of Alzheimer’s but may also arrest the declining cognitive functions associated with it. The present review gives an insight into the possible links, existing therapeutics and clinical trials of anti diabetic drugs in patients suffering from AD primarily or as co-morbidity. It may be concluded that the possible beneficial effects and usefulness of the current anti diabetic drugs in AD cannot be neglected and further research is required to achieve positive results. Currently, several drug trials are in progress to give conclusive evidence based data

Therapeutic effect of combination vitamin D3 and siponimod on remyelination and modulate microglia activation in cuprizone mouse model of multiple sclerosis

Stimulation of remyelination is critical for the treatment of multiple sclerosis (MS) to alleviate symptoms and protect the myelin sheath from further damage. The current study aimed to investigate the possible therapeutic effects of combining vitamin D3 (Vit D3) and siponimod (Sipo) on enhancing remyelination and modulating microglia phenotypes in the cuprizone (CPZ) demyelination mouse model. The study was divided into two stages; demyelination (first 5 weeks) and remyelination (last 4 weeks). In the first 5 weeks, 85 mice were randomly divided into two groups, control (n = 20, standard rodent chow) and CPZ (n = 65, 0.3% CPZ mixed with chow for 6 weeks, followed by 3 weeks of standard rodent chow). At week 5, the CPZ group was re-divided into four groups (n = 14) for remyelination stages; untreated CPZ (0.2 ml of CMC orally), CPZ+Vit D3 (800 IU/kg Vit D3 orally), CPZ+Sipo (1.5 mg/kg Sipo orally), and CPZ+Vit D3 (800 IU/kg Vit D3) + Sipo (1.5 mg/kg Sipo orally). Various behavioral tasks were performed to evaluate motor performance. Luxol Fast Blue (LFB) staining, the expression level of myelin basic protein (MBP), and M1/M2 microglia phenotype genes were assessed in the corpus callosum (CC). The results showed that the combination of Vit D3 and Sipo improved behavioral deficits, significantly promoted remyelination, and modulated expression levels of microglia phenotype genes in the CC at early and late remyelination stages. These results demonstrate for the first time that a combination of Vit D3 and Sipo can improve the remyelination process in the cuprizone (CPZ) mouse model by attenuating the M1 microglia phenotype. This may help to improve the treatment of MS patients

Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019

BACKGROUND: The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. METHODS: We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. FINDINGS: In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. INTERPRETATION: The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. FUNDING: The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38)