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Water erosion is a major problem in the semi-arid environments of Algeria. In this vein, the objective of this study is to use the Revised Universal Soil Loss Equation (RUSLE) on the watershed of Medjerda which is located at the extreme of the North-Eastern part of the Algerian territory. Based on the crossing of various factors in raster mode under ArcGIS allows the production of diverse thematic maps corresponding to multiple factors: erosivity of precipitations, erodibility of soils, topography, the vegetal cover and the anti-erosive practices. Moreover, the risks’ map of water soil erosion was obtained depending on the combination of the previous thematic maps with four class risks has been made up indicating an average erosion value of 2.68 t/ha/year. However, this value is relatively reasonable in relation to the given rate by the interpretation of the bathymetric measures carried out in the Ain Dalia dam.

Water losses due to leakage are a pernicious problem for water utilities. Understanding and quantifying Non-Revenue Water (NRW) and water loss components is the first step in the management of urban water losses. Hydraulic modeling is a powerful tool to predict the impacts of different management scenarios on the hydraulics of the Water Distribution Network (WDN). The water distribution network (WDN) can be divided into a number of District Meter Areas (DMAs) with suitable sizes in order to apply pressure management. In this study, the Fixed Area Variable Area Discharge (FAVAD) concept and the number of leaks were analyzed for a number of water network pressure management areas in the city of Bendjerrah – the district of Guelma, Algeria. The analysis identified some anomalies concerning the parameters of some networks; especially those related to leakage exponent N1 values greater than 1.5. The approach used in this framework is based on the estimation of the leakage from the Minimum Night Flow (MNF) and the burst frequency of Average Zonal Pressure (AZP). After the use of this approach and the calibration procedure using the Epanet-calibrator on real District Meter Areas, the obtained results are very close to the real state of the network. In addition, this paper studies the possibility of explicitly incorporating the variation of the leakage zone in the hydraulic modeling of the water distribution systems. The results show that the power equation leakage exponent N1 estimates the total system leakage with an error of up to 20%. From the Minimum Night Flow, obtained by using the South African Night Flow (SANFLOW) practical tool, it was found that the actual losses calculated for sectors 1, 2, and 3 are respectively 25%, 45%, and 30%.

The clinical use of 5-fluorouracil (5-FU) in cancer patients has been associated with nephrotoxicity, which is greatly curbing its therapeutic application. The pathogenesis of 5-FU-induced nephrotoxicity is complex; however, oxidative stress-mediated inflammation is considered a central pathogenic factor. Urolithin B (UB), a product of ellagitannins, has recently been assigned diverse pharmacological activities due to its potent antioxidant and anti-inflammatory properties. Therefore, the current study explored the potential renoprotective effect of UB on 5-FU-induced nephrotoxicity in mice and illuminated its potential mechanistic pathways. In this study, administration of UB (50 and 100 mg/kg) mitigated 5-FU-induced elevated levels of kidney injury indices, including renal somatic index, serum creatinine, blood urea nitrogen, and serum cystatin C, that were concurrent with histopathological improvement. UB maintained renal oxidant/antioxidant balance and enhanced the nuclear factor-erythroid-2-related factor-2 (Nrf2)/heme oxygenase 1 (HO-1) as well as the silent information regulator factor 2-related enzyme 1 (SIRT1)/forkhead box O 3 (FOXO3) antioxidant protective responses. On the other hand, 5-FU-driven activation of the NF-кB/TNF-α inflammatory signaling was opposed by UB administration. Conclusively, UB protected against 5-FU-induced nephrotoxicity through dose-dependent antioxidant and anti-inflammatory effects. These effects are mediated mainly through upregulating Nrf2/HO-1 and SIRT-1/FOXO3 antioxidant responses with subsequent suppression of NF-κB inflammatory signaling., Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Intrahepatic cholestasis is a common clinical form of hepatobiliary injury characterized by the intrahepatic accumulation of toxic bile acids. Besides its antidiabetic activity, the dipeptidyl peptidase IV inhibitor sitagliptin (SG) has been recently assigned diverse pharmacological activities and therapeutic potential against different disorders owing to its emerging antioxidant and anti-inflammatory properties. The current study explored the potential hepatoprotective effect of SG on α-naphthyl isothiocyanate (ANIT)-induced cholestatic liver injury (CLI) in mice and investigate its possible targeted signaling pathways. Mice received SG (10 and 20 mg/kg) for four consecutive days, two days before and after a single oral administration of ANIT (75 mg/kg). Our results revealed that SG administration remarkably prevented ANIT-induced histopathological lesions in the liver and maintained hepatic functions and oxidative/antioxidant balance. Ultimately, SG counteracted the inflammatory response in the liver, as indicated by the marked suppression of hepatic expression of NF-κB, TNF-α, and IL-6. Moreover, it inhibited the endoplasmic reticulum (ER) stress response in the liver. These beneficial effects of SG were accompanied by upregulation of SIRT1, p-AMPK, and Nrf2 expressions while downregulating keap1 expression in the liver. In conclusion, this study is the first to demonstrate the ability of SG to protect against ANIT-induced CLI through modulating multiple signaling cascades, including SIRT1/AMPK, Nrf2/keap1, and NF-кB, which resulted in enhanced antioxidant capacity and repressed inflammatory and ER stress responses in the liver., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Alzheimer's disease (AD) presents a significant global health concern, characterized by neurodegeneration and cognitive decline. Neuroinflammation is a crucial factor in AD development and progression, yet effective pharmacotherapy remains elusive. Sulforaphane (SFN), derived from cruciferous vegetables and mainly from broccoli, has shown a promising effect via in vitro and in vivo studies as a potential treatment for AD. This study aims to investigate the possible prophylactic mechanisms of SFN against prefrontal cortex (PFC)-related recognition memory impairment induced by lipopolysaccharide (LPS) administration., Methodology: Thirty-six Swiss (SWR/J) mice weighing 18-25 g were divided into three groups ( n = 12 per group): a control group (vehicle), an LPS group (0.75 mg/kg of LPS), and an LPS + SFN group (25 mg/kg of SFN). The total duration of the study was 3 weeks, during which mice underwent treatments for the initial 2 weeks, with daily monitoring of body weight and temperature. Behavioral assessments via novel object recognition (NOR) and temporal order recognition (TOR) tasks were conducted in the final week of the study. Inflammatory markers (IL-6 and TNF), antioxidant enzymes (SOD, GSH, and CAT), and pro-oxidant (MDA) level, in addition to acetylcholine esterase (AChE) activity and active (caspase-3) and phosphorylated (AMPK) levels, were evaluated. Further, PFC neuronal degeneration, Aβ content, and microglial activation were also examined using H&E, Congo red staining, and Iba1 immunohistochemistry, respectively., Results: SFN pretreatment significantly improved recognition memory performance during the NOR and TOR tests. Moreover, SFN was protected from neuroinflammation and oxidative stress as well as neurodegeneration, Aβ accumulation, and microglial hyperactivity., Conclusion: The obtained results suggested that SFN has a potential protective property to mitigate the behavioral and biochemical impairments induced by chronic LPS administration and suggested to be via an AMPK/caspase-3-dependent manner.

Objectives: Given the adverse effect of liver injury on a multitude of body functions, it is vital to understand its underlying mechanism and how to overcome it. In this study, lipopolysaccharide (LPS) was used to induce liver injury, while sulforaphane (SFN), a natural phytochemical, was used as the antagonist to overcome the deleterious effect., Methods: Twenty-four mice were divided into three groups: Control group (0.9% saline), LPS induction group (0.75 mg/kg), and SFN treatment (25 mg/kg) followed by LPS induction group (0.75 mg/kg), all with access to food and water ad libitum . Blood samples from retro-orbital sinus were used to measure liver function through two aminotransferases (i.e., alanine transaminase [ALT] and aspartate transaminase [AST]) whereas liver homogenate was used to measure glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) (antioxidant activity markers); caspase-3 (apoptosis marker); malondialdehyde (MDA) (lipid peroxidation marker); and NO. AMP-activated protein kinase (AMPK), a cellular energy homeostasis and lipid metabolism sensor, was also measured. Statistical analysis including normalization, analysis of variance, Kruskal-Wallis test, and significance of P < 0.05 were applied to all collected data., Results: SFN treatment significantly attenuated all tests compared to the induced liver injury by LPS where significant reduction was observed in the levels of hepatic function markers (AST and ALT), lipid peroxidation marker (MDA) as well as apoptosis marker (caspase-3) whereas a marked increase was observed for antioxidant activity markers (SOD, CAT, and GSH) and AMPK., Conclusion: These results indicate the protective effect of SFN as it re-instated the levels of antioxidation while decreasing the level of the biomarkers, which were significantly increased during liver injury induction by LPS., Competing Interests: All the authors declared that there was no conflict and/or competing interests., (Copyright: © International Journal of Health Sciences.)

An early diagnosis of lung and colon cancer (LCC) is critical for improved patient outcomes and effective treatment. Histopathological image (HSI) analysis has emerged as a robust tool for cancer diagnosis. HSI analysis for a LCC diagnosis includes the analysis and examination of tissue samples attained from the LCC to recognize lesions or cancerous cells. It has a significant role in the staging and diagnosis of this tumor, which aids in the prognosis and treatment planning, but a manual analysis of the image is subject to human error and is also time-consuming. Therefore, a computer-aided approach is needed for the detection of LCC using HSI. Transfer learning (TL) leverages pretrained deep learning (DL) algorithms that have been trained on a larger dataset for extracting related features from the HIS, which are then used for training a classifier for a tumor diagnosis. This manuscript offers the design of the Al-Biruni Earth Radius Optimization with Transfer Learning-based Histopathological Image Analysis for Lung and Colon Cancer Detection (BERTL-HIALCCD) technique. The purpose of the study is to detect LCC effectually in histopathological images. To execute this, the BERTL-HIALCCD method follows the concepts of computer vision (CV) and transfer learning for accurate LCC detection. When using the BERTL-HIALCCD technique, an improved ShuffleNet model is applied for the feature extraction process, and its hyperparameters are chosen by the BER system. For the effectual recognition of LCC, a deep convolutional recurrent neural network (DCRNN) model is applied. Finally, the coati optimization algorithm (COA) is exploited for the parameter choice of the DCRNN approach. For examining the efficacy of the BERTL-HIALCCD technique, a comprehensive group of experiments was conducted on a large dataset of histopathological images. The experimental outcomes demonstrate that the combination of AER and COA algorithms attain an improved performance in cancer detection over the compared models.

Background: Chemically induced cirrhotic animal models are commonly used. However, they have limitations such as high mortalities and low yield of cirrhotic animals that limit their uses. Aims: To overcome limitations of the chemically induced cirrhotic animal model via combined administration of methotrexate (MTX) with CCl 4 and decrease their commonly used doses depending on the proposed synergetic cirrhotic effect. Methods: Rats were divided into six groups: normal (4 weeks), normal (8 weeks), MTX, CCl 4 (4 weeks), CCl 4 (8 weeks), and MTX + CCl 4 (4 weeks) groups. Animals' hepatic morphology and histopathological characterization were explored. Hepatic Bcl2 and NF-κB-p65 tissue contents were determined using the immunostaining technique, and hepatic tissue damage, oxidative status, and inflammatory status biochemical parameters were determined. Results: CCl 4 + MTX combined administration produced prominent cirrhotic liver changes, further confirmed by a substantial increase in oxidative stress and inflammatory parameters, whereas mortalities were significantly lower than in other treated groups. Conclusion: The present study introduced a new model that can significantly improve the major limitations of chemically induced cirrhotic animal models with new pathological features that mimic human cirrhosis. Compared to other chemically induced methods, the present model can save time, cost, and animal suffering., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mansouri, Ahmed, Alshaibi, Al-Bazi, Banjabi, Alsufiani, Aloqbi and Aboubakr.)

Results: The aqueous extracts of MAE were phytochemically analyzed, and the results revealed the presence of high concentrations of tannins, sterols, and isoprenoids (terpenoids), while steroids and flavonoids were found in moderate concentrations. The plant extract showed promising inhibition of the growth of gram-positive and gram-negative pathogens. It also showed that MAE has potential antihyperglycemic and antioxidant activities. Microscopic examination of the pancreas showed degenerative changes and atrophy associated with dilatation of the exocrine ducts in the STZ-induced diabetic rats, while the treatment revealed that the Langerhans islets were close to normal without any histopathological alteration., Conclusion: The present results suggested that an aqueous extract of MAE could be considered an efficient antidiabetic, antioxidant, and antimicrobial treatment in the future., Competing Interests: The authors declared that there is no conflict of interest., (Copyright © 2023 Rasha A. Mansouri et al.)

Household processing of fenugreek seeds and leaves, including soaking, germination, and boiling of the seeds, and air-drying of the leaves, has improved the levels of human consumption of the bitter seeds and increased the shelf life of fresh leaves, respectively. The potential anticancer activity of either unprocessed or processed fenugreek seeds or leaves and the relative expression of pro-apoptotic and anti-apoptotic genes of the studied cancerous cell lines exposed to IC 50 crude extracts was investigated to observe the apoptotic-inducing property of this plant as an anticancer agent. The protein expression of IKK-α and IKK-β, as inhibitors of NF-KB which exhibit a critical function in the regulation of genes involved in chronic inflammatory disorders, were studied in the tested cancerous cell lines. In this study, the anticancer activity of household-processed fenugreek leaves and seeds against HepG2, HCT-116, MCF-7, and VERO cell lines was measured using an MTT assay. DNA fragmentation of both HepG2 and MCF-7 was investigated by using gel electrophoresis. RT-PCR was used to evaluate the relative expression of each p53, caspase-3, Bax, and Bcl-2 genes, whereas ELISA assay determined the expression of caspase-3, TNF-α, and 8-OHDG genes. Western blotting analyzed the protein-expressing levels of IKK-α and IKK-β proteins in each studied cell line. Data showed that at 500 µg mL -1 , ADFL had the highest cytotoxicity against the HepG2 and HCT-116 cell lines. Although, each UFS and GFS sample had a more inhibitory effect on MCF-7 cells than ADFL. Gel electrophoresis demonstrated that the IC 50 of each ADFL, UFS, and GFS sample induced DNA fragmentation in HepG2 and MCF-7, contrary to untreated cell lines. Gene expression using RT-PCR showed that IC 50 doses of each sample induced apoptosis through the up-regulation of the p53, caspase-3, and Bax genes and the down-regulation of the Bcl-2 gene in each studied cell line. The relative expression of TNF-α, 8-OHDG, and caspase-3 genes of each HepG2 and MCF-7 cell line using ELISA assays demonstrated that ADFL, UFS, and GFS samples reduced the expression of TNF-α and 8-OHDG genes but increased the expression of the caspase-3 gene. Protein-expressing levels of IKK-α and IKK-β proteins in each studied cell line, determined using Western blotting, indicated that household treatments decreased IKK-α expression compared to the UFS sample. Moreover, the ADFL and SFS samples had the most activity in the IKK-β expression levels. Among all studied samples, air-dried fenugreek leaves and unprocessed and germinated fenugreek seeds had the most anti-proliferative and apoptotic-inducing properties against human HepG2, MCF-7, and HCT-116 cell lines, as compared to the VERO cell line. So, these crude extracts can be used in the future for developing new effective natural drugs for the treatment of hepatocellular, breast, and colon carcinomas.

Objective: Polycystic ovaries (PCO) is a hormonal disorder that is a leading cause of infertility. The formation of multiple persistent cysts and hormonal imbalance are hallmarks of PCO. Recent clinical studies reported a beneficial effect of the ketogenic diet (KD; high-fat, low-carbohydrate) on PCO. The aim of this study was to investigate the effect of the KD alone and in combination with metformin on letrozole-induced PCO in female rats., Methods: Female rats were grouped into control and PCO (letrozole; 1 mg/kg for 21 days). The PCO group was subdivided into PCO (non-treated), PCO-metformin (300 mg/kg), PCO rats fed with KD only, and PCO rats treated with metformin and fed with KD. All groups continued to receive letrozole during the 21-day treatment period. At the end of the experiment, serum and ovaries were collected for further analysis., Results: The untreated-PCO rats showed increased testosterone, LH/FSH ratio, and ovary weights. Disturbed apoptosis and proliferation balance were evident as a low caspase-3 activation and proliferating cell nuclear antigen expression and increased TGF-β expression. The KD improved the letrozole-induced effects, which was comparable to the effect of metformin. Combining the KD with metformin treatment additively enhanced the metformin effect., Conclusion: Our results indicate that the KD has a protective role against PCO in rats, especially when combined with metformin. This study reveals a potential therapeutic role of the KD in PCO, which could prompt valuable future clinical applications., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Al-Otaibi, Alghamdi, Al-Ghamdi, Mansouri, Ashraf and Omar.)

Icariin (ICA), a main active compound of the Epimedium genus, is used as an aphrodisiac in traditional Chinese herbal medicine. Despite its therapeutic efficacy, ICA displays reduced oral absorption, and therefore, low bioavailability hindered its clinical application. Implementing nanotechnology in the field of formulation has been a focus to improve the efficacy of ICA. In this regard, polymeric nanoparticles find a potential application as drug delivery systems. A nanosphere formula was designed, aiming to improve the drug's efficacy. The proposed ICA nanosphere formula (tocozeinolate) was optimized using D-optimal response surface design. The concentrations of ICA (X 1 ), D-α-tocopherol polyethylene glycol 1000 succinate (TPGS, X 2 ), zein (X 3 ), and sodium deoxycholate (SDC, X 4 ) expressed as percentages were investigated as quantitative independent variables. As per the experimental design, 23 formulations were developed, which were investigated for particle size (PS, nm), zeta potential (ZP, mV), and entrapment efficiency (EE, %) as response parameters. Numerical optimization and desirability approach were employed to predict the optimized variable levels that, upon combination, could result in minimized size and maximized zeta potential and ICA entrapment. The optimized ICA-tocozeinolate nanospheres showed a particle size of 224.45 nm, zeta potential of 0.961 mV, and drug entrapment of 65.29% that coincide well with the predicted values. The optimized ICA-tocozeinolate nanospheres were evaluated for sexual behavior in Wistar male rats compared to raw ICA at equivalent doses (20 mg/kg). In vivo assessment results showed significant sexual behavior enhancement by the optimized formulation, as evidenced by decreased average time of both mount latency (ML) and ejaculation latency (EL) to almost half those of raw ICA. Additionally, intromission latency (IL) time was reduced by 41% compared to the raw ICA. These results highlighted the potential of the proposed ICA-tocozeinolate nanospheres as a promising platform for improving the delivery and efficacy of therapeutic agents.

Background: Lipopolysaccharide (LPS) administration is one of the most commonly used methods for inducing inflammation in animal models. Several animal studies have investigated the effects of acute and chronic peripheral administration of LPS on cognitive impairment. However, no previous study has compared the effects of different doses of chronically administered LPS on recognition memory performance., Aim: Here, we aimed to investigate the optimal dose of chronically administered LPS for the induction of recognition memory impairment in mice., Materials and Methods: LPS at different doses (0.25, 0.50 and 0.75 mg/kg) was administered to SWR/J mice daily for 7 days. On day 9, the open field, novel object recognition and novel arm discrimination behavioral tests were performed. Additionally, prefrontal cortical histological examination was conducted., Results: Compared with the control group, mice injected with 0.75 mg/kg LPS notably showed no object preference (familiar vs. novel), a reduction in the discrimination index, and spatial recognition impairment. Administration of the 0.25 and 0.50 mg/kg doses of LPS showed a preference for the novel object compared with the familiar object, had no significant impact on the discrimination index, and caused spatial recognition impairment. These behavioral results are in line with the histological examination of the prefrontal cortex, which revealed that the 0.75 mg/kg dose produced the most histological damage., Conclusions: Our findings suggest that for chronic peripheral administration of LPS, 0.75 mg/kg is the optimal dose for inducing neuroinflammation-associated recognition memory deficits., Competing Interests: The author declares no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system characterized by the demyelination of nerves, neural degeneration, and axonal loss. Cognitive impairment, including memory decline, is a significant feature in MS affecting up to 70% of patients. Thereby, it substantially impacts patients' quality of life. Biochanin A (BCA) is an o-methylated isoflavone with a wide variety of pharmacological activities, including antioxidant, anti-inflammatory, and neuroprotective activities. Thus, this study aimed to investigate the possible protective effects of BCA on memory decline in the cuprizone (CPZ) model of MS. Thirty Swiss albino male mice (SWR/J) were randomly divided into three groups (n = 10): control (normal chow + i.p. 1:9 mixture of DMSO and PBS), CPZ (0.2% w / w of CPZ mixed into chow + i.p. 1:9 mixture of DMSO and PBS), and CPZ + BCA (0.2% w / w of CPZ mixed into chow + i.p. 40 mg/kg of BCA). At the last week of the study (week 5), a series of behavioral tasks were performed. A grip strength test was performed to assess muscle weakness while Y-maze, novel object recognition task (NORT), and novel arm discrimination task (NADT) were performed to assess memory. Additionally, histological examination of the hippocampus and the prefrontal cortex (PFC) were conducted. BCA administration caused a significant increase in the grip strength compared with the CPZ group. Additionally, BCA significantly improved the mice's spatial memory in the Y-maze and recognition memory in the NORT and the NADT compared with the CPZ group. Moreover, BCA mitigated neuronal damage in the PFC and the hippocampus after five weeks of administration. In conclusion, our data demonstrates the possible protective effect of BCA against memory deterioration in mice fed with CPZ for five weeks.

Lung cancer is a dangerous type of cancer in men and the third leading cause of cancer-related death in women, behind breast and colorectal cancers. Thymoquinone (THQ), a main compound in black seed essential oils, has a variety of beneficial effects, including antiproliferative, anti-inflammatory, and antioxidant properties. On the other hand, scorpion venom peptides (SV) induce apoptosis in the cancer cells, making it a promising anticancer agent. THQ, SV, and Phospholipon ® 90H (PL) were incorporated in a nano-based delivery platform to assess THQ's cellular uptake and antiproliferative efficacy against a lung cancer cell line derived from human alveolar epithelial cells (A549). Several nanovesicles were prepared and optimized using factorial experimental design. The optimized phytosome formulation contained 79.0 mg of PL and 170.0 mg of SV, with vesicle size and zeta potential of 209.9 nm and 21.1 mV, respectively. The IC50 values revealed that A549 cells were significantly more sensitive to the THQ formula than the plain formula and THQ. Cell cycle analysis revealed that THQ formula treatment resulted in significant cell cycle arrest at the S phase, increasing cell population in this phase by 22.1%. Furthermore, the THQ formula greatly increased cell apoptosis (25.17%) when compared to the untreated control (1.76%), plain formula (11.96%), or THQ alone (13.18%). The results also indicated that treatment with THQ formula significantly increased caspase-3, Bax, Bcl-2, and p53 mRNA expression compared to plain formula and THQ. In terms of the inflammatory markers, THQ formula significantly reduced the activity of TNF-α and NF-κB in comparison with the plain formula and THQ only. Overall, the findings from the study proved that a phytosome formulation of THQ could be a promising therapeutic approach for the treatment of lung adenocarcinoma.

Hyperthermia therapy is now being used to treat cancer. However, understanding the pattern of temperature increase in biological tissues during hyperthermia treatment is essential. In recent years, many physicians and engineers have studied the use of computational and mathematical models of heat transfer in biological systems. The rapid progress in computing technology has intrigued many researchers. Many medical procedures also use engineering techniques and mathematical modeling to ensure their safety and assess the risks involved. One such model is the modified Pennes bioheat conduction equation. This paper provides an analytical solution to the modified Pennes bioheat conduction equation with a single relaxation time by incorporating in it the (MGT) equation. The suggested model examines heat transport in biological tissues as forming an infinite concentric spherical region during magnetic fluid hyperthermia. To investigate thermal reactions caused by temperature shock, specifically the influence of heat generation through heat treatment on a skin tumor [AEGP9], the Laplace transformation, and numerical inverse transformation methods are used. This model was able to explain the effects of different therapeutic approaches such as cryotherapy sessions, laser therapy, and physical occurrences, transfer, metabolism support, and blood perfusion. Comparison of the numerical results of the suggested model with those in the literature confirmed the validity of the model's numerical results.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is marked by cognitive dysfunctions and the existence of neuropathological hallmarks such as amyloid plaques, and neurofibrillary tangles. It has been observed that a persistent immune response in the brain has appeared as another neuropathological hallmark in AD. The sustained activation of the microglia, the brain's resident macrophages, and other immune cells has been shown to aggravate both tau and amyloid pathology and may consider as a connection in the AD pathogenesis. However, the basic mechanisms that link immune responses in the pathogenesis of AD are unclear until now since the process of neuroinflammation can have either a harmful or favorable effect on AD, according to the phase of the disease. Numerous researches recommend that nutritional fruits, as well as vegetables, possess neurodefensive properties against the detrimental effects of neuroinflammation and aging. Moreover, these effects are controlled by diverse phytochemical compounds that are found in plants and demonstrate anti-inflammatory, neuroprotective, as well as other beneficial actions. In this review, we focus on the link of neuroinflammation in AD as well as highlight the probable mechanisms of alkaloidal phytochemicals to combat the neuroinflammatory aspect of AD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The recent outbreak of the COVID-2019 (coronavirus disease 2019) due to the infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has realized the requirement of alternative therapeutics to mitigate and alleviate this lethal infection. These alternative therapies are effective when they are started at the initial stage of the infection. Some drugs that were used in previous other related infections SARS-CoV-2003 and Middle East respiratory syndrome coronavirus (MERS-CoV)-2012 could be potentially active against currently emerging SARS-CoV-2. This fact imparts some rationale of current interventions, in the absence of any specific therapeutics for SARS-CoV-2. It is imperative to focus on the available antimicrobial and adjunct therapies during the current emergency state and overcome the challenges associated with the absence of robust controlled studies. There is no established set of drugs to manage SARS-CoV-2 infected patients. However, closely following patients' conditions and responding with the dosage guidelines of available drugs may significantly impact our ability to slow down the infection. Of note, it depends upon the condition of the patients and associated comorbid; therefore, the health workers need to choose the drug combinations judiciously until COVID-19 specific drug or vaccine is developed with the collective scientific rigor. In this article, we reviewed the available antimicrobial drug, supportive therapies, and probable high importance vaccines for the COVID-19 treatment., (Copyright © 2020 Kumar, Srivastava, Singh, Siddiqui, Mansouri, Abdulhakim, Bin-Jumah, Alkahtani, Abdel-Daim and Uddin.)

Neurodegeneration is the progressive loss of neuronal structures and functions that lead to copious disorders like Alzheimer's (AD), Parkinson's (PD), Huntington's (HD), amyotrophic lateral sclerosis (ALS), and other less recurring diseases. Aging is the prime culprit for most neurodegenerative events. Moreover, the shared pathogenic factors of many neurodegenerative processes are inflammatory responses and oxidative stress (OS). Unfortunately, it is very complicated to treat neurodegeneration and there is no effective remedy. The rapid progression of the neurodegenerative diseases that exacerbate the burden and the concurrent absence of effective treatment strategies force the researchers to investigate more therapeutic approaches that ultimately target the causative factors of the neurodegeneration. Phytochemicals have great potential to exert their neuroprotective effects by targeting various mechanisms, such as OS, neuroinflammation, abnormal protein aggregation, neurotrophic factor deficiency, disruption in mitochondrial function, and apoptosis. Therefore, this review represents the molecular mechanisms of neuroprotection by multifunctional phytochemicals to combat age-linked neurodegenerative disorders., Competing Interests: Declaration of competing interest The authors proclaim no competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is the leading cause of dementia worldwide. Even though the number of AD patients is rapidly growing, there is no effective treatment for this neurodegenerative disorder. At present, implementation of effective treatment approaches for AD is vital to meet clinical needs. In AD research, priorities concern the development of disease-modifying therapeutic agents to be used in the early phases of AD and the optimization of the symptomatic treatments predominantly dedicated to the more advanced AD stages. Until now, available therapeutic agents for AD treatment only provide symptomatic treatment. Since AD pathogenesis is multifactorial, use of a multimodal therapeutic intervention addressing several molecular targets of AD-related pathological processes seems to be the most practical approach to modify the course of AD progression. It has been demonstrated through numerous studies, that the clinical efficacy of combination therapy (CT) is higher than that of monotherapy. In case of AD, CT is more effective, mostly when started early, at slowing the rate of cognitive impairment. In this review, we have covered the major studies regarding CT to combat AD pathogenesis. Moreover, we have also highlighted the safety, tolerability, and efficacy of CT in the treatment of AD.

Background: Cranberry has been studied as a potential anticancer agent as it is capable of inducing apoptosis within cancer cells. The aim of this study was to better define the mechanism by which cranberry triggers apoptosis in HL-60 cells., Methods: The study was carried on cranberry extracts (CB). Anti-apoptotic B-cell lymphoma-2 (BCL-2) and pro-apoptotic BCL-2-associated death promoter death (BAD) proteins in cell lysates were detected through Western blotting techniques. Equivalent protein loading was confirmed through anti-α-tubulin antibody., Results: The results showed that treatment of HL-60 cells with CB causes a significant increase in the levels of caspase-9 and caspases-3/7 and increased mitochondrial outer membrane permeability, leading to the release of cytochrome C and Smac. These apoptotic events were associated with a significant decrease in protein kinase B (AKT) phosphorylation, which caused significant increase in BAD de-phosphorylation and promoted a sequence of events that led to intrinsic apoptosis., Conclusion: The study findings have described a molecular framework for CB-initiated apoptosis in HL-60 cells and suggested a direction for future in vivo studies investigating the anticancer effect of cranberry.

Objective: This study aimed to assess the relationship between chemerin and visfatin concentrations and insulin resistance in Saudi women with hyperthyroidism., Materials and Methods: Seventy healthy participants and 70 participants with hyperthyroidism were recruited for the study. Concentrations of chemerin, visfatin, thyroid profile, fasting glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) were measured., Results: Hyperthyroid patients showed significantly higher concentrations of fasting glucose and insulin ( P < 0.001) and significant increases in HOMA-IR values than the control group. Spearman's correlation coefficient analysis showed that thyroid-stimulating hormone was negatively correlated with glucose, insulin, and HOMA-IR, while free triiodothyronine was positively correlated with the same parameters. Total triiodothyronine and total thyroxine also showed a significant positive correlation with glucose, and the levels of thyroglobulin were also positively correlated with insulin and HOMA-IR. Furthermore, chemerin levels correlated positively with glucose, insulin, and HOMA-IR. Inversely, visfatin was negatively correlated with insulin and HOMA-IR., Conclusion: A significant relationship was observed between adipokines and thyroid profile, glucose, insulin, and insulin resistance in hyperthyroid patients. This suggests that visfatin and chemerin levels might affect insulin sensitivity in conjunction with thyroid hormones and thus may alter the metabolism of glucose and leads to insulin resistance.

Objectives: The aim of this study was to investigate the potential influence of hyperthyroidism on serum chemerin, visfatin, and omentin concentrations. The relationship between these adipokines and thyroid profile values was also investigated., Methods: A total of 140 female Saudi participants aged 20-45 years were recruited and divided into two groups, the euthyroid control group ( n = 70) and the hyperthyroidism group ( n = 70). Chemerin, visfatin, omentin, and thyroid profile including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), total thyroxine (TT4), and thyroglobulin were measured for all participants., Results: Serum chemerin levels were significantly higher in patients with hyperthyroidism compared to the controls. In contrast, serum visfatin and omentin concentrations were significantly lower in hyperthyroid patients than controls. Moreover, serum chemerin concentrations were positively correlated with TT3, TT4, and FT3 and negatively correlated with TSH and FT4. A negative correlation was also found between FT4 and TT4 and serum visfatin concentrations. Inversely, TSH correlated positively with serum visfatin levels. No significant correlation was observed between serum omentin concentrations and any of the thyroid profile variables except FT3., Conclusion: Hyperthyroidism influences serum chemerin, visfatin, and omentin concentrations, and these adipokines are correlated with thyroid hormones.