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Omsk Hemorrhagic Fever Virus (OHFV) is an RNA virus with a single-stranded, positive-sense genome. It is classified under the Flaviviridae family. The genome of this virus is 98% similar to the Alkhurma hemorrhagic fever virus (AHFV), which belongs to the same family. Cases of the virus have been reported in various regions of Saudi Arabia. Both OHFV and AHFV have similarities in pathogenic polyprotein targets. No effective and licensed vaccines are available to manage OHFV infections. Therefore, an effective and safe vaccine is required that can activate protective immunity against OHFV. The current study aimed to design a multiepitope subunit vaccine against the OHFV utilizing several immunoinformatic tools. The polyprotein of OHFV was selected and potent antigenic, non-allergenic, and nontoxic cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and linear B-lymphocyte (LBL) epitopes were chosen. After screening, eight (8) CTL, five (5) HTL, and six (6) B cell epitopes were joined with each other using different linkers. Adjuvant human beta defensin-2 was also linked to the epitopes to increase vaccine antigenic and immunogenic efficiency. The designed vaccine was docked with Toll-like receptor 4 (TLR4) as it activates and induces primary and secondary immune responses against OHFV. Codon optimization was carried out, which resulted in a CAI value of 0.99 and 53.4% GC contents. In addition, the construct was blindly docked to the TLR4 immune receptor and subjected to conformational dynamics simulation analysis to interpret the intricate affinity and comprehend the time-dependent behavior. Moreover, it was predicted that immune responses to the developed vaccine construct reported formation of strong humoral and cellular immune cells. Therefore, the proposed vaccine may be considered in experimental assays to combat OHFV infections. Laboratory experiments for the above predictions are essential in order to evaluate the effectiveness, safety, and protective properties of the subject in question.

Over the past three decades, the popularity of cosmetic and personal care products has skyrocketed, largely driven by social media influence and the propagation of unrealistic beauty standards, especially among younger demographics. These products, promising enhanced appearance and self-esteem, have become integral to contemporary society. However, users of synthetic, chemical-based cosmetics are exposed to significantly higher risks than those opting for natural alternatives. The use of synthetic products has been associated with a variety of chronic diseases, including cancer, respiratory conditions, neurological disorders, and endocrine disruption. This review explores the toxicological impact of beauty and personal care products on human health, highlighting the dangers posed by various chemicals, the rise of natural ingredients, the intricate effects of chemical mixtures, the advent of nanotechnology in cosmetics, and the urgent need for robust regulatory measures to ensure safety. The paper emphasizes the necessity for thorough safety assessments, ethical ingredient sourcing, consumer education, and collaboration between governments, regulatory bodies, manufacturers, and consumers. As we delve into the latest discoveries and emerging trends in beauty product regulation and safety, it is clear that the protection of public health and well-being is a critical concern in this ever-evolving field., Competing Interests: The author declares 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 © 2024 Alnuqaydan.)

This comprehensive review delves into the pivotal role of the tumor microenvironment (TME) in cancer metastasis and therapeutic response, offering fresh insights into the intricate interplay between cancer cells and their surrounding milieu. The TME, a dynamic ecosystem comprising diverse cellular and acellular elements, not only fosters tumor progression but also profoundly affects the efficacy of conventional and emerging cancer therapies. Through nuanced exploration, this review illuminates the multifaceted nature of the TME, elucidating its capacity to engender drug resistance via mechanisms such as hypoxia, immune evasion, and the establishment of physical barriers to drug delivery. Moreover, it investigates innovative therapeutic approaches aimed at targeting the TME, including stromal reprogramming, immune microenvironment modulation, extracellular matrix (ECM)-targeting agents, and personalized medicine strategies, highlighting their potential to augment treatment outcomes. Furthermore, this review critically evaluates the challenges posed by the complexity and heterogeneity of the TME, which contribute to variable therapeutic responses and potentially unintended consequences. This underscores the need to identify robust biomarkers and advance predictive models to anticipate treatment outcomes, as well as advocate for combination therapies that address multiple facets of the TME. Finally, the review emphasizes the necessity of an interdisciplinary approach and the integration of cutting-edge technologies to unravel the intricacies of the TME, thereby facilitating the development of more effective, adaptable, and personalized cancer treatments. By providing critical insights into the current state of TME research and its implications for the future of oncology, this review highlights the dynamic and evolving landscape of this field., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Herbal medicine is a medical system based on the utilization of plants or plant extracts for therapy. The continual increase in global consumption and the trade of herbal medicine has raised safety concerns in many regions. These concerns are mainly linked to microbial contamination, which could spread infections with multi-resistant bacteria in the community, and heavy metal contamination that may lead to cancers or internal organs' toxicity., Methods: This study was performed using an experimental design. A total of 47 samples, herbal medicine products sold in local stores in Qassim region, were used in the experiments. They were tested for bacterial contamination, alongside 32 samples for heavy metal analysis. Bacterial contamination was determined by the streak plate method and further processed to determine their antimicrobial susceptibility patterns using MicroScan WalkAway96 pulse; heavy metals were determined using a spectrometer instrument., Results: A total of 58 microorganisms were isolated. All samples were found to be contaminated with at least one organism except three samples. The majority of the isolated bacterial species were gram negative bacteria, such as Klebsiella spp., Pseudomonas spp. and E. coli., which could be of fecal origin and may lead to pneumonia, skin, or internal infections. Furthermore, most of the gram-positive bacteria were found to be multi-drug resistant. Moreover, for heavy metals, all samples had levels exceeding the regulatory limits., Conclusion: This study demonstrated the presence of bacteria and heavy metals in samples of herbal medicines. Using these contaminated products may spread resistant infections, metal toxicities, or even cancers in the community., (© 2023. The Author(s).)

The current study evaluates the cytotoxicity, mode of cell death and chemical analysis of selected beauty products and evaluation of the protective effect of Tamarix articulata (TA) extract against toxicity induced by beauty products in skin fibroblasts (Hs27). MTT and Crystal violet (CV) assays were used to determine the dose-dependent cytotoxic effects of beauty products against Hs27 fibroblasts. DNA fragmentation assay and annexin-V staining were conducted to determine the mode of cell killing induced by evaluated beauty products. Quantification of reactive oxygen species (ROS) and antioxidant enzyme levels were used to evaluate the oxidative stress. Chemical analysis and heavy metals were evaluated to determine beauty products. Pre-treatment with TA extract for different time points followed by time-dependent exposure with beauty products to assess the protective effect of TA extract in Hs27 cells was analyzed by MTT and CV assays. Owing to the presence of various harmful heavy metals such as arsenic (As), chromium (Cr), cadmium (Cd), nickel (Ni), and lead (Pb) in beauty products, our results revealed that all beauty products induce significant cytotoxicity over time (1, 4 h) in a dose-dependent (125, 250, 500 μg/mL) manner. DNA fragmentation assay, quantification of apoptosis by annexin-V staining, determination of ROS and antioxidant enzymes (CAT, GSH-Px and SOD) revealed that the induced cytotoxicity was caused by oxidative stress-mediated apoptosis. However, pre-incubation with a safe dose (50 μg/mL) of TA for different times (24, 48 h) followed by exposure to various doses (62.5, 125, 250, 500 μg/mL) of beauty products for different times (1, 4 h) revealed significant (*p≤0.05, **p≤0.01) protection against beauty product-mediated cytotoxicity. The effect was more pronounced for 1 h exposure to beauty products compared to 4 h. Our study demonstrates that the due to the presence of heavy metals in synthetic beauty products exhibit marked toxicity to skin fibroblasts due to oxidative stress-mediated apoptosis. However, the presence of abundant bioactive polyphenols with promising antiscavenging activity in TA extracts significantly nullifies cytotoxicity promoted by examined beauty products in skin fibroblasts (Hs27)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Alnuqaydan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Physiological barrier function is very difficult to replicate in vitro. This situation leads to poor prediction of candidate drugs in the drug development process due to the lack of preclinical modelling for intestinal function. By using 3D bioprinting, we generated a colitis-like condition model that can evaluate the barrier function of albumin nanoencapsulated anti-inflammatory drugs. Histological characterization demonstrated the manifestation of the disease in 3D-bioprinted Caco-2 and HT-29 constructs. A comparison of proliferation rates in 2D monolayer and 3D-bioprinted models was also carried out. This model is compatible with currently available preclinical assays and can be implemented as an effective tool for efficacy and toxicity prediction in drug development.

Neuropsychiatric disorders that affect the central nervous system cause considerable pressures on the health care system and have a substantial economic burden on modern societies. The present treatments based on available drugs are mostly ineffective and often costly. The molecular process of neuropsychiatric disorders is closely connected to modifying the genetic structures inherited or caused by damage, toxic chemicals, and some current diseases. Gene therapy is presently an experimental concept for neurological disorders. Clinical applications endeavor to alleviate the symptoms, reduce disease progression, and repair defective genes. Implementing gene therapy in inherited and acquired neurological illnesses entails the integration of several scientific disciplines, including virology, neurology, neurosurgery, molecular genetics, and immunology. Genetic manipulation has the power to minimize or cure illness by inducing genetic alterations at endogenous loci. Gene therapy that involves treating the disease by deleting, silencing, or editing defective genes and delivering genetic material to produce therapeutic molecules has excellent potential as a novel approach for treating neuropsychiatric disorders. With the recent advances in gene selection and vector design quality in targeted treatments, gene therapy could be an effective approach. This review article will investigate and report the newest and the most critical molecules and factors in neuropsychiatric disorder gene therapy. Different genome editing techniques available will be evaluated, and the review will highlight preclinical research of genome editing for neuropsychiatric disorders while also evaluating current limitations and potential strategies to overcome genome editing advancements., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Targeting pentose phosphate pathway (PPP) enzymes has emerged as a promising strategy to combat cancer. 6-Phosphogluconate dehydrogenase (6-PGD), the third critical enzyme of the PPP, catalyzes oxidative decarboxylation of 6-phosphogluconate (6-PG) to produce ribulose-5-phosphate (Ru-5-P) and CO2. Overexpression of 6-PGD has been reported in multiple cancers and is recognized as a potential anticancer drug target. The current study is focused on the utilization of indispensable virtual screening tools for structure-based drug discovery. During the study, 17,000 natural compounds were screened against the 3-phosphoglycerate (3-PG) binding site of 6-PGD through a molecular operating environment (MOE), which revealed 115 inhibitors with higher selectivity and binding affinity. Out of the 115 best-fit compounds within the 6-PGD binding cavity, 15 compounds were selected and optimized through stringent in silico ADMET assessment models that justified the desirable pharmacokinetic, pharmacodynamic and physicochemical profiles of 5 ligands. Further protein−ligand stability assessment through molecular dynamics (MD) simulation illustrated three potential hits, secoisolariciresinol, syringaresinol and cleomiscosin A, with stable confirmation. Moreover, 6-PGD inhibitor validation was performed by an in vitro enzymatic assay using human erythrocytes purified 6-PGD protein and A549 cell lysate protein. The results of the in vitro assays supported the in silico findings. In order to gain insight into the anticancer activity of the aforementioned compounds, they were subjected to CLC-Pred, an in silico cytotoxicity browsing tool, which proved their anticancer activity against several cancer cell lines at Pa > 0.5. Additionally, a confirmation for in silico cytotoxicity was made by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for commercially available hits syringaresinol and cleomiscosin A against lung cancer (A549) cells. The results demonstrated that syringaresinol has an IC50 value of 36.9 μg/mL, while cleomiscosin A has an IC50 value of 133 μg/mL. After MTT, flow cytometry analysis confirmed that compounds induced apoptosis in A549 cells in a dose-dependent manner. This study suggested that the respective lignan compounds can serve as lead candidates for lung cancer therapy via 6-PGD inhibition. Furthermore, in vivo experiments need to be conducted to confirm their efficacy.

Inflammation and oxidative stress are interrelated processes that represent the underlying causes of several chronic inflammatory diseases that include asthma, cystic fibrosis, chronic obstructive pulmonary disease (COPD), allergies, diabetes, and cardiovascular diseases. Macrophages are key initiators of inflammatory processes in the body. When triggered by a stimulus such as bacterial lipopolysaccharides (LPS), these cells secrete inflammatory cytokines namely TNF-α that orchestrate the cellular inflammatory process. Simultaneously, pro-inflammatory stimuli induce the upregulation of inducible nitric oxide synthase (iNOS) which catalyzes the generation of high levels of nitric oxide (NO). This, together with high concentrations of reactive oxygen species (ROS) produced by macrophages, mediate oxidative stress which, in turn, exacerbates inflammation in a feedback loop, resulting in the pathogenesis of several chronic inflammatory diseases. Berberine is a phytochemical embedded with potent in vitro anti-inflammatory and antioxidant properties, whose therapeutic application is hindered by poor solubility and bioavailability. For this reason, large doses of berberine need to be administered to achieve the desired pharmacological effect, which may result in toxicity. Encapsulation of such a drug in liquid crystalline nanoparticles (LCNs) represents a viable strategy to overcome these limitations. We encapsulated berberine in phytantriol-based LCNs (BP-LCNs) and tested the antioxidant and anti-inflammatory activities of BP-LCNs in vitro on LPS-induced mouse RAW264.7 macrophages. BP-LCNs showed potent anti-inflammatory and antioxidant activities, with significant reduction in the gene expressions of TNF-α and iNOS, followed by concomitant reduction of ROS and NO production at a concentration of 2.5 µM, which is lower than the concentration of free berberine concentration required to achieve similar effects as reported elsewhere. Furthermore, we provide evidence for the suitability for BP-LCNs both as an antioxidant and as an anti-inflammatory agent with potential application in the therapy of chronic inflammatory diseases.

This study evaluates the hepatoprotective activity of a Tamarix articulata extract against carbon tetrachloride-mediated hepatotoxicity in Wistar rats. Our results demonstrated that the oral administration of Tamarix articulata extract (50 mg/kg b.w.) significantly restored the serum levels of liver enzymes and antioxidant parameters (superoxide dismutase, catalase, glutathione reductase, and thiobarbituric reactive substances). Histopathology analysis revealed that Tamarix articulata extract significantly reduced hepatic fibrosis by inhibiting the necrosis of hepatocytes. Furthermore, serum pro-inflammatory (tumor necrosis factor-alpha, tumor growth factor-beta, and interleukin-6) markers were significantly restored. However, the anti-inflammatory cytokine adiponectin levels increased to normal levels in the group treated with Tamarix articulata extract. Additionally, we observed diminished reactive oxygen species production and the depolarization of mitochondrial membrane potential in hepatocytes extracted from animal livers treated with Tamarix articulata extract. Our findings suggest that Tamarix articulata extract prevents liver fibrosis induced by carbon tetrachloride and decreases the necrotic population of hepatocytes. These events restored the antioxidant enzymatic activity, serum levels of liver enzymes, and pro-inflammatory markers to their normal levels.

The incidence of hospital- and community-acquired infections has been dramatically increased worldwide. Accordingly, hands hygiene and the use of disinfectants have been increased leading to the expansion in hand sanitizers production to meet public demand. This study was conducted to assess the efficiency of common disinfectants in the market of Riyadh, Saudi Arabia in inhibiting the microbial growth during the time of Coronavirus disease 2019 (COVID-19) pandemic. Five bacterial strains of commonly hospital-acquired infections (Pseudomonas aeruginosa, Escherichia coli, Salmonella enteritidis, Staphylococcus aureus, and Enterococcus faecalis) (ATCC reference strains and clinical isolates) were examined for their susceptibility against 18 disinfectants collected from the Saudi market. The tested 18 disinfectants were broadly clustered into different groups based on their active chemical composition as following: 12 products contained alcohol, 2 products had chlorhexidine, 3 products contained mixed concentration of alcohol/chlorhexidine and 1 product had a mixture of chlorhexidine/Hexamidine/Chlorocresol. By measuring the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC), our results revealed that all the 18 disinfectants have reduced the microbial growth of all the tested strains. Generally, the MICs and the MBCs for the clinical strains are higher than those of the reference strains. Taken together, our findings showed that all tested products have high disinfectants' killing rate against microbes of different origins, which suggest the high quality of these disinfectants and the good surveillance practice by the local authorities in Saudi Arabia., Competing Interests: The authors report no conflict of interest in this work.

(1) Background: Inflammation is one of the primary responses of the immune system and plays a key role in the pathophysiology of various diseases. Recent reports suggest that various phytochemicals exhibit promising anti-inflammatory and immunomodulation activities with relatively few undesirable effects, thus offering a viable option to deal with inflammation and associated diseases. The current study evaluates the anti-inflammatory and immunomodulatory effects of withaferin A (WA) in immune cells extracted from BALB/c mice. (2) Methods: MTT assays were performed to assess the cell viability of splenocytes and anti-inflammatory doses of WA. Under aseptic conditions, the isolation of macrophages and splenocytes from BALB/c mice was performed to investigate the anti-inflammatory effects of WA. Analysis of the expression of proinflammatory cytokines and associated signaling mediators was performed using proinflammatory assay kits, real-time polymerase chain reaction (RT-PCR), and immunoblotting, while the quantification of B and T cells was performed by flow cytometry. (3) Results: Our results demonstrated that WA exhibits anti-inflammatory and immunomodulatory effects in LPS-stimulated macrophages and splenocytes derived from BALB/c mice, respectively. Mechanistically, we found that WA promotes an anti-inflammatory effect on LPS-stimulated macrophages by attenuating the secretion and expression of proinflammatory cytokines TNF-α, IL-1β, IL-6, and the inflammation modulator NO, both at the transcriptional and translational level, respectively. Further, WA inhibits LPS-stimulated inflammatory signaling by dephosphorylation of p-Akt-Ser473 and p-ERK1/2. This dephosphorylation does not allow IĸB-kinase activation to disrupt IĸB-NF-ĸB interaction. The consistent interaction of IĸB with NF-ĸB in WA-treated cells attenuates the activation of downstream inflammatory signaling mediators Cox-2 and iNOS expression, which play crucial roles in inflammatory signaling. Additionally, we observed significant immunomodulation of LPS-stimulated spleen-derived lymphocytes by suppression of B (CD19) and T (CD4 + /CD8 + ) cell populations after treatment with WA. (4) Conclusion: WA exhibits anti-inflammatory and immunomodulatory activity by modulating Akt/ERK/NF-kB-mediated inflammatory signaling in macrophages and immunosuppression of B (CD19) and T cell (CD4 + /CD8 + ) populations in splenocytes after LPS stimulation. These results suggest that WA could act as a potential anti-inflammatory/immunomodulatory molecule and support its use in the field of immunopharmacology to modulate immune system cells.

Enterobacter cloacae (EC) is a significant emerging pathogen that is occasionally associated with lung infection, surgical site infection, urinary infection, sepsis, and outbreaks in neonatal intensive care units. In light of the fact that there is currently no approved vaccine or therapeutic option for the treatment of EC, the current study was developed to concentrate on applications based on modern computational approaches to design a multi-epitope-based E. cloacae peptide vaccine (MEBEPV) expressing the antigenic determinants prioritized from the EC genome. Integrated computational analyses identified two potential protein targets (phosphoporin protein-PhoE and putative outer-membrane porin protein) for further exploration on the basis of pangenome subtractive proteomics and immunoinformatic in-depth examination of the core proteomes. Then, a multi-epitope peptide vaccine was designed, which comprised shortlisted epitopes that were capable of eliciting both innate and adaptive immunity, as well as the cholera toxin's B-subunit, which was used as an adjuvant in the vaccine formulation. To ensure maximum expression, the vaccine's 3D structure was developed and the loop was refined, improving the stability by disulfide engineering, and the physicochemical characteristics of the recombinant vaccine sequence were found to be ideal for both in vitro and in vivo experimentation. Blind docking was then used for the prediction of the MEBEPV predominant blinding mode with MHCI, MHCII, and TLR3 innate immune receptors, with lowest global energy of -18.64 kJ/mol, -48.25 kJ/mol, and -5.20 kJ/mol for MHC-I, MHC-II, and TLR-4, respectively, with docked complexes considered for simulation. In MD and MMGBSA investigations, the docked models of MEBEPV-TLR3, MEBEPV-MHCI, and MEBEPV-MHCII were found to be stable during the course of the simulation. MM-GBSA analysis calculated -122.17 total net binding free energies for the TLR3-vaccine complex, -125.4 for the MHC I-vaccine complex, and -187.94 for the MHC II-vaccine complex. Next, MM-PBSA analysis calculated -115.63 binding free energy for the TLR3-vaccine complex, -118.19 for the MHC I-vaccine complex, and -184.61 for the MHC II-vaccine complex. When the vaccine was tested in silico, researchers discovered that it was capable of inducing both types of immune responses (cell mediated and humoral) at the same time. Even though the suggested MEBEPV has the potential to be a powerful contender against E. cloacae -associated illnesses, further testing in the laboratory will be required before it can be declared safe and immunogenic.

Onosma bracteata Wall. is an important medicinal and immunity-enhancing herbs. This plant is commonly used in the preparation of traditional Ayurvedic drugs to treat numerous diseases. Inspired by the medicinal properties of this plant, the present study aimed to investigate the antiproliferative potential and the primary molecular mechanisms of the apoptotic induction against human osteosarcoma (MG-63) cells. Among all the fractions isolated from O. bracteata , ethyl acetate fraction (Obea) showed good antioxidant activity in superoxide radical scavenging assay and lipid peroxidation assay with an EC 50 value of 95.12 and 80.67 µg/mL, respectively. Silica gel column chromatography of ethyl acetate (Obea) fraction of O. bracteata yielded a pure compound, which was characterized by NMR, FTIR, and HR-MS analysis and was identified as 1,2-benzene dicarboxylic acid, bis (2-methyl propyl) ester (BDCe fraction). BDCe fraction was evaluated for the antiproliferative potential against human osteosarcoma MG-63, human neuroblastoma IMR-32, and human lung carcinoma A549 cell lines by MTT assay and exhibited GI 50 values of 37.53 μM, 56.05 μM, and 47.12 μM, respectively. In MG-63 cells, the BDCe fraction increased the level of ROS and simultaneously decreased the mitochondria membrane potential (MMP) potential by arresting cells at the G 0 /G 1 phase, suggesting the initiation of apoptosis. Western blotting analysis revealed the upregulation of p53, caspase3, and caspase9 while the expressions of p-NF-κB, p-Akt and Bcl-xl were decreased. RT-qPCR studies also showed upregulation in the expression of p53 and caspase3 and downregulation in the expression of CDK2, Bcl-2 and Cyclin E genes. Molecular docking analysis displayed the interaction between BDCe fraction with p53 (-151.13 kcal/mol) and CDK1 (-133.96 kcal/mol). The results of the present work suggest that the BDCe fraction has chemopreventive properties against osteosarcoma (MG-63) cells through the induction of cell cycle arrest and apoptosis via Akt/NF-κB/p53 pathways. This study contributes to the understanding of the utilization of BDCe fraction in osteosarcoma treatment.

Non-small-cell lung cancer (NSCLC) is the most common form of lung cancer, which is a leading cause of cancer-related deaths worldwide. Berberine is an isoquinoline alkaloid that is commercially available for use as a supplement for the treatment of diabetes and cardiovascular diseases. However, the therapeutic benefits of berberine are limited by its extremely low bioavailability and toxicity at higher doses. Increasing evidence suggests that the incorporation of drug compounds in liquid crystal nanoparticles provides a new platform for the safe, effective, stable, and controlled delivery of the drug molecules. This study aimed to formulate an optimized formulation of berberine-phytantriol-loaded liquid crystalline nanoparticles (BP-LCNs) and to investigate the in vitro anti-cancer activity in a human lung adenocarcinoma A549 cell line. The BP-LCN formulation possessing optimal characteristics that was used in this study had a favorable particle size and entrapment efficiency rate (75.31%) and a superior drug release profile. The potential mechanism of action of the formulation was determined by measuring the mRNA levels of the tumor-associated genes PTEN , P53 , and KRT18 and the protein expression levels with a human oncology protein array. BP-LCNs decreased the proliferation, migration, and colony-forming activity of A549 cells in a dose-dependent manner by upregulating the mRNA expression of PTEN and P53 and downregulating the mRNA expression of KRT18 . Similarly, BP-LCNs also decreased the expression of proteins related to cancer cell proliferation and migration. This study highlights the utility of phytantriol-based LCNs in incorporating drug molecules with low GI absorption and bioavailability to increase their pharmacological effectiveness and potency in NSCLC.

Introduction: Psoriasis is a chronic multifactorial inflammatory disease that affects 3% of people worldwide. Ustekinumab is a selective anti-IL-12/23 biologic that alleviates psoriasis, and curcumin is a natural, effective dietary turmeric extract applied to treat numerous diseases through its antioxidant and anti-inflammatory effects., Objective: The current study evaluated the therapeutic effects of curcumin and ustekinumab cotherapy (CUC) on imiquimod (IQ)-induced psoriasis in a rat model., Materials and Methods: Twenty rats were divided into four groups, G1 (control group), G2 (IQ-treated group), G3 (IQ + ustekinumab), and G4 (IQ + CUC). Clinical, histopathological (HP), immunohistochemical (IHC), antioxidant, and biochemical investigations evaluated the efficacy of these drugs for treating IQ induced-psoriasis., Results: Rats of G2 exhibited clinical signs of psoriatic skin lesions (erythema, scaling, and skin thickening) with epidermal changes (acanthosis and parakeratosis). Additionally, the biochemical analysis revealed significant ( p  < 0.05) reductions in the levels of antioxidant biomarkers (SOD, GPx, and CAT) with significant ( p  < 0.05) elevations in psoriasis-related cytokines (TNF-α, IL-17A, IL-12P40, and IL-23). In contrast, CUC alleviated the psoriatic changes in G4 better than ustekinumab monotherapy in G3., Conclusions: Ustekinumab inhibits the inflammatory cytokines IL-12P40 and IL-23, while curcumin has antioxidant effects (increasing SOD, GPx, and CAT levels) with anti-inflammatory effects (decreasing the proinflammatory cytokine TNF-α and IL-17). Therefore, CUC could be an excellent cost-effective regimen that can improve the treatment of psoriasis by the synergistic effects of CUC.HighlightsIQ-induces psoriasis by elevating TNF-α, IL-17A, IL-12, and IL-23 and decreasing GPx, SOD, and CATUstekinumab exhibits anti-inflammatory effects by inhibiting IL-12 and IL-23Curcumin inhibits TNF-α and IL-17A, and increases GPx, SOD, and CAT levelsCUC mitigates psoriasis by synergistic antioxidant and anti-inflammatory effectsCUC inhibits TNF-α, IL-17A, IL-12, and IL-23 and increases GPx, SOD, and CAT levels.

Acinetobacter baumannii has recently been increasing as an aggressive pathogen in immunocompromised persons. In the present study, we determined the in vitro antibacterial and anti-biofilm activity of thymoquinone (TQ) against A. baumannii . A liposomal formulation of TQ (Lip-TQ) was prepared and its therapeutic potential was investigated in the treatment of A. baumannii infection in immunocompromised mice. Leukopenia was induced in mice by injecting cyclophosphamide (CYP) at a dose of 200 mg/kg and the leukopenic mice were infected with 1 × 10 6 CFUs of A. baumannii . The effectiveness of free TQ or Lip-TQ against A. baumannii infection was assessed by analyzing the survival rate and bacterial burden. Moreover, the efficacy of Lip-TQ was also studied by examining the systemic inflammatory markers and the histological changes in the lung tissues. The results showed that the mice in the group treated with Lip-TQ at a dose of 10 mg/kg exhibited a 60% survival rate on day 40 post-infection, whereas all the mice treated with free TQ at the same dose died within this duration. Likewise, the lowest bacterial burden was found in the lung tissue of mice treated with Lip-TQ (10 mg/kg). Besides, Lip-TQ treatment remarkably alleviated the infection-associated inflammation, oxidative stress, and histological changes in the lung tissues. Based on the findings of the present study, we recommend considering Lip-TQ as a valuable therapeutic formulation in the treatment of A. baumannii -associated pneumonia in immunocompromised subjects.

The mortality and morbidity rates for prostate cancer have recently increased to alarming levels, rising higher than lung cancer. Due to a lack of drug targets and molecular probes, existing theranostic techniques are limited. Human LIN28A and its paralog LIN28B overexpression are associated with a number of tumors resulting in a remarkable increase in cancer aggression and poor prognoses. The current review aims to highlight recent work identifying the key roles of LIN28A and LIN28B in prostate cancer, and to instigate further preclinical and clinical research in this important area.

Celery ( Appium graveolens L.) and parsley ( Petroselinum crispum (Mill.) Fuss) are herbs utilized in the everyday diet as spices and culinary flavorings, often used in the chemical and medicinal industries. Despite the knowing benefits of different plants from the Apiaceae family, their chemical composition is closely associated with various extrinsic factors. Environmental loading with trace elements (TEs) can modify a plant's metabolic pathways, change bioactive compounds production, cause plant pollution, and consequently provoke human health issues. Therefore, we established this research aiming to unravel the linkage between TEs accumulation and phenolic status in celery and parsley. Higher As, Cd, and Ni levels were observed in celery, which was followed by greater DPPH ∙ radical scavenging activity and higher coumarins content. Contrary, parsley accumulated chromium to a greater extent, was richer in flavonoids, apigenin, and its glucosides. No significant difference between species was found in total phenolic contents, where ferulic and chlorogenic acid dominated in both species. A direct relationship between TEs and selected secondary metabolites was proven by the standardized major axis model. Besides abundant bioactive compounds, analyzed plant species showed a moderate hazard index in the children population, since the hazard index was higher than 1. Therefore, future perspectives should be turned towards the production of genotypes with a lower potential for toxic elements accumulation, so the health benefits of plant food will be more prominent.

Bronchial asthma (BA) is a heterogeneous allergic respiratory disease with diverse inflammatory symptoms, pathology, and responses to treatment. Thyme is a natural product which is consisted of multiple phenolic compounds of therapeutic significance for treatment of cough and bronchitis. This study evaluated the efficacy of thyme oil against ovalbumin (OVA)-induced BA in an experimental rabbit model. Forty male rabbits were divided into four equal groups [control group (G1), OVA (G2), thyme oil (G3), and OVA plus thyme oil (G4)]. Animals were treated for 30 days, and clinical, histopathological (HP), histochemical (HC), immunohistochemical (IHC), morphometric, biochemical and flow cytometry methods were performed, followed by statistical analysis. All used methods revealed normal structure of the lung tissues in rabbits of G1 and G3. In contrast, the clinical examination of G2 rabbits revealed an obvious increase in the respiratory rate, sneezing and wheezing, whereas the HP, HC and IHC techniques exhibited substantial inflammatory changes in the peribronchio-vascular lung tissues with thinning, degeneration, apoptosis (using the TUNEL assay), necrosis, and shedding of the airway epithelium. Furthermore, the morphometric results confirmed significant increases in the numbers of inflammatory cells, goblet cells, eosinophils and apoptotic cells from (12, 0, 2, 2 cells) to (34,10, 16, 18 cells) respectively, as well as the area percentage of collagen fiber deposition and immunoexpression of eotaxin-1/10 high power fields. Additionally, the biochemical results revealed significant increases in the serum levels of TSLP, IL-4, IL-5, IL-9, IL-13, IgE and eotaxin-1 cytokines from (140, 40, 15, 38, 120, 100, 48) pg./ml to (360, 270, 130, 85, 365, 398, 110) pg./ml respectively, while analysis of ROS by flow cytometry revealed remarkable oxidative stress effects in G2 rabbits. On the other hand, treatment of rabbits with thyme oil in G4 substantially alleviated all OVA-induced alterations. Overall, our findings indicate for the first time that thyme oil can ameliorate OVA-induced BA via its immunomodulatory, anti-inflammatory, antiapoptotic, and antioxidant effects on the lung tissues of rabbits., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Diabetes epidemiological quantities are demonstrating one of the most important communities' health worries. The essential diabetic difficulties are including cardiomyopathy, nephropathy, inflammation, and retinopathy. Despite developments in glucose decreasing treatments and drugs, these diabetic complications are still ineffectively reversed or prohibited. Several signaling and molecular pathways are vital targets in the new therapies of diabetes. This review assesses the newest researches about the key molecules and signaling pathways as targets of molecular pharmacology in diabetes and diseases related to it for better treatment based on molecular sciences. The disease is not cured by current pharmacological strategies for type 2 diabetes. While several drug combinations are accessible that can efficiently modulate glycemia and mitigate long-term complications, these agents do not reverse pathogenesis, and in practice, they are not established to modify the patient's specific molecular profiling. Therapeutic companies have benefited from human genetics. Genome exploration, which is agnostic to the information that exists, has revealed tens of loci that impact glycemic modulation. The physiological report has begun to examine subtypes of diseases, illustrate heterogeneity and propose biochemical therapeutic pathways., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The purpose of this review is to highlight recent scientific developments and provide an overview of virus self-assembly and viral particle dynamics. Viruses are organized supramolecular structures with distinct yet related features and functions. Plant viruses are extensively used in biotechnology, and virus-like particulate matter is generated by genetic modification. Both provide a material-based means for selective distribution and delivery of drug molecules. Through surface engineering of their capsids, virus-derived nanomaterials facilitate various potential applications for selective drug delivery. Viruses have significant implications in chemotherapy, gene transfer, vaccine production, immunotherapy and molecular imaging., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (© 2021 The authors.)

Middle East respiratory syndrome (MERS) is a lethal respiratory disease with its first case reported back in 2012 (Jeddah, Saudi Arabia). It is a novel, single-stranded, positive-sense RNA beta coronavirus (MERS-CoV) that was isolated from a patient who died from a severe respiratory illness. Later, it was found that this patient was infected with MERS. MERS is endemic to countries in the Middle East regions, such as Saudi Arabia, Jordan, Qatar, Oman, Kuwait and the United Arab Emirates. It has been reported that the MERS virus originated from bats and dromedary camels, the natural hosts of MERS-CoV. The transmission of the virus to humans has been thought to be either direct or indirect. Few camel-to-human transmissions were reported earlier. However, the mode of transmission of how the virus affects humans remains unanswered. Moreover, outbreaks in either family-based or hospital-based settings were observed with high mortality rates, especially in individuals who did not receive proper management or those with underlying comorbidities, such as diabetes and renal failure. Since then, there have been numerous reports hypothesising complications in fatal cases of MERS. Over the years, various diagnostic methods, treatment strategies and preventive measures have been strategised in containing the MERS infection. Evidence from multiple sources implicated that no treatment options and vaccines have been developed in specific, for the direct management of MERS-CoV infection. Nevertheless, there are supportive measures outlined in response to symptom-related management. Health authorities should stress more on infection and prevention control measures, to ensure that MERS remains as a low-level threat to public health.

Research Background: From ancient times plants have been used for medicinal purposes against various ailments. In the modern era, plants are a major source of drugs and are an appealing drug candidate for the anticancer therapeutics against various molecular targets. Here we tested methanolic extract of dry leaves of Tamarix articulata for anticancer activity against a panel of hepatocellular carcinoma cells., Experimental Approach: Cell viability of hepatocellular carcinoma cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay after a dose-dependent treatment with the extract of T. articulata. Phase-contrast microscopy and 4՛,6-diamidino-2-phenylindole (DAPI) staining served to analyse cellular and nuclear morphology. Immunoblotting was performed to determine the expression of proteins associated with autophagy, apoptosis and cell cycle. However, flow cytometry was used for the quantification of apoptotic cells and the analysis of cells in different phases of the cycle after the treatment with various doses of T. articulata . Additionally, acridine orange staining and 2՛,7՛-dichlorofluorescein diacetate (DCFH-DA) dye were used to analyse the quantification of autophagosomes and reactive oxygen species., Results and Conclusion: Our results demonstrate that T. articulata methanolic extract exhibits promising antiproliferative activity with IC 50 values (271.1±4.4), (298.3±7.1) and (336.7±6.1) µg/mL against hepatocellular carcinoma HepG2, Huh7D12 and Hep3B cell lines, respectively. Mechanistically, we found that T. articulata methanolic extract induces cell death by activating apoptosis and autophagy pathways. First, T. articulata methanolic extract promoted autophagy, which was confirmed by acridine orange staining. The immunoblotting analysis further confirmed that the extract at higher doses consistently induced the conversion of LC3I to LC3II form with a gradual decrease in the expression of autophagy substrate protein p62. Second, T. articulata methanolic extract promoted reactive oxygen species production in hepatocellular carcinoma cells and activated reactive oxygen species-mediated apoptosis. Flow cytometry and immunoblotting analysis showed that the plant methanolic extract induced dose-dependent apoptosis and activated proapoptotic proteins caspase-3 and PARP1. Additionally, the extract triggered the arrest of the G 0 /G 1 phase of the cell cycle and upregulated the protein expression of p27/Kip and p21/Cip, with a decrease in cyclin D1 expression in hepatocellular carcinoma cells., Novelty and Scientific Contribution: The current study demonstrates that T. articulata methanolic extract exhibits promising anticancer potential to kill tumour cells by programmed cell death type I and II mechanisms and could be explored for potential drug candidate molecules to curtail cancer in the future., Competing Interests: CONFLICT OF INTEREST The authors declare that they have no conflict of interest.

In the present study, we investigated the activity of free thymoquinone (TQ) or liposomal thymoquinone (Lip-TQ) in comparison to standard antibiotic amoxicillin (AMX) against the drug-sensitive and drug-resistant Acinetobacter baumannii . A liposomal formulation of TQ was prepared and characterized and its toxicity was evaluated by analyzing the hematological, liver and kidney function parameters. TQ was effective against both drug-sensitive and drug-resistant A. baumannii as shown by the findings of drug susceptibility testing and time kill kinetics. Moreover, the therapeutic efficacy of TQ or Lip-TQ against A. baumannii was assessed by the survival rate and the bacterial load in the lung tissues of treated mice. The mice infected with drug-sensitive A. baumannii exhibited a 90% survival rate on day 30 post treatment with Lip-TQ at a dose of 10 mg/kg, whereas the mice treated with AMX (10 mg/kg) had a 100% survival rate. On the other hand, the mice infected with drug-resistant A. baumannii had a 70% survival rate in the group treated with Lip-TQ, whereas AMX was ineffective against drug-resistant A. baumannii and all the mice died within day 30 after the treatment. Moreover, Lip-TQ treatment effectively reduced the bacterial load in the lung tissues of the mice infected with the drug-sensitive and drug-resistant A. baumannii . Moreover, the blood of the mice treated with Lip-TQ had reduced levels of inflammation markers, leukocytes and neutrophils. The results of the present study suggest that Lip-TQ may prove to be an effective therapeutic formulation in the treatment of the drug-sensitive or drug-resistant A. baumannii infection as well.

The COVID-19 pandemic continues to endanger world health and the economy. The causative SARS-CoV-2 coronavirus has a unique replication system. The end point of the COVID-19 pandemic is either herd immunity or widespread availability of an effective vaccine. Multiple candidate vaccines - peptide, virus-like particle, viral vectors (replicating and nonreplicating), nucleic acids (DNA or RNA), live attenuated virus, recombinant designed proteins and inactivated virus - are presently under various stages of expansion, and a small number of vaccine candidates have progressed into clinical phases. At the time of writing, three major pharmaceutical companies, namely Pfizer and Moderna, have their vaccines under mass production and administered to the public. This review aims to investigate the most critical vaccines developed for COVID-19 to date.

The aim of present study is to investigate the role of 6-gingerol in ameliorating the renal injury in streptozotocin (STZ)-induced diabetic rats. The diabetes was induced by using a single dose of freshly prepared STZ (55 mg/kg body weight) intraperitoneally which causes the degeneration of pancreatic Langerhans islet β-cells. The diabetic rats were treated with oral gavage of 6-gingerol (10 mg/kg b.w.). The treatment plan was continued for 8 weeks successively and the body weight and fasting blood glucose levels were weekly checked. The biochemical parameters like lipid profile, kidney profile, antioxidant enzyme levels, lipid peroxidation and anti-inflammatory marker levels were investigated after the treatment plant. The pathological condition of kidneys was examined by haematoxylin-eosin (H&E) staining besides this analysis of NF- κ B protein expression by immuno-histochemistry was performed. Some of the major parameters in diabetes control vs. normal control were reported as fasting blood glucose (234 ± 10 vs. 102 ± 8 mg/dL), serum creatinine (109.7 ± 7.2 vs. 78.9 ± 4.5 μmol/L) and urea (39.9 ± 1.8 vs. 18.6 mg/dL), lipid profile levels were significantly enhanced in diabetic rats. Moreover, diabetic rats were marked with decreased antioxidant enzyme levels and increased inflammatory markers. Treatment with 6-gingerol significantly restored the fasting blood glucose level, hyperlipidaemia, Malondialdehyde ( MDA ) and inflammatory marker levels, NF- κ B protein expression and augmented the antioxidant enzyme levels in the kidneys of diabetic rats. The kidney damage was significantly normalized by the treatment of 6-gingerol and it provides an evidence that this novel compound plays a significant role in the protection of kidney damage. These findings demonstrate that 6-gingerol reduces lipid parameters, inflammation and oxidative stress in diabetic rats, thereby inhibiting the renal damage. Our results demonstrate that use of 6-gingerol could be a novel therapeutic approach to prevent the kidney damage associated with the diabetes mellitus.

Tamarix articulata (TA) is a wild halophytic plant growing in extremely harsh environmental conditions in the deserts of Saudi Arabia. Evaluating the protective effect of the methanolic extract of different parts (fresh and dry leaves, stem, and root) of TA was determined by MTT assay using Hs27 skin fibroblasts as the cellular model. The study was designed and conducted in two sets. The first set assesses the toxicity profile of TA extracts in both concentration- and time-dependent ways on Hs27 cells. Our MTT results showed that methanolic extracts from all four parts of TA at varying doses (27.5, 55, 110, and 220  μ g/mL) display negligible toxicity when exposed for 4 h. However, exposure of Hs27 cells to varying doses of all four TA extracts for 24 and 48 h promotes significant 23%, 24%, 26%, and 25% ( p < 0.05) and 35%, 36%, 39%, and 41% ( p < 0.05) cell toxicity at 220  μ g/mL of all four TA extracts compared to untreated control cells. To evaluate the protection offered by TA extracts against H₂O₂, we perform a second set of experiments to preincubate Hs27 cells with the TA extracts in both dose- and time-dependent way. This is followed by 300  μ M hydrogen peroxide- (H₂O₂-) mediated oxidative insult for 1 h. Using MTT assay, we found that methanolic extracts of TA at different time points (4, 24, and 48 h) and higher doses (220  μ g/mL) provide significant protection in cell viability when challenged with H 2 O 2 -induced oxidative stress in Hs27 cells. The protective effect was more pronounced at 48 h and 220  μ g/mL and the amounts were 39%, 41%, 41%, and 44% for stem, root, fresh leaf, and dry leaf TA extracts ( p < 0.05), respectively, compared to untreated cells (2-4%). Collectively, the current study demonstrates that methanolic extracts of TA contain potential bioactive compounds and offer significant protection against H 2 O 2 -mediated oxidative stress in Hs27 skin fibroblasts., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Abdullah M. Alnuqaydan.)

Background: Poisoning has become a widespread and dangerous phenomenon worldwide. The purpose of our study was to determine and analyze the pattern of poisoning cases induced with food, drugs, and chemicals reported to the Department of Environmental and Occupational Health in Qassim province in the Kingdom of Saudi Arabia. The study also evaluated the correlation of demographic variables such as age, type of toxicity and geographical distribution associated with poisoning in Qassim province., Methods: This retrospective cross-sectional study was performed on 381 cases of poisoning. The data was collected from Jan 2017 to Dec 2017 and revealed that out of 381 cases, 120 have food poisoning (65 % females and 35 % males), 180 have drug poisoning (55.56 % females and 44.44 % males), whereas 81 cases have chemical poisoning (41.98 % female and 58.02 % male). Data were statistically analyzed using SPSS/PC statistical package. The study revealed that the most common agents involved in acute poisoning were drugs (47.25 %), especially analgesics such as Paracetamol (Acetaminophen), followed by antipsychotic drugs. Food poisoning was the second acute poisoning with (31.40 %). Finally, chemical poisoning involved in acute poisoning with 21.20 % of cases reported household products accomplished strongest bleach (chlorines)(Clorox®) and insecticides were the secondary source for chemical poisoning., Competing Interests: The authors report no declarations of interest., (© 2020 The Author(s).)

Owing to extremely high salinity and harsh environmental conditions, T. articulata is one of the most abundant wild plants growing in the deserts of Saudi Arabia. Such plants may contain novel compounds to display promising biological activities. Here, in this study, we evaluate the biological activities of methanolic extracts of fresh leaves, dry leaves, stem, and roots of T. articulata. The antioxidant activity was determined by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and total phenolic and flavonoid content were determined using standard colorimetric methods. Whereas antimicrobial and ant-proliferative activities were determined by standard well-diffusion and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) methods, respectively. Our results demonstrate that all methanolic extracts of T. articulata showed antioxidant activity, however, the methanolic extract of dry leaves exhibits promising antioxidant effect with IC₅₀ value 49.08 ± 1.98, which was strongly supported by total phenolic (409.92 ± 6.03 mg GAE/g DW) and flavonoid (177.71 mg QE/g DW) content. Although, antimicrobial activity was also exhibited by all the methanolic extracts, however, methanolic extract of dry leaves exhibits promising antimicrobial activity in Gram-positive bacteria Staphylococcus epidemidis. Furthermore , MTT assay revealed that all methanolic extracts exhibit antiproliferative activity in MCF-7 (breast cancer) and RKO (colorectal cancer) cells with IC₅₀ values ranges from 219 ± 5.112 µg/ml to 253 ± 5.231 µg/ml and 220 ± 4.330 µg/ml to 325 ± 6.213 µg/ml, respectively. However, the most promising antiproliferative effect was displayed by methanolic extract of dry leaves with IC₅₀ values 219 ± 5.112 µg/ml and 220 ± 4.330 µg/ml, respectively . In summary, these findings provide evidence that T. articulata has promising biological activities and can be used for many pharmaceutical activities in the future., Competing Interests: 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., (© 2020 Published by Elsevier B.V. on behalf of King Saud University.)

MicroRNAs are a class of short, non-coding RNAs that play a crucial role in normal physiology by attenuating translation or targeting messenger RNAs for degradation. Deregulation of miRNAs disturbs key molecular events in interconnected processes such as cell proliferation, tumor angiogenesis, self-renewal, apoptosis, metastasis and epithelial to mesenchymal transition. This process initiates, promotes and develops the pathophysiology of cancer. The modulation of miRNAs results in epigenetic changes in the genome, which eventually leads to cancer. Targeting deregulated miRNAs by natural products derived from plants is an ideal strategy to combat tumorigenesis. Owing to their fewer side effects, natural products have been used as chemotherapeutic agents against various cancers. These natural products modulate the dysregulated signaling pathways by downregulating the oncogenic miRNAs which play a crucial role in the development of tumorigenesis and maintain a fine balance of tumor suppressor miRNAs. This review article aims to highlight the key modifications of miRNAs which lead to tumorigenesis and the chemotherapeutic potential of natural products by targeting miRNAs and their possible mechanism of inhibition for developing an effective anti-cancer agent(s). They will have less damaging effects on normal cells for future chemotherapeutics., Competing Interests: None., (AJTR Copyright © 2020.)

The development of chemo-resistance against 5-fluorouracil (5-FU) in tumor cells is one of the main debacles in colorectal cancer (CRC) patients. A recent combination of 5-FU with oxaliplatin or cetuximab drastically improves the survival rate in CRC patients; however, the toxicity issue cannot be evaded completely. Thus, searching for novel drug combinations with high specificity and low toxicity is seemingly important. Owing to the less undesirable effects of natural products on normal cells, here we investigated the synergistic antitumor effect of withaferin-A (WA) in combination with 5-FU. Our results demonstrate that the combination of WA and 5-FU induces a significant antiproliferative effect and modulates endoplasmic reticulum (ER) stress in favor of cell death in colorectal cancer (CRC) cells. Mechanistically, the combination upregulates the expression of ER stress sensors (BiP, PERK, CHOP, ATF-4, and eIF2α) and executes PERK axis mediated apoptosis in CRC cells. Additionally, the combined treatment of WA and 5-FU mediated ER stress induces autophagy and apoptosis, which were confirmed by immunoblotting, acridine orange (AO) staining and annexin-V FITC by flow cytometry. In contrast, inhibition of ER stress with salubrinal significantly decreases both autophagic and apoptotic cell populations. Moreover, pharmacological inhibition of either autophagy or apoptosis by their respective inhibitors 3-methyladenine (3-MA) or carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoro-methyl ketone (Z-VAD-FMK) decreases their respective population of cells but could not affect either of the population significantly. Finally, the combination attenuates the expression of β-catenin pathway associated proteins and arrests cell cycle at the G 2 M phase in CRC cells. In summary, the combination of WA and 5-FU decreases cell viability by inducing ER stress-mediated induction of autophagy and apoptosis, inhibiting the β-catenin pathway and arresting the cell cycle at a G 2 M phase in CRC cells., Competing Interests: None., (AJCR Copyright © 2020.)

Background: Tamarix Articulata (T. articulata), commonly known as Tamarisk or Athal in Arabic region, belongs to the Tamaricaece species. It is an important halophytic medicinal plant and a good source of polyphenolic phytochemical(s). In traditional medicines, T. articulata extract is commonly used, either singly or in combination with other plant extracts against different ailments since ancient times., Methods: Electronic database survey via Pubmed, Google Scholar, Researchgate, Scopus and Science Direct were used to review the scientific inputs until October 2018, by searching appropriate keywords. Literature related to pharmacological activities of T. articulata, Tamarix species, phytochemical analysis of T. articulata, biological activities of T. articulata extracts. All of these terms were used to search the scientific literature associated with T. articulata; the dosage of extract, route of administration, extract type, and in-vitro and in-vivo model., Results: Numerous reports revealed that T. articulata contains a wide spectrum of phytochemical(s), which enables it to have a wide window of biological properties. Owing to the presence of high content of phytochemical compounds like polyphenolics and flavonoids, T. articulata is a potential source of antioxidant, anti-inflammatory and antiproliferative properties. In view of these pharmacological properties, T. articulata could be a potential drug candidate to treat various clinical conditions including cancer in the near future., Conclusion: In this review, the spectrum of phytochemical(s) has been summarized for their pharmacological properties and the mechanisms of action, and the possible potential therapeutic applications of this plant against various diseases discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The in vitro safety and antioxidant potential of Calendula officinalis flower head extracts was investigated. The effect of different concentrations (0.125, 0.5, 1.0, 2.0 and 5.0% (v/v)) of Calendula extracts on human skin cells HaCaT in vitro was explored. Doses of 1.0% (v/v) (0.88 mg dry weight/mL) or less showed no toxicity. Cells were also exposed to the Calendula extracts for either 4, 24 or 48 h before being exposed to an oxidative insult (hydrogen peroxide H2 O2 ) for 1 h. Using the MTT cytotoxicity assay, it was observed that two independent extracts of C. officinalis gave time-dependent and concentration-dependent H2 O2 protection against induced oxidative stress in vitro using human skin cells. Pre-incubation with the Calendula extracts for 24 and 48 h increased survival relative to the population without extract by 20% and 40% respectively following oxidative challenge. The antioxidant potential of the Calendula extracts was confirmed using a complimentary chemical technique, the DPPH(●) assay. Calendula extracts exhibited free radical scavenging abilities. This study demonstrates that Calendula flower extracts contain bioactive and free radical scavenging compounds that significantly protect against oxidative stress in a human skin cell culture model., (Copyright © 2014 John Wiley & Sons, Ltd.)