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COVID-19 caused by the SARS-CoV-2 virus is widespread in all regions, and it disturbs host immune system functioning leading to extreme inflammatory reaction and hyperactivation of the immune response. Kabasura Kudineer (KSK) is preventive medicine against viral infections and a potent immune booster for inflammation-related diseases. We hypothesize that KSK and KSK similar plant compounds, might prevent or control the COVID-19 infection in the human body. 1,207 KSK and KSK similar compounds were listed and screened via the Swiss ADME tool and PAINS Remover; 303 compounds were filtered including active and similar drug compounds. The targets were retrieved from similar drugs of the active compounds of KSK. Finally, 573 genes were listed after several screening steps. Next, network analysis was performed to finalize the potential target gene: construction of protein-protein interaction of 573 genes using STRING, identifying top hub genes in Cytoscape plug-ins (MCODE and cytoHubba). These ten hub genes play a crucial role in the inflammatory response. Target-miRNA interaction was also constructed using the miRNet tool to interpret miRNAs of the target genes and their functions. Functional annotation was done via DAVID to gain a complete insight into the mechanism of the enriched pathways and other diseases related to the given target genes. In Molecular Docking analysis, IL10 attained top rank in Target-miRNA interaction and also the gene formed prominent exchanges with an excellent binding score (> = -8.0) against 19 compounds. Among them, Guggulsterone has an acute affinity score of -8.8 for IL10 and exhibits anti-inflammatory and immunomodulatory properties. Molecular Dynamics simulation study also performed for IL10 and the interacting ligand compounds using GROMACS. Finally, Guggulsterone will be recommended to enhance immunity against several inflammatory diseases, including COVID19.

Previous studies reported disrupted hepatic function and structure following the administration of cyclosporine A (CsA) in humans and animals. Recently, we found that avocado seeds (AvS) ameliorated CsA-induced nephrotoxicity in rats. As a continuation, herein we checked whether AvS could also attenuate CsA-induced hepatotoxicity in rats. Subcutaneous injection of CsA (5 mg/kg) for 7 days triggered hepatotoxicity in rats, as indicated by liver dysfunction, redox imbalance, and histopathological changes. Oral administration of 5% AvS powder for 4 weeks ameliorated CsA-induced hepatotoxicity, as evidenced by (1) decreased levels of liver damage parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin), (2) resumed redox balance in the liver (reduced malondialdehyde (MDA) and increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), (3) downregulated hepatic expression of endoplasmic reticulum (ER) stress-related genes (X-box binding protein 1 (XBP1), binding immunoglobulin protein (BIP), C/EBP homologous protein (CHOP)), and apoptosis-related genes (Bax and Casp3), (4) upregulated expression of the anti-apoptotic gene Bcl2, (5) reduced DNA damage, and (6) improved liver histology. These results highlight the ability of AvS to ameliorate CsA-induced hepatotoxicity via the inhibition of oxidative stress and proapoptotic ER stress.

Contradictory results were obtained regarding the effects of extracellular vesicles such as exosomes (EXOs) on diabetes and diabetic nephropathy (DN). Some studies showed that EXOs, including milk EXOs, were involved in the pathogenesis of DN, whereas other studies revealed ameliorative effects. Compared to other animals, camel milk had unique components that lower blood glucose levels. However, little is known regarding the effect of camel milk and its EXOs on DN. Thus, the present study was conducted to evaluate this effect on a rat model of DN induced by streptozotocin. Treatment with camel milk and/or its EXOs ameliorated DN as evidenced by (1) reduced levels of kidney function parameters (urea, creatinine, retinol-binding protein (RBP), and urinary proteins), (2) restored redox balance (decreased lipid peroxide malondialdehyde (MDA) and increased the activity of antioxidants enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)), (3) downregulated expression of DN-related genes (transforming growth factor-beta 1 (TGFβ1), intercellular adhesion molecules 1 (ICAM1), and transformation specific 1 (ETS1), integrin subunit beta 2 (ITGβ2), tissue inhibitors of matrix metalloproteinase 2 (TIMP2), and kidney injury molecule-1 (KIM1)), and (4) decreased renal damage histological score. These results concluded that the treatment with camel milk and/or its EXOs could ameliorate DN with a better effect for the combined therapy.

Globally, iron-deficiency anemia (IDA) remains a major health obstacle. This health condition has been identified in 47% of pre-school students (aged 0 to 5 years), 42% of pregnant females, and 30% of non-pregnant females (aged 15 to 50 years) worldwide according to the WHO. Environmental and genetic factors play a crucial role in the development of IDA; genetic testing has revealed the association of a number of polymorphisms with iron status and serum ferritin. The current study aims to reveal the association of TMPRSS6 rs141312 and BMP2 rs235756 with the iron status of females in Saudi Arabia. A cohort of 108 female university students aged 18-25 years was randomly selected to participate: 50 healthy and 58 classified as iron deficient. A 3-5 mL sample of blood was collected from each one and analyzed based on hematological and biochemical iron status followed by genotyping by PCR. The genotype distribution of TMPRSS6 rs141312 was 8% (TT), 88% (TC) and 4% (CC) in the healthy group compared with 3.45% (TT), 89.66% (TC) and 6.89% (CC) in the iron-deficient group (P = 0.492), an insignificant difference in the allelic distribution. The genotype distribution of BMP2 rs235756 was 8% (TT), 90% (TC) and 2% (CC) in the healthy group compared with 3.45% (TT), 82.76% (TC) and 13.79% (CC) in iron-deficient group (P = 0.050) and was significantly associated with decreased ferritin status (P = 0.050). In addition, TMPRSS6 rs141312 is significantly (P<0.001) associated with dominant genotypes (TC+CC) and increased risk of IDA while BMP2 rs235756 is significantly (P<0.026) associated with recessive homozygote CC genotypes and increased risk of IDA. Our finding potentially helps in the early prediction of iron deficiency in females through the genetic testing.

Few researches have explored the production of pharmaceuticals from aquatic plants. Therefore, this study explored, for the first time, the phytochemical composition and bioactivities of ten aquatic plants. Aquatic plant shoots from various Nile River canals were collected, dried, and ground for aqueous extract preparation. Phytochemical composition and antioxidant capacity were assessed using DPPH assays. Extracts were tested for antiparasitic, antibacterial, anti-biofilm, and anticancer activities through standard in vitro assays, measuring IC50 values, and evaluating mechanisms of action, including cell viability and high-content screening assays. The results showed that the aquatic plants were rich in pharmaceutical compounds. The antioxidant capacity of these extracts exceeded that of vitamin C. The extracts showed promising antiparasitic activity against pathogens like Opisthorchis viverrini and Plasmodium falciparum, with IC50 values between 0.7 and 2.5 µg/mL. They also demonstrated low MICs against various pathogenic bacteria, causing DNA damage, increased plasma membrane permeability, and 90% biofilm inhibition. In terms of anticancer activity, extracts were effective against a panel of cancer cell lines, with Ludwigia stolonifera exhibiting the highest efficacy. Its IC50 ranged from 0.5 µg/mL for pancreatic, esophageal, and colon cancer cells to 1.5 µg/mL for gastric cancer cells. Overall, IC50 values for all extracts were below 6 µg/mL, showing significant apoptotic activity, increased nuclear intensity, plasma membrane permeability, mitochondrial membrane permeability, and cytochrome c release, and outperforming doxorubicin. This study highlights the potential of aquatic plants as sources for new, safe, and effective drugs with strong antiparasitic, antibacterial, and anticancer properties.

Ischemic stroke poses a notable global public health challenge, with the Kingdom of Saudi Arabia (KSA) being no exception. This multifaceted condition is affected by a combination of factors, including hypertension, diabetes, and genetic influences. The purpose of the present study was to examine the linkage of long noncoding RNAs (such as ANRIL), plasminogen activator inhibitor-1 (PAI-1), and hepatocyte nuclear factor 1 alpha (HNF1α) gene variations with stroke. Leveraging a substantial cohort comprising both stroke patients and healthy individuals from KSA, our research revealed numerous uncommon genetic variations linked to an increased predisposition to stroke. This insight enhances our comprehension of stroke's genetic underpinnings and can be invaluable in formulating preventive measures, not only in KSA but also on a global scale. In this study we included 100 stroke patients and 100-120 healthy controls from Saudi population. We utilized the amplification refractory mutation system-PCR to genotype the chromosome 9p21 locus, the long noncoding RNA-ANRIL (lncRNA-ANRIL), Hepatocyte Nuclear Factor 1 alpha (HNF1α-A > C [p.I27L]) gene, and the plasminogen activator inhibitor-1 (PAI-1) gene to investigate the association of these gene variations with a stroke. Additionally, WES was performed for 10 stroke patients using the Illumina NovaSeq 6000 platform. Our investigation revealed significant associations between stroke patients and healthy controls concerning polymorphic variants of lncRNA-ANRIL (A > C), ANRIL (G > A), HNF1α-A > C, and PAI-1-4G > 5G genes (p < 0.05). Notably, the ANRIL rs1333048-GA genotype exhibited a strong connection with stroke susceptibility in both codominant (OR 2.29, RR 1.54, P < 0.007) and dominant (OR 1.83, RR 1.35, P < 0.034) models, while an overdominant inheritance model demonstrated a protective correlation (OR 0.42, RR 0.64, p < 0.004). Similarly, the ANRIL rs10757278-GG genotype was significantly associated with stroke susceptibility in the codominant (OR 2.80, RR 1.66, P < 0.004) and recessive (OR 3.14, RR 1.62, P < 0.0003) models, with the G allele also displaying a significant association. The HNF1α-TT genotype strongly correlated with stroke risk in the codominant (OR 18.36, RR 9.96, P < 0.048) and recessive (OR 22.14, RR 10.18, P < 0.034) models, with the HNF1α-T allele following a similar trend. The PAI-1-4G-5G genotype was also linked to stroke predisposition (OR 2.09, RR 1.34, P < 0.034) and an increased risk in the dominant model (OR 2.27, RR 1.43, P < 0.006). Furthermore, our study identified several novel and common gene variants in stroke patients through WES, including COL4A2, PSEN2, NOTCH3, and RNF2. Our findings underscore the significant role of genetic determinants in chromosome 9p21, the lncRNA-ANRIL, HNF1α-A > C (p.I27L), and PAI-1-4G > 5G genes in elevating the risk of stroke. Additionally, we report low, novel, and intermediate-genetic-risk variants in COL4A2, PSEN2, NOTCH3, and RNF2 through WES, emphasizing the need for further investigation in larger cohort studies.

The full-length BRCA1-associated RING domain 1 (BARD1) gene encodes a 777-aa protein. BARD1 displays a dual role in cancer development and progression as it acts as a tumor suppressor and an oncogene. Structurally, BARD1 has homologous domains to BRCA1 that aid their heterodimer interaction to inhibit the progression of different cancers such as breast and ovarian cancers following the BRCA1-dependant pathway. In addition, BARD1 was shown to be involved in other pathways that are involved in tumor suppression (BRCA1-independent pathway) such as the TP53-dependent apoptotic signaling pathway. However, there are abundant BARD1 isoforms exist that are different from the full-length BARD1 due to nonsense and frameshift mutations, or deletions were found to be associated with susceptibility to various cancers including neuroblastoma, lung, breast, and cervical cancers. This article reviews the spectrum of BARD1 full-length genes and its different isoforms and their anticipated associated risk. Additionally, the study also highlights the role of BARD1 as an oncogene in breast cancer patients and its potential uses as a prognostic/diagnostic biomarker and as a therapeutic target for cancer susceptibility testing and treatment.

Chronic lymphocytic leukemia (CLL) is an incurable malignancy of B-cells. In this study, bioinformatics analyses were conducted to identify possible pathogenic roles of CK2α, which is a protein encoded by CSNK2A1 , in the progression and aggressiveness of CLL. Furthermore, various computational tools were used to search for a competent inhibitor of CK2α from fungal metabolites that could be proposed for CLL therapy. In CLL patients, high-expression of CSNK2A1 was associated with early need for therapy (n = 130, p  < 0.0001) and short overall survival (OS; n = 107, p  = 0.005). Consistently, bioinformatics analyses showed CSNK2A1 to associate with/play roles in CLL proliferation and survival-dependent pathways. Furthermore, PPI network analysis identified interaction partners of CK2α (PPI enrichment p value = 1 × 10 –16 ) that associated with early need for therapy (n = 130, p  < 0.003) and have been known to heavily impact on the progression of CLL. These findings constructed a rational for targeting CK2α for CLL therapy. Consequently, computational analyses reported 35 fungal metabolites out of 5820 (filtered from 19,967 metabolites) to have lower binding energy (ΔG: − 10.9 to − 11.7 kcal/mol) and better binding affinity (Kd: 9.77 × 10 7  M −1 to 3.77 × 10 8  M −1 ) compared with the native ligand (ΔG: − 10.8, Kd: 8.3 × 10 7  M− −1 ). Furthermore, molecular dynamics simulation study established that Butyl Xanalterate-CK2α complex continuously remained stable throughout the simulation time (100 ns). Moreover, Butyl Xanalterate interacted with most of the catalytic residues, where complex was stabilized by more than 65% hydrogen bond interactions, and a significant hydrophobic interaction with residue Phe113. Here, high-expression of CSNK2A1 was implicated in the progression and poor prognosis of CLL, making it a potential therapeutic target in the disease. Butyl Xanalterate showed stable and strong interactions with CK2α, thus we propose it as a competitive inhibitor of CK2α for CLL therapy.

[This corrects the article DOI: 10.1371/journal.pone.0257895.].

There is a shortage in the experimental research directly comparing the effectiveness of different nanoparticles in boosting asparaginase (ASNase) activity. This study assessed the impact of various nanoparticles on enhancing ASNase activity, stability, and anticancer effects through immobilization. Escherichia coli ASNase was immobilized on different nanoparticles, and its efficiency was measured. The research included analyzing the enzyme’s secondary structure, stability, activity at different temperatures, kinetic parameters, shelf life, and activity in blood serum. The anticancer efficacy was determined by measuring the IC50. The study also investigated the anticancer mechanisms by examining the enzyme’s toxicity on cancer cells, focusing on apoptosis indicators like nuclear intensity, membrane permeability, mitochondrial membrane permeability, and cytochrome c release. Among the tested nanoparticles, nano chitosan yielded the best improvements. ASNase immobilized on nano chitosan reached 90% immobilization efficiency fastest among the studied nanoparticles, achieving this within 72 h, whereas other nanoparticles took 120 h. Immobilization modified ASNase’s secondary structure by increasing alpha helices and reducing random coils, with nanochitosan and magnetic iron oxide showing the most pronounced effects. Immobilized ASNase exhibited enhanced activity, stability across temperature (widest with nanochitosan, 25–65 °C), and a broader optimal pH range compared to the free enzyme, with a Km of 1.227 mM and a Vmax of 454.54 U/mg protein. Notably, the nano-chitosan-immobilized ASNase retained over 85% of its activity after 9 months of storage and maintained high activity in blood serum. This improved stability and activity translated into the highest anticancer activity (Lowest IC50) and was more effective than doxorubicin in disrupting cancer cell structures.