Atif Abdulwahab A. Oyouni

However, the cytotoxic and antioxidant properties of halophyteshave been previously reported, the underlying molecular mechanisms remain poorly understood. In the present study, we not only evaluate the cytotoxic and antioxidant potential of extracts from halophytic species but also, for the first time, elucidate their mechanistic mode of action using an integrated high-content screening and RT-PCR approach to verify apoptosis induction and the modulation of apoptosis-related signaling pathways. Phytochemical screening revealed a diverse array of secondary metabolites, with S. fruticosa and A. marina showing the richest compositions. Notably, these two species also exhibited exceptional antioxidant capacity, with IC₅₀ values (6.04 and 10.05 µg/mL, respectively) significantly outperforming ascorbic acid. More importantly, this study advances our understanding of the molecular mechanisms underlying the anticancer properties of these extracts. A. marina demonstrated remarkable cytotoxicity against MCF-7, HepG2, and HCT116 cancer cell lines (IC₅₀ < 0.17 µg/mL), accompanied by high selectivity indices (up to 1723.1), indicating a strong therapeutic window. Mechanistic investigations using high-content screen and RT-PCR revealed that the most active extracts induce apoptosis via mitochondrial dysfunction, evidenced by loss of mitochondrial membrane potential, increased plasma membrane permeability (up to 465%) y, and cytochrome c release (> 740%). Furthermore, gene expression profiling demonstrated significant upregulation of pro-apoptotic markers (BAX, Caspase-3), downregulation of anti-apoptotic BCL-2, and modulation of oncogenic and cell cycle regulatory pathways, including CDK1, Cyclin B1, p21, c-MYC, and PI3K/AKT/mTOR signaling. Hierarchical clustering grouped S. fruticosa, A. marina, and Atriplex halimus as the most potent extracts.

This study investigated the potential of Hermetia illucens (Black Soldier Fly) Larvae powder to mitigate malnutrition‐induced impairments in growth and immune function. Sixty male Wistar rats ( n = 15 per group) were assigned to four groups: control, malnourished, malnourished supplemented with H. illucens powder, and H. illucens ‐only. Supplementation was administered daily via oral gavage at 10 g/kg body weight for 21 days. Growth performance, food intake, and health scores were recorded. At the same time, immune function was assessed through lymphocyte proliferation, macrophage phagocytosis, antibody titers, and quantitative real‐time polymerase chain reaction analysis of immune‐related genes. Malnutrition markedly reduced final body weight (−36%), food intake (−36%), health scores (−67%), lymphocyte proliferation (−54%), phagocytic activity (−63%), antibody titers (−62%), and immune gene expression (−60%–74%) compared to controls ( p < 0.05). H. illucens supplementation improved these parameters to near‐control levels: body weight (+50%), lymphocyte proliferation (94% recovery), phagocytosis (98%), antibody titers (98%), and immune gene expression (90%–96% of control). Rats receiving H. illucens only showed slightly higher immune responses without adverse effects ( p > 0.05). The beneficial effects of H. illucens powder are likely linked to its bioactive components, including chitin and lauric acid, which support gut health, modulate inflammation, and enhance immune competence.

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Stroke is a health problem all over the world. It is a primary cause of disability and ranked number two death cause. In kingdom of Saudi Arabia KSA, the prevalence of stroke in the KSA estimated to be more than 40 per 100 thousand in 2021. The incidence of stroke is increasing in KSA. The risk factors for stroke are grouped into modifiable and nonmodifiable. The modifiable risk factors include diabetes, hyperlipidemia physical inactivity, and diet, whereas the nonmodifiable include sex, age, and race/ethnicity. Decreasing the modifiable risk factors reduces the burden of stroke in population. The long noncoding RNAs (LncRNAs) ANRIL is suggested as a biomarker and treatment target for stroke. The Transcription factor 7-like 2 (TCF7L2) has crucial roles in biological and pathological processes such as inflammation, metabolism, and atherosclerosis. In this study, we examined the associations of ANRIL rs1333045 C>T, CYP2C19*17 (C806T, rs12248560C>T, and TCF7L2 rs12255372 G>T with stroke in 100 stroke cases and 100 matched healthy controls from Tabuk population using the amplification refractory mutation system PCR (ARMS-PCR). Results indicated that the T allele of the ANRIL rs1333048 C>T was associated with stroke with Odd ratio (OR) = 1.73, P value-0.0067. Likewise, the GT genotype and the T allele of the TCF7L2 rs12255372 G>T were associated with stroke with OR = 2.14, P value = 0.01, and 1.9, P value = 0.004, respectively. In addition, the CT genotype and T allele of the CYP2C19*17 (rs12248560) C>T were also associated stroke with OR = 2, P value = 0.02 and OR = 2.3, P value = 0.002, respectively. We conclude that ANRIL rs1333045 C>T, CYP2C19*17 (C806T, rs12248560C>T, and TCF7L2 rs12255372 G>T are potential loci for susceptibility to stroke. This will assist in treatment and/or prevention of cerebrovascular disease.

Arthritic diseases are a significant global health challenge, highlighting the urgent need for innovative therapeutic strategies. Extracellular vesicles (EVs) have emerged as promising candidates for treating various intractable diseases. This review explores the therapeutic potential of engineered EVs in joint diseases, particularly in comparison to their parental stem cells. Recent research underscores the efficacy of EVs in treating joint diseases, especially Osteoarthritis (OA). We discuss EV engineering strategies aimed at overcoming the limitations of natural EVs. Data from preclinical trials, clinical studies, and in vitro and in vivo reports are analyzed to evaluate the effectiveness of EVs in treating joint conditions. In addition to their role in intercellular communication, EVs influence various biological processes crucial for bone remodeling, cartilage regeneration, immunomodulation, and inflammation control. EVs are rich in vital biomolecules such as proteins, microRNAs (miRNA), lipids, and nucleic acids, which enhance their therapeutic potential compared to parental stem cells. This understanding is key to developing targeted and effective engineered EVs for OA and other joint diseases. A comprehensive grasp of EV engineering and underlying mechanisms will pave the way for novel and efficient therapies for arthritic diseases and related conditions.This article is categorized under: Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Nanotechnology Approaches to Biology > Cells at the Nanoscale Biology‐Inspired Nanomaterials > Peptide‐Based Structures

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 K_m of 1.227 mM and a V_max 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.

Cervical Cancer remains a women’s health concern worldwide and ranks among the most prevalent cancers, particularly in developing countries. Many women are diagnosed with cervical cancer, with a substantial number succumbing to the disease even after the availability of vaccines and drugs. The tumour microenvironment often exhibits immune evasion, including suppression of T-cell activity and altered cytokine, impacting the efficacy of therapeutic interventions and highlighting the need for treatments to modulate the immune response. Despite efforts to promote HPV vaccination and regular screenings, it causes many deaths, underscoring the urgent need for continued research, healthcare access, and rapid drug development or repurposing. In this study, we identified various proteins involved in cervical cancer cell cycle regulation and DNA replication proteins, performed the multitargeted docking with an FDA-approved library, and identified Oxidopamine HBr as a multitargeted drug. Studies extended with pharmacokinetics and compared with the standard values followed by DFT, which supported the compound as a multitargeted inhibitor. Further, the docked complexes were taken for the interaction fingerprints, and it was identified that there are many 9 polar, 5 hydrophobic, 2 aromatic, and 2 basic residues. We extended our studies for 100ns MD Simulation in water, and the computations explored the deviation and fluctuations under 2Å and many intermolecular interactions; the same trajectory files were used for the MM\GBSA studies. All the studies have supported the Oxidopamine HBr as a cervical cancer multitargeted inhibitor—however, experimental studies are needed before human use.