ACTL6A: unraveling its prognostic impact and paving the way for targeted therapeutics in carcinogenesis.

Introduction: Increased Actin-like 6A (ACTL6A) expression is associated with various cancers, but its comprehensive investigation across different malignancies is lacking. We aimed to analyze ACTL6A as a potential oncogene and therapeutic target using bioinformatics tools. Methods: We comprehensively analyzed ACTL6A expression profiles across human malignancies, focusing on correlations with tumor grade, stage, metastasis, and patient survival. Genetic alterations were examined, and the epigenetic landscape of ACTL6A was assessed using rigorous methods. The impact of ACTL6A on immune cell infiltration in the tumor microenvironment was evaluated, along with molecular docking studies and machine learning models. Results: Our analysis revealed elevated ACTL6A expression in various tumors, correlating with poor prognostic indicators such as tumor grade, stage, metastasis, and patient survival. Genetic mutations and epigenetic modifications were identified, along with associations with immune cell infiltration and key cellular pathways. Machine learning models demonstrated ACTL6A's potential for cancer detection. Discussion: ACTL6A emerges as a promising diagnostic and therapeutic target in cancer, with implications for prognosis and therapy. Our study provides comprehensive insights into its carcinogenic actions, highlighting its potential as both a prognostic indicator and a target for anti-cancer therapy. This integrative approach enhances our understanding of ACTL6A's role in cancer pathogenesis and treatment.

Effect of quercetin against pilocarpine-induced epilepsy in mice.

Globally, an estimated 50 million people are affected by epilepsy, a persistent, noncommunicable neurological ailment. Quercetin (QR) is a prevalent flavonoid substance extensively dispersed throughout agricultural life. In a pilocarpine (PILO)-induced epilepsy model in mice, this investigation aimed to determine whether QR has an antiepileptic effect and explore its putative mechanism of action. Fifty mice were allocated into seven groups, with six in every group. The first group received physiological saline, the second group was given diazepam (1 mg/kg), and four groups were administered QR at 50, 100, 150, and 200 mg/kg, respectively. The seventh group (the induction group) received normal saline. After 30 min, all groups were injected intraperitoneally with PILO. The impact of QR on motor coordination was assessed using the rotarod test, while measures such as latency to first seizure, generalized tonic-clonic seizures (GTCS), number of convulsions, and mortality were recorded. Serum samples were collected through the retro-orbital route to measure prostaglandin E2 (PGE2) and interleukin 1 beta (IL-1ß) levels. QR showed no significant difference in motor impairment, but increased duration until the initial seizure occurred and declined the mortality rate, duration of GTCS, and incidence of convulsions. All doses of QR significantly reduced PGE2 levels (P ≤ 0.05). However, QR's effect on IL-1ß reduction was statistically insignificant (P > 0.05). QR's capacity to inhibit PILO-induced epilepsy by decreasing IL-1 and PGE2 levels is supported by this study. The results of this work indicate that QR could have a function to treat acute epilepsy.

Oncogenic Potential of Replication Factor C Subunit 4: Correlations with Tumor Progression and Assessment of Potential Inhibitors.

Replication Factor C Subunit 4 (RFC4), an oncogene implicated in many human cancers, has yet to be extensively studied in many cancer types to determine its expression patterns and tumor tissue function. Various bioinformatics tools were used to analyze RFC4 as a potential oncogene and therapeutic target across many cancers. We first examined RFC4 expression levels in several human tumor types to determine relationships with tumor grade, stage, metastasis, and patient survival. We also examined RFC4's genetic changes, epigenetic methylation, and effect on tumor microenvironment (TME) immune cell infiltration. We also analyzed RFC4's connections with immunological checkpoints to identify potential molecular pathways involved in carcinogenesis. Our findings show that RFC4 is upregulated in several tumor types and associated with poor prognoses in many human cancers. This study shows that RFC4 significantly affects the tumor immunological microenvironment, specifically immune cell populations. Finally, we screened for RFC4-inhibiting pharmacological compounds with anti-cancer potential. This study fully elucidates RFC4's carcinogenic activities, emphasizing its potential as a prognostic biomarker and a target for anti-cancer therapy.

Recent advances in natural nanoclay for diagnosis and therapy of cancer: A review.

Cancer is still one of the deadliest diseases, and diagnosing and treating it effectively remains difficult. As a result, advancements in earlier detection and better therapies are urgently needed. Conventional chemotherapy induces chemoresistance, has non-specific toxicity, and has a meager efficacy. Natural materials like nanosized clay mineral formations of various shapes (platy, tubular, spherical, and fibrous) with tunable physicochemical, morphological, and structural features serve as potential templates for these. As multifunctional biocompatible nanocarriers with numerous applications in cancer research, diagnosis, and therapy, their submicron size, individual morphology, high specific surface area, enhanced adsorption ability, cation exchange capacity, and multilayered organization of 0.7-1 nm thick single sheets have attracted significant interest. Kaolinite, halloysite, montmorillonite, laponite, bentonite, sepiolite, palygorskite, and allophane are the most typical nanoclay minerals explored for cancer. These multilayered minerals can function as nanocarriers to effectively carry a variety of anticancer medications to the tumor site and improve their stability, dispersibility, sustained release, and transport. Proteins and DNA/RNA can be transported using nanoclays with positive and negative surfaces. The platform for phototherapeutic agents can be nanoclays. Clays with bio-functionality have been developed using various surface engineering techniques, which could help treat cancer. The promise of nanoclays as distinctive crystalline materials with applications in cancer research, diagnostics, and therapy are examined in this review.

Nanoarchitecture-based photothermal ablation of cancer: A systematic review.

Photothermal therapy (PTT) is an emerging non-invasive method used in cancer treatment. In PTT, near-infrared laser light is absorbed by a chromophore and converted into heat within the tumor tissue. PTT for cancer usually combines a variety of interactive plasmonic nanomaterials with laser irradiation. PTT enjoys PT agents with high conversion efficiency to convert light into heat to destroy malignant tissue. In this review, published studies concerned with the use of nanoparticles (NPs) in PTT were collected by a systematic and comprehensive search of PubMed, Cochrane, Embase, and Scopus databases. Gold, silver and iron NPs were the most frequent choice in PTT. The use of surface modified NPs allowed selective delivery and led to a precise controlled increase in the local temperature. The presence of NPs during PTT can increase the reactive generation of oxygen species, damage the DNA and mitochondria, leading to cancer cell death mainly via apoptosis. Many studies recently used core-shell metal NPs, and the effects of the polymer coating or ligands targeted to specific cellular receptors in order to increase PTT efficiency were often reported. The effective parameters (NP type, size, concentration, coated polymers or attached ligands, exposure conditions, cell line or type, and cell death mechanisms) were investigated individually. With the advances in chemical synthesis technology, NPs with different shapes, sizes, and coatings can be prepared with desirable properties, to achieve multimodal cancer treatment with precision and specificity.

A Comprehensive Pan-Cancer Analysis Identifies CEP55 as a Potential Oncogene and Novel Therapeutic Target.

Emerging research findings have shown that a centrosomal protein (CEP55) is a potential oncogene in numerous human malignancies. Nevertheless, no pan-cancer analysis has been conducted to investigate the various aspects and behavior of this oncogene in different human cancerous tissues. Numerous databases were investigated to conduct a detailed analysis of CEP55. Initially, we evaluated the expression of CEP55 in several types of cancers and attempted to find the correlation between that and the stage of the examined malignancies. Then, we conducted a survival analysis to determine the relationship between CEP55 overexpression in malignancies and the patient's survival. Furthermore, we examined the genetic alteration forms and the methylation status of this oncogene. Additionally, the interference of CEP55 expression with immune cell infiltration, the response to various chemotherapeutic agents, and the putative molecular mechanism of CEP55 in tumorigenesis were investigated. The current study found that CEP55 was upregulated in cancerous tissues versus normal controls where this upregulation was correlated with a poor prognosis in multiple forms of human cancers. Additionally, it influenced the level of different immune cell infiltration and several chemokines levels in the tumor microenvironment in addition to the response to several antitumor drugs. Herein, we provide an in-depth understanding of the oncogenic activities of CEP55, identifying it as a possible predictive marker as well as a specific target for developing anticancer therapies.

Prostate cancer and microRNAs: New insights into apoptosis.

Prostate cancer (PCa) is known as one of the most prevalent malignancies globally and is not yet curable owing to its progressive nature. It has been well documented that Genetic and epigenetic alterations maintain mandatory roles in PCa development. Apoptosis, a form of programmed cell death, has been shown to be involved in a number of physiological processes. Apoptosis disruption is considered as one of the main mechanism involved in lots of pathological conditions, especially malignancy. There is ample of evidence in support of the fact that microRNAs (miRNAs) have crucial roles in several cellular biological processes, including apoptosis. Escaping from apoptosis is a common event in malignancy progression. Emerging evidence revealed miRNAs capabilities to act as apoptotic or anti-apoptotic factors by altering the expression levels of tumor inhibitor or oncogene genes. In the present narrative review, we described in detail how apoptosis dysfunction could be involved in PCa processes and additionally, the mechanisms behind miRNAs affect the apoptosis pathways in PCa. Identifying the mechanisms behind the effects of miRNAs and their targets on apoptosis can provide scientists new targets for PCa treatment.

The resistance to methoxy polyethylene glycol-epoetin beta in anemic patients of end-stage renal disease.

Background: Chronic kidney disease (CKD) is a global disease, and the number of people affected is increasing due to driving factors such as diabetes, obesity, and hypertension, as well as increased life expectancy. Many patients with CKD suffer anemia throughout the period of their disease. Aim: This research aimed to investigate the relation between resistance to the methoxy polyethylene glycol-epoetin beta (ME-ß) and angiotensin-converting enzyme (ACE) gene polymorphism. Methods: Seventy Iraqi patients with CKD on hemodialysis treatment for at least six months and receiving a subcutaneous injection of ME-ß were selected to enroll in this current study. In addition to these patients, the control group of 20 healthy subjects. Baseline samples (Three blood samples) were obtained and withdrawn from each participant, then 3 and 6 months following the starting sample. In addition, a unique blood sample was taken from each participant in the control group in the early morning hours following 8 h of fasting and before dialysis (for the patients' group). Results: ACE polymorphism did not demonstrate a significant (p ˃ 0.05) relation with changing the dose of ME-ß. Furthermore, there was a negative relationship between ME-ß dose and hemoglobin (Hb) in CKD patients. Comparing ACE polymorphism between good and hypo-response groups shows no significant effect (p ˃ 0.05) on ME-ß therapy. Moreover, the erythropoietin resistance index (ERI) was significantly (p < 0.001) lower in good responders to ME-ß therapy compared to the hypo-response group. Finally, comparing the ERI of the patient, the good response group to the hypo-response group showed no significant association (p ˃ 0.05) with ACE gene polymorphism in response to ME-ß therapy. Conclusion: No relation was determined between the polymorphism ACE gene and the resistance to the ME-ß administration in CKD Iraqi patients.

Anabasis articulata exerts an anti-arthritic effect on adjuvant-induced arthritis in rats.

Anabasis articulata (AA) is commonly found in the Iraqi desert and is utilized in traditional medicine to cure kidney infections, eczema, fever, and diabetes. The paper aimed to identify the anti-arthritic impact of AA on arthritis models in rats. Complete Freund's Adjuvant (CFA) was used intradermally (ID) for the induction of arthritis. The author classified animals into four groups randomly: The first group took normal saline (control), the second group received AA orally for 14 days before induction and continue 17 days after induction, the third group was induced by CFA and received normal saline orally (model group), and the fourth group took AA orally 17 days after induction. AA administration increased body weight (BW) but decreased arthritis index (AI), histopathological scores, and vascular endothelial growth factor expression in synovial cells. AA has an important antiangiogenesis and anti-arthritic activity in arthritis model rats.

Mentha piperita Oil Exerts an Antiepileptic Effect in Pilocarpine and Pentylenetetrazol-Induced Seizures in Mice.

Introduction: Epilepsy is a progressive, chronic neurological disorder characterized by recurrent seizures. Peppermint (Mentha piperita L.) (MP) is one of the most commonly ingested herbal teas or tisanes with a single component. Aim: We aimed to assess the potential antiepileptic and neuroprotective features of MP essential oil (MPO) in pilocarpine (P) and pentylenetetrazol (PTZ) models of epilepsy. Methods: The study used eight groups of mice to assess the anticonvulsant activity of MPO in both the P and PTZ acute models in mice. P (350 mg/kg, i.p.) was given 30 minutes after MPO (1.6, 3.2, and 6.4 ml/kg, i.p.). As a positive control group, diazepam (1 mg/kg, i.p) was used. PTZ (95 mg/kg, i.p.) was given 30 minutes after MPO (6.4 ml/kg, i.p.). The first convulsion's latency time, the number of convulsions, the latency time to death, and the percentage of deaths were calculated in all groups. Results: MPO significantly (P < 0.05) increases the first convulsion's latency time and the death's latency time. Moreover, the essential oil significantly decreases the number of convulsions and reduces the mortality rate compared to the negative control group. Conclusion: MPO at 3.2 and 6.4 ml/kg doses can reduce the percentage and the number of convulsions and increase the latency time of both the first convulsion and death so that it can be used as a supplement in the treatment of epilepsy.

Mining of Marburg Virus Proteome for Designing an Epitope-Based Vaccine.

Marburg virus (MARV) is one of the most harmful zoonotic viruses with deadly effects on both humans and nonhuman primates. Because of its severe outbreaks with a high rate of fatality, the world health organization put it as a risk group 4 pathogen and focused on the urgent need for the development of effective solutions against that virus. However, up to date, there is no effective vaccine against MARV in the market. In the current study, the complete proteome of MARV (seven proteins) was analyzed for the antigenicity score and the virulence or physiological role of each protein where we nominated envelope glycoprotein (Gp), Transcriptional activator (VP30), and membrane-associated protein (VP24) as the candidates for epitope prediction. Following that, a vaccine construct was designed based on CTL, HTL, and BCL epitopes of the selected protein candidates and to finalize the vaccine construct, several amino acid linkers, ß-defensin adjuvant, and PADRE peptides were incorporated. The generated potential vaccine was assessed computationally for several properties such as antigenicity, allergenicity, stability, and other structural features where the outcomes of these assessments nominated this potential vaccine to be validated for its binding affinity with two molecular targets TLR-8 and TLR-4. The binding score and the stability of the vaccine-receptor complex, which was deeply studied through molecular docking-coupled dynamics simulation, supported the selection of our designed vaccine as a putative solution for MARV that should be validated through future wet-lab experiments. Here, we describe the computational approach for designing and analysis of this potential vaccine.

Berbamine and thymoquinone exert protective effects against immune-mediated liver injury via NF-κB dependent pathway.

Background: Immune-mediated hepatitis is a severe impendence to human health, and no effective treatment is currently available. Therefore, new, safe, low-cost therapies are desperately required. Berbamine (BE), a natural substance obtained primarily from Berberis vulgaris L, is a traditional herbal medicine with several bioactivities, such as antimicrobial and anticancer activities. Thymoquinone (TQ), a phytochemical molecule derived from the Nigella sativa plant's black cumin seeds, has attracted interest owing to itsanti-inflammatory, antioxidant, and anticancer properties. Aim: This current study's aims was to examine the protective impacts of BE and TQ in Concanavalin A (ConA)- induced acute liver injury and the action's underlying mechanism. Methods: sixty mice of both sexes were used and divided into four groups (each group with six mice) as follows: Group I obtained distilled water (negative control group). Group II received distilled water with a single dose of 0.1 ml ConA (20 mg/kg) on day 4 by retro-orbital route (model group). Groups III and IV received BE (30 mg/kg/day) and TQ (25 mg/kg/day), respectively, by oral gavage for four successive days, with a single dose of ConA (20 mg/kg) on day 4, then all animals were sacrificed after 8 h and prepared for liver and blood collection. Results: ConA administration increased the ALT, AST, TNF-α, INFγ, and NF-κB significantly (p < 0.001) in the model group. Both BE and TQ could reduce these parameters significantly (p < 0.001) in groups III and IV, respectively, compared to the model group. Conclusion: Both BE and TQ prominently attenuated ConA immune-mediated liver injury. These findings give a remarkable insight into developing a new therapeutic agent for treating hepatitis and other autoimmune diseases.

Drug delivery based on chitosan, ß-cyclodextrin and sodium carboxymethyl cellulose as well as nanocarriers for advanced leukemia treatment.

Medicine/nanotechnology as a new and applicable technique according to drug delivery systems has gained great consideration for cancer treatment. Polysaccharides including, cellulose, ß-cyclodextrin and sodium carboxymethyl cellulose and chitosan as natural bio-materials, are appropriate candidates for designing and formulations of these nanosystems because of the exceptional advantages such as bio-compatibility, bio-degradability, non-toxicity, and gelling characteristics. An intelligent drug delivery platform based on these hybrids nowadays is developed, which can be used for dual-responsive dual-drug delivery. Nanotechnology accompany with biological molecules has been carefully considered to decrease the drawbacks of conventional cancer treatments. Consequently, this review is intended to state and investigate on the latest development on the combination treatment of platforms based on the hybrids of anticancer drugs/nanoparticles/Polysaccharides in the fields of biomedical therapeutics and cancer therapy owing to the bio-compatibility, great surface area, good chemical and mechanical features, the challenges and future perspectives are reported as well.

Delivery LL37 by chitosan nanoparticles for enhanced antibacterial and antibiofilm efficacy.

In this study, the fabrication of LL37-loaded chitosan nanoparticles (CS/LL37-NPs) was based on an ionotropic gelation method between sodium tripolyphosphate (TPP) and chitosan. Synthesized chitosan nanoparticles (CS-NPs) were approved by Fourier Transform Infrared (FTIR), UV-vis spectroscopy, Dynamic Light Scattering (DLS), Scanning Electron Microscope (SEM), and Transmission Electron Microscopy (TEM). The encapsulation efficiency of LL37 in this delivery system (CS/LL37-NPs) was 86.9%. According to in vitro release profile, the release of LL37 from CS/LL37-NPs was almost complete after 5 days. Additionally, CS/LL37-NPs can cause an increase in the half-life and prolonged LL37 antibacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA). This delivery system demonstrated 68% biofilm formation inhibition compared to the LL37 alone. Also, icaA gene expression in the face of CS/LL37-NPs was significantly decreased. This study showed the important role of delivery systems in enhancing LL37 antibacterial and antibiofilm activity which can be suggested as a promising agent in the inhibition of bacterial growth and the prevention of biofilm formation.