Introduction: Toll-Like Receptor 4 (TLR4) is vital for the innate immune system as it recognizes a wide array of pathogens, such as bacteria, fungi, and viruses. TLR4 activates downstream signaling pathways upon recognizing microbial components, triggering and regulating the immune response. With improvements in genomic technologies, it has become possible to identify Single-Nucleotide Polymorphisms (SNPs) in genes coding for immune receptors, such as TLR4. These genetic differences may affect the way TLR4 reacts to various pathogens and thus the intensity and outcome of immune responses. It is essential to have a comprehensive understanding of SNPs associated with TLR4 to assess individual susceptibility to infection and inform personalized medicine strategies. Methods: Multiple scientific literature review databases were utilized to examine TLR4 SNPs and their roles in pathogen recognition, immune signaling, and disease outcomes. These studies elaborated the role of TLR4 polymorphisms in various forms of infections involving bacteria, fungi, and viruses. Results: Some polymorphisms in the TLR4 gene, including rs4986790 [Asp299Gly] and rs4986791 [Thr399Ile], have been associated with differing immune responses and increased susceptibility to septic shock, candidiasis, tuberculosis, and viral infections. This inhibition of TLR4 signaling by the mutant alleles augments some arms of immune response while inhibiting others, which in turn affects the severity of the infection and the response to treatment. Discussion: This review focuses on the identification and examination of SNPs in TLR4 and their association with infectious diseases caused by pathogens. The review also examines the impact of these SNPs on TLR4 signaling pathways and the immune response. Polymorphisms in the TLR4 gene, including rs4986790 [Asp299Gly] and rs4986791 [Thr399Ile], have been associated with differing immune responses and increased susceptibility to septic shock, candidiasis, tuberculosis, and viral infections. Conclusion: Recognition of TLR4 SNPs would provide information on susceptibility to various infections and immune modulation. Current knowledge of genetic variations will lead to the identification of biomarkers for infectious diseases, and consequently, patient-specific treatment and vaccine generation targeted toward specific genotypes in precision medicine, particularly in immunology.

Introduction: Rehmannia (Dihuang) is a perennial herb plant of Rehmannia Libosch. in the Scrophulariaceae family. Rehmannia is one of the "Four Major Huaiqing Medicines". Its taste tropism is described as Gan (sweet), and it is considered non-toxic. The objective of this research is to investigate the differences in volatile compounds identified in flowers and to explore the mechanisms of Rehmannia piasezkii and wild Rehmannia glutinosa in cancer treatment. Methods: Gas Chromatography-Mass Spectrometry (GC-MS) and network pharmacology were used to analyze the differential volatile oil of the flowers of R. piasezkii and wild R. glutinosa (VOFRP and VOFWRG), and to predict their mechanism of action for cancer treatment through molecular docking techniques. Results: A total of 34 common compounds were identified in VOFRP and VOFWRG, including 6 esters, 7 ketones, 5 alkanes, 5 acids, and 2 alcohols. They had distinct chemical properties, with methyl linoleate and methyl oleate standing out as potential differentiated compounds. The key targets were identified by the network pharmacology and molecular docking studies as JAK1, SRC, PDGFRA, PIK3R1, PIK3CA, PDGFRB, PIK3CB, PIK3CD, EGFR, JAK2, and KDR. They had an anticancer effect by interfering with the prolactin signaling pathway, lipid and atherosclerosis, cancer, and prostate cancer. They also regulated tumor cell proliferation, differentiation, and apoptosis by interfering with other signaling pathways. Discussion: The findings offer research directions and data supporting the advancement of Rehmannia flower volatile oils for cancer therapeutics, particularly in developing R. piasezkii and wild R. glutinosa extracts. However, the network pharmacological and molecular docking results lack biological validation. Future experiments should verify whether Rehmannia can treat cancer through these key targets and pathways, thereby strengthening the reliability of these findings. Conclusion: This study investigates VOFRP and VOFWRG and examines their potential anticancer effects and mechanisms. It provides a scientific foundation for the development and utilization of the flowers of R. piasezkii and wild R. glutinosa (FRP and FWRG).

Abstract: Artificial intelligence (AI) is a rapidly expanding field of innovative technology that has great potential to transform many different scientific and technological fields. AI can be used in veterinary treatment and animal disease management to produce better outcomes for people and animals. AI can help in many disciplines, including genetics, cancer research, epidemiology, disease surveillance, therapy and vaccine development, studies on antimicrobial resistance (AMR), and is presented as an essential tool to address worldwide health issues in many fields. Most investigational AI-driven animal care research focuses on data collection, processing, evaluation, and analysis for animal behaviour detection, disease surveillance, growth estimation, and environmental monitoring. This paper describes and investigates the potential consequences of different elements of AI on animal disease and how AI is developing across many disciplines; the most prominent are deep learning and machine learning. “Machine learning” (ML) can be used to create models capable of predicting the future through algorithms that discover patterns in data. The development of AI technologies has sped up the process of drug discovery by locating possible therapeutic targets and improving candidate medications. This paper discusses these advancements while also analyzing the opportunities that lie ahead for artificial intelligence in the field of animal disease control. We also highlight the potential of AI to preserve the wellness of humans and animals across nations, highlighting the role AI plays in advancing the management of animal illnesses.

Background: Breast cancer, a complex disease characterized by aberrant cellular physiology, poses a significant health threat to women globally. Its prevalence and mortality rates emphasize the need to understand its etiology and risk factors. Recent studies recommend a possible association between heavy metal revelation and the development of breast cancer. Objective: The work aimed to study heavy metal exposure in the hair of breast cancer patients across different stages of the disease according to previous work. Methods: The data from already reported studies was collected, including Google Scholar, PubMed, Web of Science, and many more. Results: Previous research has shown elevated levels of cadmium in hair samples from breast cancer patients compared to controls. Other metals like zinc, lead, Hg, mercury, cobalt, nickel, selenium, tin, antimony, scandium, silver, gold, boron, barium, beryllium, calcium, cerium, cesium, gadolinium, manganese, and arsenic play an important role in spreading of breast cancer to people. Additionally, a comparison of metal concentrations in hair samples revealed significant differences between cancer patients and healthy individuals. Correlations between certain metals within each group were also found, suggesting distinct patterns in metal distribution among breast cancer patients. Conclusion: The elevated level of certain metals in hairs from breast cancer patients needs further investigation into the processes underlying their association with disease development and progression. Cadmium and other metals play an important role in breast cancer development either by oral, skin, or food ingestion. Understanding the part of metals in breast cancer may offer insights into preventive strategies and therapeutic interventions.

Background:: Aging is a progressive deterioration characterized by the gradual buildup of physiological alterations as time passes. The aging phenomenon encompasses various interconnected systems within the body, such as the skin, bones, cartilage, and hair. Objective and Methods: In this study, based on the appropriate properties of squalene, including antioxidant, anti-inflammatory, and skin repair properties, a molecular docking study was designed for the drug squalene and proteins related to the dermis and epidermis pathway and collagen production (including Col3A1, Col1A2, FBN1, Decorin, and HAS2). Results and Discussion:: The docking results indicated that the interaction of squalene with hyaluronan synthetase 2 (HAS2) possessed the highest negative binding free energy value of -10.90 KCal/mol, followed by decorin with a value of -9.99 KCal/mol. Also, the inhibition constant values of squalene- HAS2 and squalene-decorin complexes were equal to 1.61 and 7.51 μM, respectively. It has been stated that decorin (as a small proteoglycan) and HAS2 are involved in controlling the assembly of skin fibrils and the biosynthesis of glucosaminoglycans, respectively. Conclusion:: Considering that proteoglycans and glucosaminoglycans play a role in the skin aging process, squalene may be used as an anti-aging agent to induce these pathways and for different purposes. Squalene may be used as a potential agent alone or in combination with other compounds in tissue engineering scaffolds for cosmetic, anti-aging, wound healing, and tissue repair applications.

Abstract: One of the most prevalent cancers throughout the world is colorectal cancer (CRC). Natriuretic peptides are important hormones that have a crucial role in the physiology of humans and other animals. There are a variety of treatments for colon cancer. However, conventional therapies have many side effects and low efficacy in the treatment of this disease. Atrial Natriuretic Peptide (ANP) is one of the most well-known natriuretic peptides involved in regulating blood pressure and blood volume. Studies have demonstrated that ANP has a therapeutic effect on different cancer types. The anti-tumor effect of ANP is exerted by inhibiting DNA synthesis but not inducing apoptosis. The anti-proliferative role of ANP has been reported in human breast, prostate, colon, pancreatic, lung, and ovarian cancer and in many other tumors. Therefore, we review the recent papers on natriuretic peptides in CRC as a common malignancy in adults to assess the pathways of ANP involved in the progression of CRC and its effects on the prevention or treatment of CRC and other cancer types.

Background:: Hepatocellular carcinoma (HCC) is the most common type of cancer. Although HCC treatment has greatly improved over the past few decades, patient survival rates are still very low. Therefore, it is essential to find new treatments for HCC. Apoptosis has been shown to be the most effective in disrupting cancer growth. Improper functioning of proteins in apoptosis can lead to cancer growth. MicroRNAs (miRNAs) are key regulators in the development and progression of HCC. Objective:: Irregular expression of miRNAs involved in apoptosis signaling can lead to tumorigenesis. Therefore, we investigated the effect of the hsa-miR-4270 inhibitor on cell proliferation and apoptosis. Methods:: HepG2 cells were cultured at 37°C and 95% air. Transfection of HepG2 cells was performed by miR-4270 inhibitor and lipofectamine 2000. Cell proliferation of HepG2 cells was determined with MTT assay and different concentrations of miR-4270 specific inhibitors. DNA laddering assay was performed to evaluate the induction of apoptosis. Finally, the transcription level of genes involved in apoptosis, including BAX, BCL2, Caspase3, and p53, was measured by real-time RT-PCR. Results:: The results of MTT and DNA laddering assays showed that the miR-4270 inhibitor declined cell proliferation and induced apoptosis in HepG2 cells. Also, the results of quantitative real-time RT-PCR indicated an upregulation of transcription of BAX, p53 and Caspase3 genes and a decline in expression of BCL2 gene. Conclusion:: Taken together, we found hsa-miR-4270 inhibitor decreased cell proliferation and induced apoptosis in the HepG2 cell line, which can be used as a new therapeutic strategy for HCC patients.

Background: When analyzing multivariate data, it can be challenging to quantify and pinpoint relationships between a collection of consistent characteristics. Reliable computational prediction of cancer patient's response to treatment based on their clinical and molecular profiles is essential in this era of precision medicine. This is essential in helping doctors choose the least contaminated and most potent restorative therapies that are now available. Better patient monitoring and selection are now possible in clinical trials. Methods: This research proposes a novel robust model to aid in the diagnosis of various cancers induced by biomarker proteins (Protein Kinase B, MAPK, and mammalian Target of Rapamycin). Later, various medications (Perifosine, Wortmannin, and Rapamycin) were proposed to cure cancer. Various studies were carried out to obtain all of the results, which aid in the identification of various types of cancer. The drugs mentioned in this essay help to ward off cancer. Scaling and normalization were carried out using parallel coordinates plots and correlation tests, respectively. The boosted tree method and kNN with multiple distance approaches were also used to generate a solid model. The medical diagnosis system was enhanced by training the boosted tree technique to identify various tumors. A robust model was validated by predicting various values that were displayed against the observed value and agreed with the advised strategy to locate biomarkers to show the value of our method. Results: The results show that the predicted and observed values agree with each other, especially for MAPK pathways. The observed correlation coefficient (r2) is 0.9847 without intercept and 0.9849 with intercept. The precise computational prediction of the reaction of cancer patients to treatment based on the patient's clinical and molecular profiles is vital in the period of exactitude medicine. Conclusion: A robust model was validated by predicting the different values that were plotted with the observed value, which agrees with the results of the proposed technique to uncover biomarkers and shows the effectiveness of our technique.

Introduction: Janus kinase 2 (JAK2) is an intracellular signaling protein. JAK2 p. V617F is a common variant in normal karyotype myeloproliferative neoplasms (MPN). Highresolution melting (HRM) analysis is one of the essential methods for detecting the JAK2 p.V617F variant. In this study, we have investigated the effect of DNA concentration on detecting the JAK2 p.V617F variant using the HRM method. Methods: Genomic DNA was extracted from human blood and diluted ten times in distilled water from 1 to 0.03; afterward, HRM was conducted for each dilution (triplicate). Using SPSS v.20.0 software, the mean Tm of each dilution was calculated and compared. Results: The HRM results revealed the JAK2 wild type and variant to have Tms of 81/64°C and 80/76°C, respectively. At the endpoint of the pre-amplification, the dilutions had different emissions. The statistical analysis revealed no statistically significant differences in Tm between samples with varying DNA concentrations (P value > 0.05). Conclusion: There have been no significant differences obtained in the analysis of JAK2 p.V617F point variant in different DNA dilutions, implying that the HRM analysis has no relation to DNA concentration.

Background: Probiotics exhibit significant activity in the immune system by activating multiple immune mechanisms. Resveratrol is a non-flavonoid polyphenol. It has various pharmacological effects, including anti-oxidative, anti-inflammatory, anti-proliferative, and anti-angiogenesis effects. Objectives: The present study investigates the potential immunomodulatory and antitumor activity of the combination treatment of probiotics and resveratrol in sensitive and cisplatin-resistant breast cancer. Methods: In the in vivo study, tumor-bearing mice received one of the following treatments: 2.5*108 CFU/ml probiotics, 50 mg/kg resveratrol, the combination of probiotics and resveratrol, vehicle, or cisplatin. Balb/C mice were inoculated with sensitive EMT6/P and cisplatin resistance EMT6/CPR cancer cell lines, and in vivo antitumor activity was evaluated. Results: The antiproliferative activity of the probiotics, resveratrol, and their combination treatments was assessed using an MTT assay to evaluate lymphocyte proliferation activity. LDH colorimetric assay was conducted to measure the effectiveness of the treatments on the activity of natural killer cells. Nitro blue tetrazolium assay and neutral red method were used to evaluate macrophage function. Conclusion: The combination treatment showed an enhanced effect in splenic lymphocyte proliferation, macrophage function, phagocytosis, and pinocytosis in both cell lines. A significant reduction in tumor size and weight in EMT6/P and EMT6/CPR-bearing mice occurred. Hence, the combination treatment of probiotics and resveratrol was found to have a valuable activity against sensitive and cisplatin-resistant breast cancer cells and might act as a stimulator of the immune system. Therefore, the combination of probiotics and resveratrol deserves further analysis to be used in cancer prevention and treatment.