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Colorectal cancer (CRC) remains a major global health challenge, with its underlying molecular mechanisms, particularly the role of FOXM1, not yet fully understood. This study employed an integrated approach combining bioinformatics along with experimental validation to explore the role of FOXM1 in CRC. Using advanced computational tools and experimental techniques, we aimed to clarify the biological significance of FOXM1 and its potential impact on CRC progression and treatment. Bioinformatic analyses, including pan-cancer views, mRNA expression analysis, immune infiltrations, pathway enrichment, and functional annotations, highlighted the oncogenic potential of FOXM1 in CRC. Protein and gene expression analyses (western blot and qPCR) were conducted in HCT-116 and HT-29 cells. Platforms like GEPIA and UALCAN confirmed the diagnostic relevance of FOXM1, showing upregulated mRNA expression across various stages and metastasis. The influence of FOXM1 on immune cells, particularly CD4+, CD8+, and B cells, was significant, as revealed by immunohistochemistry. Protein-protein interaction analysis through STRING and CYTOSCAPE identified genes closely linked to FOXM1 in CRC. KEGG pathway enrichment suggested FOXM1's involvement in the p53 pathway, reinforcing its role in oncogenesis. Experimental validation confirmed elevated FOXM1 expression in HCT-116 and HT-29 cells. In summary, this study indicates that targeting FOXM1 could be a promising therapeutic strategy in CRC, emphasizing its importance in the molecular landscape of cancer progression., Competing Interests: Declaration of competing interest The authors state that they do not have any known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aims to compare the characterization of three Lactobacillus strains ( L. helveticus , L. acidophilus , and L. paracasei subsp. paracasei ) in camel milk and bovine milk during fermentation. Our finding showed that the average total viable counts of all three Lactobacilli strains in both milk types reached more than 7.0 log CFU/mL after 16 h of fermentation and continued to increase significantly (p < 0.05) as fermentation increased, which is according to the FAO and WHO, higher than the minimum recommended daily probiotic dose to provide the potential health benefits. The total count of L. paracasei subsp. paracasei was greater in fermented camel and bovine milk (8.76 and 8.98 log CFU/mL, respectively) compared to L. helveticus , and L. acidophilus . The L. helveticus exhibited the highest significant (p < 0.05) acidifying ability for both camel and bovine milk; on the other hand, L. paracasei subsp . paracasei revealed the highest significant (p < 0.05) pH in both milk. The L. acidophilus strain exhibited significantly (p < 0.05) the highest levels of free amino acids groups (FAAGs) among other tested strains in camel milk. It is concluded that the growth, viability, and proteolytic activity of three Lactobacilli strains were found to be mainly dependent on incubation time, strain, and type of milk., Competing Interests: We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We further confirm that any aspect of the work covered in this manuscript that has involved human patients has been conducted with the ethical approval of all relevant bodies. We understand that Dr. Omar Alhaj is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs., (© 2024 The Authors.)

The Siddha system of medicine (SSM) is the oldest medical science practised in the ancient period of the southern part of India and Sri Lanka. Many formulations were described for wound healing in the SSM, with specific diagnostic differentiation in the Siddha literature. Most preparations for wound healing were available in the form of oil-based formulations, especially for external usage. Mathan tailam (MT) and Mahamegarajanga tailam (MMRT) have been used by Siddha physicians and traditional practitioners to treat wounds. Mathan tailam is a popular regimen for skin lacerations, burns, skin infections, diabetic wounds, and dermatitis. Mahamegarajanga tailam has long been used by traditional vaidyars to treat cuts and burns. Both MT and MMRT are clinically well-appreciated drugs for wound healing and need to be studied for their mechanisms of action for scientific documentation. In an in vivo study on albino rats -excisional wound model, the histopathological changes, histo-immune response, biomarker analysis, and mRNA expression were studied and analysed. Wounds treated with MT and MMRT healed faster (p < 0.05) than the untreated group (CNT). Histological investigation showed rapid re-epithelialization, dense collagen deposition, increased enzymatic antioxidant activities and decreased lipid peroxidation in the MT and MMRT groups. mRNA expression reveals MT and MMRT-treated tissues able to induce convergent cell motility in wound space. Our study for the first time provides strong in vivo experimental evidence that Mathan tailam and Mahamegarajanga tailam play a crucial role in promoting skin tissue wound healing through IL-6/VEGF/TNF-α mediated mechanisms. Traditional practices continue to teach us valuable lessons, as seen by their continuous use in their locality for years., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

According to the World Health Organization, infectious diseases, particularly those caused by multidrug-resistant bacteria (MDR), are projected to claim the lives of 15 million people by 2050. Septicemia carries a higher morbidity and mortality rate than infections caused by susceptible Pseudomonas aeruginosa, and MDR-mediated ocular infections can lead to impaired vision and blindness. To identify and develop a potential drug against MDR P. aeruginosa, we employed in silico reverse genetics-based target mining, drug prioritization, and evaluation. Rare Lipoprotein A (RlpA) was selected as the target protein, and its crystal structure was geometrically optimized. Molecular docking and virtual screening analyses revealed that RlpA exhibits strong binding affinity with 11 compounds. Among these, 3-chlorophthalic acid was evaluated, and subsequent in vitro assays demonstrated significant anti-Pseudomonas activity with negligible cytotoxicity. The compound was further evaluated against both drug-susceptible and MDR P. aeruginosa strains in vitro, with cytotoxicity assessed using an MTT assay. The study demonstrated that 3-chlorophthalic acid exhibits potent anti-Pseudomonas activity with minimal toxicity to host cells. Consequently, this compound emerges as a promising candidate against MDR P. aeruginosa, warranting further investigation., 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 Elsevier B.V. All rights reserved.)

Cancer is a life-threatening malignancy and one of the leading global causes of human mortality. New approaches are required for cancer therapy due to the unique properties of cancer cells and the side effects of chemotherapy. Probiotics have gained significant attention in the prevention and treatment of various diseases, including cancer. Therefore, the current study aimed to investigate the anti-cancer effects of probiotics, such as marine Lactobacillus species and their proteins. Five marine Lactobacillus species were isolated and identified from the Tamil Nadu Mangrove Pichavaram (TLMP) forest and named TLMP1, TLMP2, TLMP3, TLMP4, and TLMP5. The Lactobacillus isolates, and their proteins were administered to male golden Syrian hamsters. Tumor formation was effectively controlled in hamsters treated with crude Lactobacillus, extending their lifespan. Additionally, Lactobacillus proteins demonstrated an inhibitory effect on tumor formation in the treated group compared to the control. Molecular docking analysis revealed that Lactobacillus proteins interacted significantly with the cAMP-dependent protein kinase catalytic subunit alpha. Amino acid residues LYS791, MET793, ARG841, ARG842, and LEU844 were involved in active site binding and played a crucial role in inhibiting cAMP-dependent protein kinase., 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 © 2023. Published by Elsevier B.V.)

In the modern era, chronic kidney failure due to diabetes has spread across the globe. Prunetin (PRU), a component of herbal medicines, has a broad variety of pharmacological activities; these may help to slow the onset of diabetic kidney disease. The anti-nephropathic effects of PRU have not yet been reported. The present study explored the potential nephroprotective actions of PRU in diabetic rats. For 28 days, nephropathic rats were given oral doses of PRU (20, 40, and 80 mg/kg). Body weight, blood urea, creatinine, total protein, lipid profile, liver marker enzymes, carbohydrate metabolic enzymes, C-reactive protein, antioxidants, lipid peroxidative indicators, and the expression of insulin receptor substrate 1 (IRS-1) and glucose transporter 2 (GLUT-2) mRNA genes were all examined. Histological examinations of the kidneys, liver, and pancreas were also performed. The oral treatment of PRU drastically lowered the blood glucose, HbA1c, blood urea, creatinine, serum glutamic-oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, lipid profile, and hexokinase. Meanwhile, the levels of fructose 1,6-bisphosphatase, glucose-6-phosphatase, and phosphoenol pyruvate carboxykinase were all elevated, but glucose-6-phosphate dehydrogenase dropped significantly. Inflammatory marker antioxidants and lipid peroxidative markers were also less persistent due to this administration. PRU upregulated the IRS-1 and GLUT-2 gene expression in the nephropathic group. The possible renoprotective properties of PRU were validated by histopathology of the liver, kidney, and pancreatic tissues. It is therefore proposed that PRU (80 mg/kg) has considerable renoprotective benefits in diabetic nephropathy in rats.

Herbicides have been linked to a higher risk of developing diabetes. Certain herbicides also operate as environmental toxins. Glyphosate is a popular and extremely effective herbicide for weed control in grain crops that inhibits the shikimate pathway. It has been shown to negatively influence endocrine function. Few studies have demonstrated that glyphosate exposure results in hyperglycemic and insulin resistance; but the molecular mechanism underlying the diabetogenic potential of glyphosate on skeletal muscle, a primary organ that includes insulin-mediated glucose disposal, is unknown. In this study, we aimed to evaluate the impact of glyphosate on the detrimental changes in the insulin metabolic signaling in the gastrocnemius muscle. In vivo results showed that glyphosate exposure caused hyperglycemia, dyslipidemia, increased glycosylated hemoglobin (HbA1c), liver function, kidney function profile, and oxidative stress markers in a dose-dependent fashion. Conversely, hemoglobin and antioxidant enzymes were significantly reduced in glyphosate-induced animals indicating its toxicity is linked to induce insulin resistance. The histopathology of the gastrocnemius muscle and RT-PCR analysis of insulin signaling molecules revealed glyphosate-induced alteration in the expression of IR, IRS-1, PI3K, Akt, β-arrestin-2, and GLUT4 mRNA. Lastly, molecular docking and dynamics simulations confirmed that glyphosate showed a high binding affinity with target molecules such as Akt, IRS-1, c-Src, β-arrestin-2, PI3K, and GLUT4. The current work provides experimental proof that glyphosate exposure has a deleterious effect on the IRS-1/PI3K/Akt signaling pathways, which in turn causes the skeletal muscle to become insulin resistant and eventually develop type 2 diabetes mellitus., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Glyphosate, an endocrine disruptor, has an adverse impact on human health through food and also has the potential to produce reactive oxygen species (ROS), which can lead to metabolic diseases. Glyphosate consumption from food has been shown to have a substantial part in insulin resistance, making it a severe concern to those with type 2 diabetes (T2DM). However, minimal evidence exists on how glyphosate impacts insulin-mediated glucose oxidation in the liver. Hence the current study was performed to explore the potential of glyphosate toxicity on insulin signaling in the liver of experimental animals. For 16 weeks, male albino Wistar rats were given 50 mg, 100 mg and 250 mg/kg b. wt. of glyphosate orally. In the current study, glyphosate exposure group was linked to a rise in fasting sugar and insulin as well as a drop in serum testosterone. At the same time, in a dose dependent fashion, glyphosate exposure showed alternations in glucose metabolic enzymes. Glyphosate exposure resulted in a raise in H 2 O 2 formation, LPO and a reduction in antioxidant levels those results in impact on membrane integrity and insulin receptor efficacy in the liver. It also registered a reduced levels of mRNA and protein expression of insulin receptor (IR), glucose transporter-2 (GLUT2) with concomitant increase in the production of proinflammatory factors such as JNK, IKKβ, NFkB, IL-6, IL-1β, and TNF-α as well as transcriptional factors like SREBP1c and PPAR-γ leading to pro-inflammation and cirrhosis in the liver which results in the development of insulin resistance and type 2 diabetes. Our present findings for the first time providing an evidence that exposure of glyphosate develops insulin resistance and type 2 diabetes by aggravating NFkB signaling pathway in liver.

Context: Camel milk is used in traditional medicine to treat diabetes mellitus hypertension and other metabolic disorders., Objective: This study evaluated the antisteatotic and antihypertensive effects of camel milk protein hydrolysate (CMH) in high fructose (HF)-fed rats and compared it with the effects afforded by the intact camel milk protein extract (ICM)., Materials and Methods: Adult male Wistar rats were divided into 6 groups ( n  = 8 each) as 1) control, 2) ICM (1000 mg/kg), 3) CMH (1000 mg/kg), 4) HF (15% in drinking water), 5) HF (15%) + ICM (1000 mg/kg), and 6) HF (15%) + CMH (1000 mg/kg). All treatments were given orally for 21 weeks, daily., Results: Both ICM and CMH reduced fasting glucose and insulin levels, serum and hepatic levels of cholesterol and triglycerides, and serum levels of ALT and AST, angiotensin II, ACE, endothelin-1, and uric acid in HF-fed rats. In addition, both ICM and CMH reduced hepatic fat deposition in the hepatocytes and reduced hepatocyte damage. This was associated with an increase in the hepatic activity of AMPK, higher PPARα mRNA, reduced expression of fructokinase C, SREBP1, SREBP2, fatty acid synthase, and HMG-CoA-reductase. Both treatments lowered systolic and diastolic blood pressure. However, the effects of CMH on all these parameters were greater as compared to ICM., Discussion and Conclusions: The findings of this study encourage the use of CMH in a large-scale population and clinical studies to treat metabolic steatosis and hypertension.

The increase in β-lactam-resistant Gram-negative bacteria is a severe recurrent problem in the food industry for both producers and consumers. The development of nanotechnology and nanomaterial applications has transformed many features in food science. The antibacterial activity of zinc oxide nanoparticles (ZnO NPs) and their mechanism of action on β-lactam-resistant Gram-negative food pathogens, such as Escherichia coli , Pseudomonas aeruginosa , Salmonella typhi , Serratia marcescens , Klebsiella pneumoniae , and Proteus mirabilis , are investigated in the present paper. The study results demonstrate that ZnO NPs possesses broad-spectrum action against these β-lactamase-producing strains. The minimal inhibitory and minimal bactericidal concentrations vary from 0.04 to 0.08 and 0.12 to 0.24 mg/mL, respectively. The ZnO NPs elevate the level of reactive oxygen species (ROS) and malondialdehyde in the bacterial cells as membrane lipid peroxidation. It has been confirmed from the transmission electron microscopy image of the treated bacterial cells that ZnO NPs diminish the permeable membrane, denature the intracellular proteins, cause DNA damage, and cause membrane leakage. Based on these findings, the action of ZnO NPs has been attributed to the fact that broad-spectrum antibacterial action against β-lactam-resistant Gram-negative food pathogens is mediated by Zn 2+ ion-induced oxidative stress, actions via lipid peroxidation and membrane damage, subsequently resulting in depletion, leading to β-lactamase enzyme inhibition, intracellular protein inactivation, DNA damage, and eventually cell death. Based on the findings of the present study, ZnO NPs can be recommended as potent broad-spectrum antibacterial agents against β-lactam-resistant Gram-negative pathogenic strains.

This research was carried out to study the variation in ethanol stability and chemical composition of five camel milk samples, including two pasteurized samples (Alwatania and Darir alabaker) and three raw samples (Majaheim, Wadah, and Hamra). Ethanol stability was analyzed by dispersing camel milk samples with 0 to 100% ethanol (v/v). The findings indicate that camel milk samples precipitated after adding an equal volume of ethanol at concentrations between 50% and 64% ethanol, depending on the milk sample. The addition of sodium chloride at different concentrations (1−10%) to camel milk resulted in a significant increase in ethanol stability, and samples from Majaheim and Alwatania exhibited the highest ethanol stability values (88%). In contrast, the addition of EDTA to camel milk for pH ranging between 5.9 and 7.1 has increased ethanol stability with a sigmoidal shape in camel milk. The largest ethanol stability differences were observed in a camel milk sample from Alwatania. Thus, the level of Ca2+ in camel milk may contribute to ethanol stability by shifting the entire profile to higher ethanol stability values. The chemical composition of different camel samples was also determined. The lactose content of camel milk varied significantly (p < 0.05) across samples, ranging from 4.37% in Majaheim camel milk to 4.87% in Alwatania camel milk. The total solids of camel milk varied significantly between raw and pasteurized samples, ranging between 10.17% and 12.10%. Furthermore, protein concentration in camel milk obtained from different camel samples varied, from 2.43% to 3.23% for Hamra and Alwatania, respectively. In conclusion, ethanol stability in camel milk was dependent on the camel breed, pH level, ionic strength, and EDTA addition.

Purpose: Platelet-rich fibrin (PRF) such as leucocyte-rich PRF (L-PRF) and injectable form of PRF (i-PRF) are widely used in various surgical applications. L-PRF- and i-PRF-derived cytokine variations and functional pathways are still unexplored. The aim of the study was to evaluate the expression pattern of Th1-, Th2-, and Th17-related cytokines by L-PRF and i-PRF under in vitro., Methods: Cytokine levels were evaluated using multi-analyte ELISArray kit. Using elevated level of cytokines, the protein-protein interaction and pathway were predicted by computational method., Results: The expressed cytokine levels were higher in L-PRF than in i-PRF. Specifically in L-PRF, IL8, IL2, IL6, and IL1A were expressed abundantly, whereas IL4, IL10, and IL6 were significantly high in i-PRF. Furthermore, protein-protein interaction (PPI) networks (cytokine-cytokine interactions) and pathway analyses were predicted using higher-order cytokines. PPI networks and gene ontology enrichment analysis showed functional variations between L-PRF and i-PRF. Kyoto Encyclopedia of Gene and Genome pathway analysis found that L-PRF mediates NF-k B signaling, Toll-like receptor signaling (TLR), and MAPK signaling via T-cell receptor signaling pathway. i-PRF is significantly involved in JAK-STAT signaling pathway through upregulation of STAT1., Conclusion: Our study concludes that L-PRF and i-PRF act via different pathways that confirm functional variations between them. Therefore, we speculate that L-PRF may be effective in acute phase of chronic wounds such as in diabetes mellitus and immunocompromised patients whereas i-PRF may have a better outcome in acute wounds.

Background: Platelet-rich fibrin (PRF) architecture and ultrastructure plays a crucial role in regulating and coordinating the cellular functions and provides a physical architecture, mechanical stability, and biochemical cues necessary for tissue morphogenesis and homeostasis. No study consciously reported the variation in architecture, ultrastructure, and morphology of leukocyte-rich PRF (L-PRF) and injectable PRF (i-PRF)., Objective: Hence, the present study was aimed to evaluate the fibrin architecture, ultrastructure, and cell contents of autologous L-PRF and i-PRF., Materials and Methods: The autologous L-PRF and i-PRF were prepared from blood samples of healthy donors. The morphological and structural variations were assessed by histopathology, atomic force microscopy, confocal laser scanning microscope, and field emission scanning electron microscope., Results: Disparity was found on architecture and ultrastructure of L-PRF and i-PRF fibrin network. The variation in platelet and leukocyte concentration attributed to the fibrin conformational changes. L-PRF shows thick fibrins with rough surface, whereas in i-PRF, smooth thin fibrins., Conclusions: The current study revealed that there is heterogeneity between L-PRF and i-PRF fibrin matrix architecture, ultrastructure, platelets, leukocytes, and the fibrin content. These speculate that the diameter, width, roughness, and smoothness of fibrin fibers, pore size, and shapes of L-PRF and i-PRF matrix may initiate and mediate the scaffold functions differently., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Microscopy and Ultrastructure.)

Food-borne drug-resistant bacteria have adverse impacts on both food manufacturers and consumers. Disillusionment with the efficacy of current preservatives and antibiotics for controlling food-borne pathogens, especially drug-resistant bacteria, has led to a search for safer alternatives from natural sources. Spirulina have been recognized as a food supplement, natural colorant, and enriched source of bioactive secondary metabolites. The main objectives of this study were to isolate polyphenolic compounds from Spirulina and analyze their antibacterial potential against drug-resistant food-borne bacterial pathogens. We found that fraction B of methanol extract contained a high quantity of polyphenols exhibiting broad spectrum antimicrobial effects against drug-resistant food-borne bacterial pathogens. Potential secondary metabolites, such as benzophenone, dihydro-methyl-phenylacridine, carbanilic acid, dinitrobenzoate, propanediamine, isoquinoline, piperidin, oxazolidin, and pyrrolidine, were identified by gas chromatography and mass spectrophotometry (GCMS). These metabolites are active against both gram-positive and gram-negative pathogens. Our work suggests that phenolic compounds from Spirulina provide a natural and sustainable source of food preservatives for future use., (© 2020 The Author(s).)