Symbiotic Antidiabetic Effect of Lactobacillus casei and the Bioactive Extract of Cleome droserifolia (Forssk.) Del. on Mice with Type 2 Diabetes Induced by Alloxan.

The consumption of probiotics protects pancreatic ß-cells from oxidative damage, delaying the onset of type 2 diabetes mellitus (T2DM) and preventing microvascular and macrovascular complications. This study aimed to evaluate the antidiabetic activity of CDE fermented by Lactobacillus casei (ATCC 39539) (LC) in alloxan-induced diabetic rats. The oxidative stress identified by catalase (CAT), serum AST, ALT, ALP, creatinine, urea, and uric acid were measured. The chemical profiles of the plant extract and the fermented extract were studied using HPLC/MS. The potential of the compounds towards the binding pockets of aldose reductase and PPAR was discovered by molecular docking. A significant reduction in fasting blood glucose in alloxan-treated rats. The CAT showed a significant decrease in diabetic rats. Also, serum AST, ALT, ALP, creatinine, urea, and uric acid were significantly decreased in the mixture group. Mild histological changes of pancreatic and kidney tissues suggested that the mixture of probiotics and cleome possesses a marked anti-diabetic effect. Overall, the study suggests that the combination of Cleome droserifolia fermented by Lactobacillus casei exhibits significant antidiabetic activity (p-value=0.05), reduces oxidative stress, improves lipid profiles, and shows potential for the treatment of diabetes.

The role of miRNAs in multiple sclerosis pathogenesis, diagnosis, and therapeutic resistance.

In recent years, microRNAs (miRNAs) have gained increased attention from researchers around the globe. Although it is twenty nucleotides long, it can modulate several gene targets simultaneously. Their mal expression is a signature of various pathologies, and they provide the foundation to elucidate the molecular mechanisms of each pathology. Among the debilitating central nervous system (CNS) disorders with a growing prevalence globally is the multiple sclerosis (MS). Moreover, the diagnosis of MS is challenging due to the lack of disease-specific biomarkers, and the diagnosis mainly depends on ruling out other disabilities. MS could adversely affect patients' lives through its progression, and only symptomatic treatments are available as therapeutic options, but an exact cure is yet unavailable. Consequently, this review hopes to further the study of the biological features of miRNAs in MS and explore their potential as a therapeutic target.

The interplay between toxoplasmosis and host miRNAs: Mechanisms and consequences.

Toxoplasmosis is one of the highly prevalent zoonotic diseases worldwide caused by the parasite Toxoplasma gondii (T. gondii). The infection with T. gondii could pass unidentified in immunocompetent individuals; however, latent cysts remain dormant in their digestive tract, but they could be shed and excreted with feces infesting the environment. However, active toxoplasmosis can create serious consequences, particularly in newborns and infected persons with compromised immunity. These complications include ocular toxoplasmosis, in which most cases cannot be treated. Additionally, it caused many stillbirths and miscarriages. Circulating miRNAs are important regulatory molecules ensuring that the normal physiological role of various organs is harmonious. Upon infection with T. gondii, the tightly regulated miRNA profile is disrupted to favor the parasite's survival and further participate in the disease pathogenesis. Interestingly, this dysregulated profile could be useful in acute and chronic disease discrimination and in providing insights into the pathomechanisms of the disease. Thus, this review sheds light on the various roles of miRNAs in signaling pathways regulation involved in the pathogenesis of T. gondii and provides insights into the application of miRNAs clinically for its diagnosis and prognosis.

Rumex vesicarius L. boosts the effectiveness of sorafenib in triple-negative breast cancer by downregulating BCl2, mTOR, and JNK, and upregulating p21 expression.

BACKGROUND/AIM: Triple-negative breast cancer (TNBC) is characterized by poor prognosis, rapid progression, serious clinical behavior, an elevated risk of metastasis, and resistance to standard treatments. Traditional medicine practitioners value Rumex vesicarius L. (RMV) for a variety of reasons, including the plant's antioxidant capabilities. Our study's goals were to ascertain the efficacy of RMV alone and in combination with sorafenib (SOR) against the aggressive TNBC cell line (MDA-MB-231) and use in vitro and in silico analysis to deduce the fundamental mechanism of action. METHODS: In the current study, molecular operating environment (MOE, 2019.0102) software was used for performing molecular docking. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to determine the cytotoxicity of RMV, SOR or RMV/SOR combination against the TNBC cell line MDA-MB-231 cells. The effects of RMV, SOR, and RMV and SOR combining on mRNAs expressions of the target genes including mTOR, p21, JNK, and BCl2 were evaluated. In TNBC cells, the relative expressions of mRNAs of the genes were examined by using real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: In our experiments, we discovered that both RMV extracts alone and in combination with SOR considerably reduced cancer cell proliferation (IC50 = 0.83 and 0.19 µM, respectively). Additionally, the expression of the tumor suppressor gene p21 was elevated whereas the expression of the invasion and anti-apoptosis genes BCl2, mTOR, and JNK were significantly decreased after treatment with RMV and SOR. Based on in silico analysis, it was found that RMV extract contains bioactive chemicals with a high affinity for inhibiting JNK and VEGFR-2. CONCLUSION: In conclusion, in vitro and in silico investigations show that the RMV extract improves the anticancer efficiency of SOR through molecular processes involving the downregulation of mTOR, BCl2, and JNK1 and overexpression of p21 tumor suppressor gene. Finally, we suggest conducting additional in vivo investigations on RMV and its bioactive components to verify their potential in cancer therapy.

Synergistic antiviral activity of Lactobacillus acidophilus and Glycyrrhiza glabra against Herpes Simplex-1 Virus (HSV-1) and Vesicular Stomatitis Virus (VSV): experimental and In Silico insights.

BACKGROUND: The emergence of different viral infections calls for the development of new, effective, and safe antiviral drugs. Glycyrrhiza glabra is a well-known herbal remedy possessing antiviral properties. OBJECTIVE: The objective of our research was to evaluate the effectiveness of a newly developed combination of the probiotics Lactobacillus acidophilus and G. glabra root extract against two viral models, namely the DNA virus Herpes simplex virus-1 (HSV-1) and the RNA virus Vesicular Stomatitis Virus (VSV), with regards to their antiviral properties. METHODOLOGY: To examine the antiviral impacts of various treatments, we employed the MTT assay and real-time PCR methodology. RESULTS: The findings of our study indicate that the co-administration of L. acidophilus and G. glabra resulted in a significant improvement in the survival rate of Vero cells, while also leading to a reduction in the titers of Herpes Simplex Virus Type 1 (HSV-1) and Vesicular Stomatitis Virus (VSV) in comparison to cells that were not treated. Additionally, an investigation was conducted on glycyrrhizin, the primary constituent of G. glabra extract, utilizing molecular docking techniques. The results indicated that glycyrrhizin exhibited a greater binding energy score for HSV-1 polymerase (- 22.45 kcal/mol) and VSV nucleocapsid (- 19.77 kcal/mol) in comparison to the cocrystallized ligand (- 13.31 and - 11.44 kcal/mol, respectively). CONCLUSIONS: The combination of L. acidophilus and G. glabra extract can be used to develop a new, natural antiviral agent that is safe and effective.

miRNAs role in cervical cancer pathogenesis and targeted therapy: Signaling pathways interplay.

Cervical cancer (CC) is the primary cause of cancer deaths in underdeveloped countries. The persistence of infection with high-risk human papillomavirus (HPV) is a significant contributor to the development of CC. However, few women with morphologic HPV infection develop invasive illnesses, suggesting other mechanisms contribute to cervical carcinogenesis. MicroRNAs (miRNAs, miRs) are small chain nucleic acids that can regulate wide networks of cellular events. They can inhibit or degrade their target protein-encoding genes. They had the power to regulate CC's invasion, pathophysiology, angiogenesis, apoptosis, proliferation, and cell cycle phases. Further research is required, even though novel methods have been developed for employing miRNAs in the diagnosis, and treatment of CC. We'll go through some of the new findings about miRNAs and their function in CC below. The function of miRNAs in the development of CC and its treatment is one of these. Clinical uses of miRNAs in the analysis, prediction, and management of CC are also covered.

In Vivo and In Silico Investigation of the Anti-Obesity Effects of Lactiplantibacillus plantarum Combined with Chia Seeds, Green Tea, and Chitosan in Alleviating Hyperlipidemia and Inflammation.

The increasing prevalence of obesity has become a demanding issue in both high-income and low-income countries. Treating obesity is challenging as the treatment options have many limitations. Recently, diet modification has been commonly applied to control or prevent obesity and its risks. In this study, we investigated novel therapeutic approaches using a combination of a potential probiotic source with prebiotics. Forty-eight adult male Sprague-Dawley rats were selected and divided into seven groups (eight rats per group). The first group was fed a high-fat diet, while the second group was a negative control. The other five groups were orally administered with a probiotic, Lactiplantibacillus plantarum (L. plantarum), and potential prebiotics sources (chia seeds, green tea, and chitosan) either individually or in combination for 45 days. We collected blood samples to analyze the biochemical parameters and dissected organs, including the liver, kidney, and pancreas, to evaluate obesity-related injuries. We observed a more significant decrease in the total body weight by combining these approaches than with individual agents. Moreover, treating the obese rats with this combination decreased serum catalase, superoxide dismutase, and liver malondialdehyde levels. A histopathological examination revealed a reduction in obesity-related injuries in the liver, kidney, and pancreas. Further docking studies indicated the potential role of chia seeds and green tea components in modulating obesity and its related problems. Therefore, we suggest that the daily administration of a pre- and probiotic combination may reduce obesity and its related problems.

Synergistic Antimicrobial Effect of Lactiplantibacillus plantarum and Lawsonia inermis Against Staphylococcus aureus.

PURPOSE: The developed resistance of pathogenic microorganisms towards the currently used antimicrobial agents requires the fast search for newer potent antimicrobials. One of the most important ways to combat the previously mentioned disaster is the use of natural alternatives like medicinal plants. Our study aimed to estimate the anti-inflammatory property, and antibacterial effects of probiotics Lactiplantibacillus plantarum and ethanol extracts of Lawsonia inermis leaves against Staphylococcus aureus when they were used separately or collectively as synergism. MATERIAL AND METHODS: Experimentally induced infected wound model in mice was created and divided into 10 groups then treated for two days by L. plantarum and L. inermis individually or in combination, followed by biochemical assays. The antibacterial, anti-inflammatory, and wound healing activity were evaluated through histopathological sections taken before and after treatment. RESULTS: Our results revealed that L. plantarum and L. inermis mixture could inhibit growth of S. aureus and decrease the minimal inhibitory concentration (MIC) of L. plantarum to 2 mg/mL. The mixture decreased level of both interleukin 6 (IL-6) and interferon-alpha (TNF-α) to a level near the normal uninfected group. Histopathological study showed that animals treated with both L. plantarum and L. inermis had achieved almost 90% healing. CONCLUSION: These results suggest that L. plantarum and L. inermis mixture has synergistic effect on healing of infected wound.

In vitro and computational insights revealing the potential inhibitory effect of Tanshinone IIA against influenza A virus.

Seasonal human influenza is a serious respiratory infection caused by influenza viruses that can be found all over the world. Type A influenza is a contagious viral infection that, if left untreated, can lead to life-threatening consequences. Fortunately, the plant kingdom has many potent medicines with broad-spectrum antiviral activity. Herein, six plant constituents, namely Tanshinone IIA 1, Carnosic acid 2, Rosmarinic acid 3, Glycyrrhetinic acid 4, Baicalein 5, and Salvianolic acid B 6, were screened for their antiviral activities against H1N1 virus using in vitro and in silico approaches. Hence, their anti-influenza activities were tested in vitro to determine inhibitory concentration 50 (IC50) values after measuring their CC50 values using MTT assay on MDCK cells. Interestingly, Tanshinone IIA (TAN) 1 was the most promising member with CC50 = 9.678 µg/ml. Moreover, the plaque reduction assay carried on TAN 1 revealed promising viral inhibition percentages of 97.9%, 95.8%, 94.4%, and 91.7% using concentrations 0.05 µg/µl, 0.025 µg/µl, 0.0125 µg/µl, and 0.006 µg/µl, respectively. Furthermore, in silico molecular docking disclosed the superior affinities of Salvianolic acid B (SAL) 6 towards both surface glycoproteins of influenza A virus (namely, hemagglutinin (HA) and neuraminidase (NA)). The docked complexes of both SAL and TAN inside HA and NA receptor pockets were selected for 100 ns MD simulations followed by MM-GBSA binding free energy calculation to confirm the docking results and give more insights regarding the stability of both compounds inside influenza mentioned receptors, respectively. The selection criteria of the previously mentioned complexes were based on the fact that SAL showed the highest docking scores on both viral HA and NA glycoproteins whereas TAN achieved the best inhibitory activity on the other hand. Finally, we urge more advanced preclinical and clinical research, particularly for TAN, which could be used to treat the human influenza A virus effectively.

Anti-SARS-CoV-2 activities of tanshinone IIA, carnosic acid, rosmarinic acid, salvianolic acid, baicalein, and glycyrrhetinic acid between computational and in vitro insights.

Six compounds namely, tanshinone IIA (1), carnosic acid (2), rosmarinic acid (3), salvianolic acid B (4), baicalein (5), and glycyrrhetinic acid (6) were screened for their anti-SARS-CoV-2 activities against both the spike (S) and main protease (Mpro) receptors using molecular docking studies. Molecular docking recommended the superior affinities of both salvianolic acid B (4) and glycyrrhetinic acid (6) as the common results from the previously published computational articles. On the other hand, their actual anti-SARS-CoV-2 activities were tested in vitro using plaque reduction assay to calculate their IC50 values after measuring their CC50 values using MTT assay on Vero E6 cells. Surprisingly, tanshinone IIA (1) was the most promising member with IC50 equals 4.08 ng µl-1. Also, both carnosic acid (2) and rosmarinic acid (3) showed promising IC50 values of 15.37 and 25.47 ng µl-1, respectively. However, salvianolic acid (4) showed a weak anti-SARS-CoV-2 activity with an IC50 value equals 58.29 ng µl-1. Furthermore, molecular dynamics simulations for 100 ns were performed for the most active compound from the computational point of view (salvianolic acid 4), besides, the most active one biologically (tanshinone IIA 1) on both the S and Mpro complexes of them (four different molecular dynamics processes) to confirm the docking results and give more insights regarding the stability of both compounds inside the SARS-CoV-2 mentioned receptors, respectively. Also, to understand the mechanism of action for the tested compounds towards SARS-CoV-2 inhibition it was necessary to examine the mode of action for the most two promising compounds, tanshinone IIA (1) and carnosic acid (2). Both compounds (1 and 2) showed very promising virucidal activity with a most prominent inhibitory effect on viral adsorption rather than its replication. This recommended the predicted activity of the two compounds against the S protein of SARS-CoV-2 rather than its Mpro protein. Our results could be very promising to rearrange the previously mentioned compounds based on their actual inhibitory activities towards SARS-CoV-2 and to search for the reasons behind the great differences between their in silico and in vitro results against SARS-CoV-2. Finally, we recommend further advanced preclinical and clinical studies especially for tanshinone IIA (1) to be rapidly applied in COVID-19 management either alone or in combination with carnosic acid (2), rosmarinic acid (3), and/or salvianolic acid (4).