The Effect of Probiotic Supplementation on the Gut-Brain Axis in Psychiatric Patients.

The pathophysiology of several psychiatric diseases may entail disturbances in the hypothalamic-pituitary-adrenal (HPA) axis and metabolic pathways. Variations in how these effects present themselves may be connected to individual variances in clinical symptoms and treatment responses, such as the observation that a significant fraction of participants do not respond to current antipsychotic drugs. A bidirectional signaling pathway between the central nervous system and the gastrointestinal tract is known as the microbiota-gut-brain axis. The large and small intestines contain more than 100 trillion microbial cells, contributing to the intestinal ecosystem's incredible complexity. Interactions between the microbiota and intestinal epithelium can alter brain physiology and affect mood and behavior. There has recently been a focus on how these relationships impact mental health. According to evidence, intestinal microbiota may play a role in neurological and mental illnesses. Intestinal metabolites of microbial origin, such as short-chain fatty acids, tryptophan metabolites, and bacterial components that might stimulate the host's immune system, are mentioned in this review. We aim to shed some on the growing role of gut microbiota in inducing/manipulating several psychiatric disorders, which may pave the way for novel microbiota-based therapies.

Sensitive and selective colorimetric detection of Staphylococcus aureus-SPA gene by engineered gold nanosensor.

Staphylococcal protein A (SPA) is an important virulence factor that enables Staphylococcus aureus to evade host immune responses. The current work aims to detect the S. aureus SPA gene by a colorimetric method based on gold nanoparticles (AuNPs). For this purpose, the chromosomal DNA of S. aureus was extracted. Thereafter, primers and thiolated oligonucleotide probe were designed based on protein A sequence data in the gene bank. PCR analysis was performed, and the PCR product was electrophoresed on 2 % agarose gel. Gold nanosensor (Au-Ns) was synthesized by the reaction between AuNPs and the thiolated oligonucleotide probe. The physicochemical properties of AuNPs and Au-Ns were characterized. The detection of the SPA gene was performed based on color change detected by the naked eye and UV-vis spectrophotometry. Finally, the described method was optimized and validated for standard, clinical, and food samples. The PCR analysis showed a characteristic fragment of the SPA gene with a molecular size of 545 base pairs (bp) and a detection limit of 60 pg/ µL. The physicochemical analyses illustrated Au-Ns' correct preparation with a zeta potential of -13.42 mV and particle size range 6-11 nm. Moreover, Au-Ns showed 100 % specificity with a detection limit (DL) of 6 fg/ µL. The proposed method was well described to be applied in clinical and research laboratories.

Nanocarriers: A Reliable Tool for the Delivery of Anticancer Drugs.

Nanomedicines have gained popularity due to their potential therapeutic applications, especially cancer treatment. Targeted nanoparticles can deliver drugs directly to cancer cells and enable prolonged drug release, reducing off-target toxicity and increasing therapeutic efficacy. However, translating nanomedicines from preclinical to clinical settings has been difficult. Rapid advancements in nanotechnology promise to enhance cancer therapies. Nanomedicine offers advanced targeting and multifunctionality. Nanoparticles (NPs) have several uses nowadays. They have been studied as drug transporters, tumor gene delivery agents, and imaging contrast agents. Nanomaterials based on organic, inorganic, lipid, or glycan substances and synthetic polymers have been used to enhance cancer therapies. This review focuses on polymeric nanoparticle delivery strategies for anticancer nanomedicines.

Carnosic Acid Encapsulated in Albumin Nanoparticles Induces Apoptosis in Breast and Colorectal Cancer Cells.

Carnosic acid (CA) is a natural phenolic compound with several biomedical actions. This work was performed to study the use of CA-loaded polymeric nanoparticles to improve the antitumor activity of breast cancer cells (MCF-7) and colon cancer cells (Caco-2). CA was encapsulated in bovine serum albumin (BSA), chitosan (CH), and cellulose (CL) nanoparticles. The CA-loaded BSA nanoparticles (CA-BSA-NPs) revealed the most promising formula as it showed good loading capacity and the best release rate profile as the drug reached 80% after 10 h. The physicochemical characterization of the CA-BSA-NPs and empty carrier (BSA-NPs) was performed by the particle size distribution analysis, transmission electron microscopy (TEM), and zeta potential. The antitumor activity of the CA-BSA-NPs was evaluated by measuring cell viability, apoptosis rate, and gene expression of GCLC, COX-2, and BCL-2 in MCF-7 and Caco-2. The cytotoxicity assay (MTT) showed elevated antitumor activity of CA-BSA-NPs against MCF-7 and Caco-2 compared to free CA and BSA-NPs. Moreover, apoptosis test data showed an arrest of the Caco-2 cells at G2/M (10.84%) and the MCF-7 cells at G2/M (4.73%) in the CA-BSA-NPs treatment. RT-PCR-based gene expression analysis showed an upregulation of the GCLC gene and downregulation of the BCL-2 and COX-2 genes in cells treated with CA-BSA-NPs compared to untreated cells. In conclusion, CA-BSA-NPs has been introduced as a promising formula for treating breast and colorectal cancer.

Anti-Inflammatory, Anti-Apoptotic, and Antioxidant Roles of Honey, Royal Jelly, and Propolis in Suppressing Nephrotoxicity Induced by Doxorubicin in Male Albino Rats.

Nephrotoxicity is one of the limiting factors for using doxorubicin (DOX). Honey, propolis, and royal jelly were evaluated for their ability to protect against nephrotoxicity caused by DOX. Forty-two adult albino rats were divided into control groups. The DOX group was injected i.p. with a weekly dose of 3 mg/kg of DOX for six weeks. The DOX plus honey treated group was injected with DOX and on the next day, received 500 mg/kg/day of honey orally for 21 days. The DOX plus royal jelly treated group was injected with DOX and on the following day, received 100 mg/kg/day of royal jelly orally for 21 days. The DOX plus propolis treated group received DOX and on the following day, was treated orally with 50 mg/kg/day of propolis for 21 days. The DOX plus combined treatment group received DOX and on the following day, was treated with a mix of honey, royal jelly, and propolis orally for 21 days. Results confirmed that DOX raised creatinine, urea, MDA, and TNF-α while decreasing GPX and SOD. Damages and elevated caspase-3 expression were discovered during renal tissue's histopathological and immunohistochemical studies. Combined treatment with honey, royal jelly, and propolis improved biochemical, histological, and immunohistochemical studies in the renal tissue. qRT-PCR revealed increased expression of poly (ADP-Ribose) polymerase-1 (PARP-1) and a decline of Bcl-2 in the DOX group. However, combined treatment induced a significant decrease in the PARP-1 gene and increased Bcl-2 expression levels. In addition, the combined treatment led to significant improvement in the expression of both PARP-1 and Bcl-2 genes. In conclusion, the combined treatment effectively inhibited nephrotoxicity induced by DOX.

Vorinostat enhances the therapeutic potential of Erlotinib via MAPK in lung cancer cells.

BACKGROUND: Lung cancer is the second most common cancer in both men and women, with an estimated 235,760 new cases and 131,880 deaths in 2021 in the US. Despite the modern therapies being available such as radiotherapy and chemotherapy, death rates are still increasing. Erlotinib (ERL) is one of the treatment options for lung cancer, although the probability for the patients to develop resistance to ERL constrains its reliability. The aim of the present study is to assess the synergetic effect of combining ERL with vorinostat (SAHA) on the progression of lung cancer cells. RESULTS: Adenocarcinoma alveolar basal epithelial cells (A549) were treated with either ERL, SAHA as mono drugs or with the combination of them for 24 h. Cytotoxicity assay and cell cycle analysis along with apoptosis detection were investigated. The expression profile of CDH1, TGF1, and MAPK was also assessed. Results showed an elevation in the apoptosis level in all treatments compared to WISH; the normal human amnion-derived cells. Furthermore, the treatments caused the cell cycle to arrest at G2/M, indicating its cytotoxic activity. CONCLUSION: The combination of SAHA and ERL significantly increased the level of apoptosis in lung cancer cells. Meanwhile, this combination treatment downregulated MAPK compared to the mono drugs and the control cells, suggesting the potential role of MAPK in regulating apoptosis and cell cycle machinery in lung cancer.

Molecular characterization and phylogenetic analysis of Rhynchophorus ferrugineus (Olivier) in Eastern Province, Saudi Arabia.

Red palm weevil (RPW) is the most aggressive date palm parasite in the Middle East, and especially in the Gulf region. Originated in Southeast Asia, this pest has been detected in the entire Arabian Peninsula, North Africa, Italy, Latin America, and other territories. It is important to local from obtrusive species, which help augmenting the pest control strategies. In the present study we collected 21 RPW samples from 21 different locations in the Eastern Province, Saudi Arabia to genetically characterize them using RAPD- and ISSR-based clustering. Unweighted pair group method with arithmetic mean (UPGMA) for RAPD data categorized the 21 accessions into seven distinct groups, with Al-Oyonn and Juaymah each categorized in solitary group, meanwhile, UPGMA for ISSR indicated six different groups, with Battaliyah, Al-Oyoon, and Juaymah each assigned to a separate group. Combining RAPD and ISSR data revealed two accession; Al-Oyoon and Juaymah that might be considered obtrusive species. Based on distance calculations, we proposed that the potential origins of RPW collected from these locations are Iran and the United Arab Emirates. However, this assumption needs further studies for confirmation.

Knockdown of c-MYC Controls the Proliferation of Oral Squamous Cell Carcinoma Cells in vitro via Dynamic Regulation of Key Apoptotic Marker Genes.

Oral squamous cell carcinoma (OSCC) is the most common malignant epithelial cancer occurring in the oral cavity, where it accounts for nearly 90% of all oral cavity neoplasms. The c-MYC transcription factor plays an important role in the control of programmed cell death, normal-to-malignant cellular transformation, and progression of the cell cycle. However, the role of c-MYC in controlling the proliferation of OSCC cells is not well known. In this study, c-MYC gene was silenced in OSCC cells (ORL-136T), and molecular and cellular responses were screened. To identify the pathway through which cell death occurred, cytotoxicity, colony formation, western blotting, caspase-3, and RT-qPCR analyzes were performed. Results indicated that knockdown of c-MYC has resulted in a significant decrease in the cell viability and c-MYC protein synthesis. Furthermore, caspase-3 was shown to be upregulated leading to apoptosis via the intrinsic pathway. In response to c-MYC knockdown, eight cell proliferation-associated genes showed variable expression profiles: c-MYC (-21.2), p21 (-2.5), CCNA1(1.8), BCL2 (-1.4), p53(-3.7), BAX(1.1), and CYCS (19.3). p27 expression was dramatically decreased in c-MYC-silenced cells in comparison with control, and this might indicate that the relative absence of c-MYC triggered intrinsic apoptosis in OSCC cells via p27 and CYCS.

New insights on CRISPR/Cas9-based therapy for breast Cancer.

CRISPR/Cas9 has revolutionized genome-editing techniques in various biological fields including human cancer research. Cancer is a multi-step process that encompasses the accumulation of mutations that result in the hallmark of the malignant state. The goal of cancer research is to identify these mutations and correlate them with the underlying tumorigenic process. Using CRISPR/Cas9 tool, specific mutations responsible for cancer initiation and/or progression could be corrected at least in animal models as a first step towards translational applications. In the present article, we review various novel strategies that employed CRISPR/Cas9 to treat breast cancer in both in vitro and in vivo systems.

Gut microbiota metabolites in autistic children: An epigenetic perspective.

Gut microbiota has become an issue of great importance recently due to its major role in autism spectrum disorder (ASD). Over the past three decades, there has been a sustained research activity focused to explain the actual mechanism by which gut microbiota triggers/develops autism. Several genetic and epigenetic factors are involved in this disorder, with epigenetics being the most active area of research. Although the constant investigation and advancements, epigenetic implications in ASD still need a deeper functional/causal analysis. In this review, we describe the major gut microbiota metabolites and how they induce epigenetic changes in ASD along with interactions through the gut-brain axis.

Temozolomide modulates the expression of miRNAs in colorectal cancer.

Cancer is the second leading cause of death globally, where nearly 1 in 6 deaths is due to cancer, with 70% of all deaths from cancer occur in low- and middle-income countries. The overall lifetime risk of developing colorectal cancer is 1 in 22 in men and 1 in 24 in women. In this work, we aimed to evaluate the role of temozolomide (TMZ) in controlling colon cancer cells (CRC) via regulating the miRnome. For this purpose, CRC cells (CaCo-2) were treated with 50 µM of TMZ for 48 h. Cell count using trypan test and cytotoxicity using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) were carried out, and the obtained results indicated a significant decrease in cell count (p = 0.029), and in the cell viability (p = 0.0019). Cell cycle analysis was performed using flow cytometer, and results showed that TMZ arrested CRC cells at G2/M phase. A total of 84 miRNAs were profiled using real time PCR, and the results indicated that TMZ treatment upregulated 15 of 84 miRNAs panel profiled and downregulated the rest. The TMZ-upregulated/downregulated miRNAs were predicted to interact with many epigenetic-related proteins i.e., DNMTs, EZH2, and SUV31H1. This study shed some light on the role of TMZ in regulating the miRnome of CRC and hence in different types of cancers.

Triple negative breast cancer in the era of miRNA.

The objective of this review is to elucidate the role of miRNAs in triple negative breast cancer (TNBC). To achieve our goal, we searched databases such as PubMed, ScienceDirect, Springer, Web of Science and Scopus. We retrieved up to 1233 articles, based a rigorous selection criterion, only 197 articles were extensively reviewed. We selected articles only addressing TNBC, but not other types of breast cancer, with the employed approach being miRNA analysis and/or profiling. Our extensive review resulted in grouping of miRNAs into categories in which specific members of miRNAs have roles in specific mechanism in TNBC i.e., carcinogenesis, invasion, metastasis, apoptosis, diagnosis, prognosis, and treatment. TNBC is an aggressive subtype of breast cancer; therefore, different approaches for accurate diagnosis, prognosis and treatment are needed. In this review we summarize the up-to-date miRNA profiling, prognostic, and therapeutic findings that add to the route of controlling TNBC.

Vorinostat-loaded titanium oxide nanoparticles (anatase) induce G2/M cell cycle arrest in breast cancer cells via PALB2 upregulation.

Breast cancer is a group of diseases in which cells divide out of controlled, typically resulting in a mass. Erlotinib is targeted cancer drug which functions as an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. It is used mainly to treat of non-small cell lung cancer patients and has an action against pancreatic cancer. Vorinostat (aka suberanilohydroxamic acid) is an inhibitor of histone deacetylases (HDAC), which has an epigenetic modulation activity. It is used to treat cutaneous T cell lymphoma. In the present study, the erlotinib (ERL) and vorinostat (SAHA) loaded TiO2 nanoparticles (NPs) were used for the treatment of the breast cancer cells (MDA-MB-231 and MCF-7) and human cancerous amniotic cells (WISH). Cell count and viability were negatively affected in all treatments compared to normal cells and bare TiO2 NPs. Apoptosis results indicated a significant increase in the total apoptosis in all treatments compared with control cells. ERL- and SAHA-loaded TiO2 NPs treatments arrested breast cancer cells at G2/M phase, which indicate the cytotoxic effect of these treatment. Partner and localizer of BRCA2 (PALB2) gene expression was assessed using qPCR. The results indicate that PLAB2 was upregulated in ERL- and SAHA-loaded TiO2 NPs compared with control cells and can be used as nanocarrier for chemotherapy drugs. However, this conclusion necessitates further confirmative investigation.

Coronavirus diseases 2019: Current biological situation and potential therapeutic perspective.

Coronavirus Disease 2019 (COVID-19) caused by a Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was first reported in Wuhan, China at the end of December 2019. SARS-CoV-2 is a highly pathogenic zoonotic virus and closely related to the Severe Acute Respiratory Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The COVID-19 was declared as a global pandemic due to its high infectiousness, and worldwide morbidities and mortalities. The Chinese scientists at the start of the outbreak reported genome sequences, which made the characterization of glycoproteins and other structural proteins possible. Moreover, researchers across the world have widely focused on understanding basic biology, developing vaccines, and therapeutic drugs against the COVID-19. However, until now, no promising treatment options, as well as vaccines, are available. In this review, we have described SARS-CoV-2's genome, transmission, and pathogenicity. We also discussed novel potential therapeutic agents that can help to treat the COVID-19 patients.