Green-synthesized copper oxide nanoparticles induce apoptosis and up-regulate HOTAIR and HOTTIP in pancreatic cancer cells.

Aim: Cu2O nanoparticles were synthesized using an extract from S. latifolium algae (SLCu2O NPs). Their effect on PANC-1 cells and the expression of two drug resistance-related lncRNAs were evaluated in comparison with Arsenic trioxide. Materials & methods: SLCu2O NPs were characterized using XRD, SEM, and TEM microscopies. The effects of SLCu2O NPs on cell cytotoxicity, cell cycle, and apoptosis, and expression of two drug resistance-related lncRNAs were examined using MTT assay, flow cytometry, and real-time PCR, respectively. Results: SLCu2O NPs demonstrated anti-cancer properties against PANC-1 cells comparable to Arsenic trioxide, and the expression of lncRNAs increased upon treatment with them. Conclusion: SLCu2O NPs demonstrate anti-cancer properties against PANC-1 cells; however, using gene silencing strategies along with SLCu2O NPs is suggested.

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Obesity and thyroid cancer: unraveling the connection through a systematic review and meta-analysis of cohort studies.

Background: The relationship between adiposity indicators and thyroid cancer (TC) risk has garnered increasing attention due to the rising prevalence of obesity and its potential impact on cancer incidence. We conducted a comprehensive meta-analysis to investigate this association across various effect measures. Method: Until July 2022, a comprehensive search of databases was conducted to identify cohort studies that assessed the association between adiposity and the development of TC. Meta-analysis was performed using random effects models. Subgroup analyses were conducted to explore heterogeneity. Publication bias was assessed using Begg's tests. Results: A systematic literature search identified 27 eligible studies reporting odds ratios (OR), relative risks (RR), or hazard ratios (HR) as effect measures. Pooling the studies irrespective of the effect measure, a significant positive association between adiposity indicators and TC risk was observed, yielding an effect estimate of 1.16 (95% CI 1.12-1.21). The combined effect estimate for OR/RR studies was 1.10 (95%CI 1.04-1.17), while HR studies yielded an effect estimate of 1.20 (95%CI 1.13-1.26). Subgroup analyses revealed associations across different age groups, obesity indices, and regions, with some variations based on effect measure. Meta-regression identified follow-up duration as a confounding factor only in HR studies. Conclusion: The synthesis of 27 studies with diverse designs and populations underscores a robust positive association between adiposity and TC risk, providing compelling evidence for the potential role of increased adiposity in TC development. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01425-3.

Harnessing the Power of CAR-NK Cells: A Promising Off-the-Shelf Therapeutic Strategy for CD38-Positive Malignancies.

Background: CD38 is highly expressed on multiple myeloma (MM) cells and has been successfully targeted by different target therapy methods. This molecule is a critical prognostic marker in both diffuse large B-cell lymphoma and chronic lymphocytic leukemia. Objective: We have designed and generated an anti-CD38 CAR-NK cell applying NK 92 cell line. The approach has potential application as an off-the-shelf strategy for treatment of CD38 positive malignancies. Methods: A second generation of anti-CD38 CAR-NK cell was designed and generated, and their efficacy against CD38-positive cell lines was assessed in vitro. The PE-Annexin V and 7-AAD methods were used to determine the percentage of apoptotic target cells. Flow cytometry was used to measure IFN-γ, Perforin, and Granzyme-B production following intracellular staining. Using in silico analyses, the binding capacity and interaction interface were evaluated. Results: Using Lentivirus, cells were transduced with anti-CD38 construct and were expanded. The expression of anti-CD38 CAR on the surface of NK 92 cells was approximately 25%. As we expected from in silico analysis, our designed CD38-chimeric antigen receptor was bound appropriately to the CD38 protein. NK 92 cells that transduced with the CD38 chimeric antigen receptor, generated significantly more IFN-γ, perforin, and granzyme than Mock cells, and successfully lysed Daudi and Jurkat malignant cells in a CD38-dependent manner. Conclusion: The in vitro findings indicated that the anti-CD38 CAR-NK cells have the potential to be used as an off-the-shelf therapeutic strategy against CD38-positive malignancies. It is recommended that the present engineered NK cells undergo additional preclinical investigations before they can be considered for subsequent clinical trial studies.

Does one-anastomosis gastric bypass provide better outcomes than sleeve gastrectomy in patients with BMI greater than 50? A systematic review and meta-analysis.

In patients with BMI greater than 50, sleeve gastrectomy (SG) may not be adequate to treat obesity. To determine whether one-anastomosis gastric bypass (OAGB) can provide better outcomes compared with SG in patients with BMI greater than 50, a systematic review and meta-analysis was conducted, including a total of nine retrospective studies with a total of 2332 participants. There was a significant difference in the percentage of excess weight loss [weighted mean difference (WMD): 8.52; 95% CI: 5.81-11.22; P<0.001) and percentage of total weight loss (WMD: 6.65; 95% CI: 5.05-8.24; P<0.001). No significant differences were seen in operative time (WMD: 1.91; 95% CI: -11.24 to 15.07; P=0.77) and length of stay in hospital (WMD: -0.41; 95% CI: -1.18 to 0.37; P=0.30) between the two groups. There were no significant differences between OAGB with SG in Clavien-Dindo grades I-III [odds ratio (OR): 1.56; 95% CI: 0.80-3.05], or grade IV complications (OR: 0.72; 95% CI: 0.18-2.94). The meta-analysis on remission of type 2 diabetes indicated a comparable effect between SG and OAGB (OR: 0.77; 95% CI: 0.28-2.16). The OAGB group had a significantly higher rate of remission of hypertension compared with the SG group (OR: 1.63; 95% CI: 1.06-2.50). The findings of this meta-analysis suggest that the OAGB accomplished a higher percentage of total weight loss and percentage of excess weight loss at short-term and mid-term follow-up but, there was no major difference between the OAGB and SG operations in terms of perioperative outcomes, complications, and diabetes remission.

Hub genes and pathways in gastric cancer: A comparison between studies that used normal tissues adjacent to the tumour and studies that used healthy tissues as calibrator.

Several bioinformatics studies have been performed on high-throughput expression data to determine the cellular pathways and hub genes affected by Gastric cancer (GC). However, these studies differ in using a healthy tissue or normal tissue adjacent to the tumour (NAT) as calibrator tissues. This study was designed to find how using healthy or NAT tissues as calibrator tissues could affect pathway enrichment data and hub genes in GC. Two gene expression datasets with NAT tissues (GSE79973 and GSE118916) and one dataset with healthy tissues (GSE54129) were downloaded and processed by the limma package to screen the differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analysis were performed by the Enrichr online tool. Protein-protein interaction network construction, module analysis, and hub genes selection were performed by Cytoscape software, Molecular Complex Detection plugin, and cytoHubba plugin, respectively. The gene expression profiling interactive analysis web server was used to analyse RNA sequencing expression data from The Cancer Genome Atlas Program. The Kaplan-Meier plotter was used to perform survival analysis. Our results showed that some KEGG and GO pathways were shared between studies with NAT and the study with healthy tissues. However, some terms, especially inflammation-related terms, were missed when NAT tissues were used as calibrator tissues. Also, only FN1 and COL1A1 are common hub genes between DEGs of the studies with NAT and healthy tissues. Since hub genes are usually extracted and suggested as candidate targets for GC diagnosis, prognosis, or treatment, selecting healthy or NAT tissues may affect the hub genes selection.

Receptor tyrosine kinase inhibitors in cancer.

Targeted therapy is a new cancer treatment approach, involving drugs that particularly target specific proteins in cancer cells, such as receptor tyrosine kinases (RTKs) which are involved in promoting growth and proliferation, Therefore inhibiting these proteins could impede cancer progression. An understanding of RTKs and the relevant signaling cascades, has enabled the development of many targeted drug therapies employing RTK inhibitors (RTKIs) some of which have entered clinical application. Here we discuss RTK structures, activation mechanisms and functions. Moreover, we cover the potential effects of combination drug therapy (including chemotherapy or immunotherapy agents with one RTKI or multiple RTKIs) especially for drug resistant cancers.

Changes in Bone Turnover Markers after Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy: a Systematic Review and Meta-Analysis.

This systematic review and meta-analysis was performed to compare the alterations in bone turnover markers between SG and RYGB. A literature search was conducted in PubMed, Medline, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases to find the studies. There was significant less increment in osteocalcin [WMD = - 5.98, 95% CI (- 9.30, - 2.47) P < 0.01] and parathyroid hormone (PTH) [WMD = - 9.59, 95% CI (- 15.02, - 4.16) P < 0.01] in the SG group compared to the RYGB group. No significant differences were seen in change of C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type I collagen (PINP), Ca, and 25(OH)-D between SG and RYGB groups. According to our meta-analysis, bone formation markers appear to have more increment following RYGB than SG. This observation is accompanied by a larger increase in PTH after RYGB patients compared to SG patients. PROSPERO: CRD42022308985.

The effects of medical linear accelerator X-rays on human peripheral blood lymphocytes in the presence of glucosamine.

Glucosamine is widely prescribed as a dietary supplement used to treat arthritis. In this study, the radioprotective ability of glucosamine was evaluated against radiation-induced genotoxicity and cytotoxicity in human peripheral blood lymphocytes. Blood samples were collected from five healthy male donors and were divided into four groups. Isolated lymphocytes and blood samples were treated with 10 µM of glucosamine for 2 h before exposure to 2 Gy radiation. The radioprotective potential of glucosamine was assessed by micronucleus assay, reactive oxygen species (ROS) level analysis, and flow cytometry. Irradiation significantly increased the micronuclei frequency as compared to the control group. Contrary to that pretreatment with glucosamine before irradiation significantly reduced the frequency of micronuclei. Furthermore, pretreatment with glucosamine significantly prevented the percentage of apoptotic lymphocytes. Also, glucosamine pretreatment significantly reduced the production of ROS in irradiated lymphocytes. This study shows glucosamine to be a potent radioprotector against radiation that induces DNA damage and apoptosis in human lymphocytes. Several additional in vivo and in vitro studies are needed before glucosamine can be considered as a radioprotective candidate in patients undergoing radiation therapy.

The role of endoplasmic reticulum stress in the regulation of long noncoding RNAs in cancer.

Cancer cells must overcome a variety of external and internal stresses to survive and proliferate. These unfavorable conditions include the accumulation of mutations, nutrient deficiency, oxidative stress, and hypoxia. These stresses can cause aggregation of misfolded proteins inside the endoplasmic reticulum. Under these conditions, the cell undergoes endoplasmic reticulum stress (ER-stress), and consequently initiates the unfolded protein response (UPR). Activation of the UPR triggers transcription factors and regulatory factors, including long noncoding RNAs (lncRNAs), which control the gene expression profile to maintain cellular stability and hemostasis. Recent investigations have shown that cancer cells can ensure their survival under adverse conditions by the UPR affecting the expression of lncRNAs. Therefore, understanding the relationship between lncRNA expression and ER stress could open new avenues, and suggest potential therapies to treat various types of cancer.

Crosstalk between lncRNAs in the apoptotic pathway and therapeutic targets in cancer.

The assertion that a significant portion of the mammalian genome has not been translated and that non-coding RNA accounts for over half of polyadenylate RNA have received much attention. In recent years, increasing evidence proposes non-coding RNAs (ncRNAs) as new regulators of various cellular processes, including cancer progression and nerve damage. Apoptosis is a type of programmed cell death critical for homeostasis and tissue development. Cancer cells often have inhibited apoptotic pathways. It has recently been demonstrated that up/down-regulation of various lncRNAs in certain types of tumors shapes cancer cells' response to apoptotic stimuli. This review discusses the most recent studies on lncRNAs and apoptosis in healthy and cancer cells. In addition, the role of lncRNAs as novel targets for cancer therapy is reviewed here. Finally, since it has been shown that lncRNA expression is associated with specific types of cancer, the potential for using lncRNAs as biomarkers is also discussed.

A Comprehensive Review of Biological Roles and Interactions of Cullin-5 Protein.

Ubiquitination is a modification of proteins that has a powerful impact on protein function along with other cellular functions. This reaction is regulated through major enzymes, including E3 ligase as a chief enzyme. The Cullin-5 ubiquitin ligase (Cul5) possesses a variety of substrates that maintain the process of ubiquitination as well as proteasomal degradation. It regulates cell development, proliferation, and other physiological tasks in the human body. Moreover, it has been discovered that the expression of Cul5 plays a significant role in specific cancer cells while affecting the progression of tumor cells. This review is based on current knowledge about Cul5 and its expression, signaling pathways, regulation, virus-related responses, and inhibitors for therapeutic strategies.

The Impact of Polyphenolics in the Management of Breast Cancer: Mechanistic Aspects and Recent Patents.

BACKGROUND: Breast cancer is the most frequently diagnosed type of cancer in women, accounting for 2.1 million cases, and stands as the fifth leading cause of death. Several treatment strategies are available, such as surgical resection, radiation, hormonal therapy, and conventional chemotherapy; however, these are associated with severe adverse effects in the patients. OBJECTIVES: This review aims to summarize the different studies (in vitro, in vivo, and new patents) concerning the therapeutic potential of plant polyphenolics in the management of breast cancer, published in the period from January 2016 to January 2021. Moreover, this review will focus on the underlying mechanisms of action and molecular characteristics of these compounds. METHODS: The data of this review were collected from different scientific databases, such as Pub- Med, Science Direct, Google Scholarship, SciFinder, and Egyptian Knowledge Bank (EKB). RESULTS: During the period 2016-2021, in the in vitro studies, investigation on 52 compounds of polyphenolic nature with promising anti-breast cancer activity has been conducted, while 14 compounds have been reported via in vivo studies. Besides, about 15 compounds have been registered as patent drugs. Different mechanisms of action and molecular targets have been reported, providing a clarified basis and precise reflection of the anticancer properties of these compounds against breast cancer. CONCLUSION: Polyphenolics represent a comprehensive source of anticancer lead compounds against the progression of breast cancer invasion and metastasis.

Probiotics for the Chemoprotective Role against the Toxic Effect of Cancer Chemotherapy.

BACKGROUND: Chemo- and radiation therapy-based clinical management of different types of cancers is associated with toxicity and several side effects. Therefore, there is always an unmet need to explore agents that reduce such risk factors. Among these, natural products have attracted much attention because of their potent antioxidant and antitumor effects. In the past, some breakthrough outcomes established that various bacteria in the human intestinal gut are bearing growth-promoting attributes and suppressing the conversion of pro-carcinogens into carcinogens. Hence probiotics integrated approaches are nowadays being explored as rationalized therapeutics in the clinical management of cancer. METHODS: Here, published literature was explored to review chemoprotective roles of probiotics against toxic and side effects of chemotherapeutics. RESULTS: Apart from excellent anti-cancer abilities, probiotics alleviate toxicity & side effects of chemotherapeutics, with a high degree of safety and efficiency. CONCLUSION: Preclinical and clinical evidence suggests that due to the chemoprotective roles of probiotics against side effects and toxicity of chemotherapeutics, their integration in chemotherapy would be a judicious approach.

Exploring the Potential of Aromatherapy as an Adjuvant Therapy in Cancer and its Complications: A Comprehensive Update.

BACKGROUND: Aromatherapy is a traditional practice of employing essential oils for therapeutic purposes, which is currently headed under the category of complementary and adjuvant medicine. OBJECTIVE: The aim of this review is to summarize the potential health benefits of aromatic essential oil from old times till the present. Moreover, some mechanisms which can be utilized as a basis for aromatherapy in cancer and cancer-linked complications have been proposed. METHODS: To find out the relevant and authentic data, several search engines like Science direct, Pubmed, research gate, etc. were thoroughly checked by inserting keywords like aromatherapy, complementary, and adjuvant therapy in the context of the review. RESULTS: The results depicted the anti-cancer potential of chemical constituents of essential oil against different types of cancer. Moreover, the essential oils showed the promising anti-inflammatory, anti-microbial, antioxidant, and anti-mutagenic properties in several studies, which collectively can form the basis for initiation of its anti-cancer use. CONCLUSION: Aromatherapy can serve as an adjuvant economic therapy in cancer after the standardization of protocol.

Exploring the role of polyphenols in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, inflammatory and autoimmune disorder which is mainly characterized by inflammation in joints, bone erosions and cartilaginous destruction that leads to joint dysfunction, deformation, and/or permanent functional impairment. The prevalence of RA is increasing, incurring a considerable burden on healthcare systems globally. The exact etiology of RA is unknown, with various pathways implicated in its pathophysiology. Non-steroidal anti-inflammatory drugs (NSAIDs) including celecoxib, diclofenac and ibuprofen, disease-modifying anti-rheumatic drugs (DMARD) including azathioprine, methotrexate and cyclosporine, biological agents including anakinra, infliximab, and rituximab and immunosuppressants are used for symptomatic relief in patients with RA, but these medications have severe adverse effects such as gastric ulcers, hypertension, hepatotoxicity and renal abnormalities which restrict their use in the treatment of RA; new RA treatments with minimal side-effects are urgently required. There is accumulating evidence that dietary polyphenols may show therapeutic efficacy in RA through their antioxidant, anti-inflammatory, apoptotic, and immunosuppressant activities and modulation of the tumor necrosis factor-α (TNF-α), interleukin (IL)-6, mitogen-activated protein kinase (MAPK), IL-1ß, c-Jun N-terminal kinase (JNK), and nuclear factor κ light-chain-enhancer of activated B cell (NF-κB) pathways. While resveratrol, genistein, carnosol, epigallocatechin gallate, curcumin, kaempferol, and hydroxytyrosol have also been studied for the treatment of RA, the majority of data are derived from animal models. Here, we review the various pathways involved in the development of RA and the preclinical and clinical data supporting polyphenols as potential therapeutic agents in RA patients. Our review highlights that high-quality clinical studies are required to decisively establish the anti-rheumatic efficacy of polyphenolic compounds.

Flavonoids, the Family of Plant-Derived Antioxidants Making Inroads into Novel Therapeutic Design Against Ionizing Radiation-Induced Oxidative Stress in Parkinson's Disease.

BACKGROUND: Ionizing radiation from telluric sources is unceasingly an unprotected pitfall to humans. Thus, the foremost contributors to human exposure are global and medical radiations. Various evidences assembled during preceding years reveal the pertinent role of ionizing radiation- induced oxidative stress in the progression of neurodegenerative insults, such as Parkinson's disease, which have been contributing to increased proliferation and generation of reactive oxygen species. OBJECTIVE: This review delineates the role of ionizing radiation-induced oxidative stress in Parkinson's disease and proposes novel therapeutic interventions of flavonoid family, offering effective management and slowing down the progression of Parkinson's disease. METHODS: Published papers were searched in MEDLINE, PubMed, etc., published to date for indepth database collection. RESULTS: The oxidative damage may harm the non-targeted cells. It can also modulate the functions of the central nervous system, such as protein misfolding, mitochondria dysfunction, increased levels of oxidized lipids, and dopaminergic cell death, which accelerate the progression of Parkinson's disease at the molecular, cellular, or tissue levels. In Parkinson's disease, reactive oxygen species exacerbate the production of nitric oxides and superoxides by activated microglia, rendering death of dopaminergic neuronal cell through different mechanisms. CONCLUSION: Rising interest has extensively engrossed in the clinical trial designs based on the plant-derived family of antioxidants. They are known to exert multifarious impact on neuroprotection via directly suppressing ionizing radiation-induced oxidative stress and reactive oxygen species production or indirectly increasing the dopamine levels and activating the glial cells.

Current Insight into the Therapeutic Potential of Phytocompounds and their Nanoparticle-Based Systems for Effective Management of Lung Cancer.

Lung cancer is the second most common cancer and the primary cause of cancer-related death in both men and women worldwide. Due to diagnosis at an advanced stage, it is associated with high mortality in the majority of patients. At present, various treatment approaches are available, such as chemotherapy, surgery, and radiotherapy, but all these approaches usually cause serious side effects like degeneration of normal cells, bone marrow depression, alopecia, extensive vomiting, etc. To overcome the aforementioned problems, researchers have focused on the alternative therapeutic approach in which various natural compounds are reported, which possessed anti-lung cancer activity. Phytocompounds exhibit their anti lung cancer activity via targeting various cell-signaling pathways, apoptosis and cell cycle arrest, and by regulating antioxidant status and detoxification. Apart from the excellent anti-cancer activity, clinical administration of phytocompounds is confined because of their high lipophilicity and low bioavailability. Therefore, researchers show their concern in the development of a stable, safe and effective approach of treatment with minimal side effects by the development of nanoparticle-based delivery of these phytocompounds to the target site. Targeted delivery of phytocompound through nanoparticles overcomes the aforementioned problems. In this article, the molecular mechanism of phytocompounds, their emerging combination therapy, and their nanoparticles-based delivery systems in the treatment of lung cancer have been discussed.

Development of neoantigens: from identification in cancer cells to application in cancer vaccines.

INTRODUCTION: The discovery of neoantigens as mutated proteins specifically expressed in tumor cells but not in normal cells has led to improved cancer vaccines. Targeting neoantigens can induce anti-tumor T-cell responses to destroy tumors without damaging healthy cells. Extensive advances in genome sequencing technology and bioinformatics analysis have made it possible to discover and design effective neoantigens for use in therapeutic cancer vaccines. Neoantigens-based therapeutic personalized vaccines have shown promising results in cancer immunotherapy. AREAS COVERED: We discuss the types of cancer neoantigens that can be recognized by the immune system in this review. We also summarize the detection, identification, and design of neoantigens and their appliction in developing cancer vaccines. Finally, clinical trials of neoantigen-based vaccines, their advantages, and their limitations are reviewed. From 2015 to 2020, the authors conducted a literature search of controlled randomized trials and laboratory investigations that that focused on neoantigens, their use in the design of various types of cancer vaccines. EXPERT OPINION: Neoantigens are cancer cell-specific antigens, which their expression leads to the immune stimulation against tumor cells. The identification and delivery of specific neoantigens to antigen-presenting cells (APCs) with the help of anti-cancer vaccines promise novel and more effective cancer treatments.