The molecular mechanisms of various long non-coding RNA (lncRNA) in human lung tumors: Shedding light on the molecular mechanisms.

Although it is still mostly incomplete, unraveling the gene expression networks controlling the initiation and progression of cancer is crucial. The rapid identification and characterization of long noncoding RNAs (lncRNAs) is made possible by advancements in computational biology and RNA-seq technology. According to recent research, lncRNAs are involved in several stages in the genesis of lung cancer. These lncRNAs interact with DNA, RNA, protein molecules, and/or their combinations. They play a crucial role in transcriptional and post-transcriptional regulation, as well as chromatin architecture. Their misexpression gives cancer cells the ability to start, grow, and spread tumors. This review will focus on their abnormal expression and function in lung cancer, as well as their involvement in cancer therapy and diagnosis.

Mesenchymal stem cells and their extracellular vesicles as emerging therapeutic tools in the treatment of ischemic stroke.

Ischemic stroke (IS) is a neurological condition characterized by severe long-term consequences and an unfavorable prognosis for numerous patients. Despite advancements in stroke treatment, existing therapeutic approaches possess certain limitations. However, accumulating evidence suggests that mesenchymal stem/stromal cells (MSCs) hold promise as a potential therapy for various neurological disorders, including IS, owing to their advantageous properties, such as immunomodulation and tissue regeneration. Additionally, MSCs primarily exert their therapeutic effects through the release of extracellular vesicles (EVs), highlighting the significance of their paracrine activities. These EVs are small double-layered phospholipid membrane vesicles, carrying a diverse cargo of proteins, lipids, and miRNAs that enable effective cell-to-cell communication. Notably, EVs have emerged as attractive substitutes for stem cell therapy due to their reduced immunogenicity, lower tumorigenic potential, and ease of administration and handling. Hence, this review summarizes the current preclinical and clinical studies performed to investigate the safety and therapeutic potential of MSCs and their EVs derived from different sources, including bone marrow, adipose tissue, umbilical cord blood, and Wharton's jelly in IS.

Overcoming drug resistance with specific nano scales to targeted therapy: Focused on metastatic cancers.

Metastatic cancer, which accounts for the majority of cancer fatalities, is a difficult illness to treat. Currently used cancer treatments include radiation therapy, chemotherapy, surgery, and targeted treatment (immune, gene, and hormonal). The disadvantages of these treatments include a high risk of tumor recurrence and surgical complications that may result in permanent deformities. On the other hand, most chemotherapy drugs are small molecules, which usually have unfavorable side effects, low absorption, poor selectivity, and multi-drug resistance. Anticancer drugs can be delivered precisely to the cancer spot by encapsulating them to reduce side effects. Stimuli-responsive nanocarriers can be used for drug release at cancer sites and provide target-specific delivery. As previously stated, metastasis is the primary cause of cancer-related mortality. We have evaluated the usage of nano-medications in the treatment of some metastatic tumors.

lncRNA-microRNA axis in cancer drug resistance: particular focus on signaling pathways.

Cancer drug resistance remains a formidable challenge in modern oncology, necessitating innovative therapeutic strategies. The convergence of intricate regulatory networks involving long non-coding RNAs, microRNAs, and pivotal signaling pathways has emerged as a crucial determinant of drug resistance. This review underscores the multifaceted roles of lncRNAs and miRNAs in orchestrating gene expression and cellular processes, mainly focusing on their interactions with specific signaling pathways. Dysregulation of these networks leads to the acquisition of drug resistance, dampening the efficacy of conventional treatments. The review highlights the potential therapeutic avenues unlocked by targeting these non-coding RNAs. Developing specific inhibitors or mimics for lncRNAs and miRNAs, alone or in combination with conventional chemotherapy, emerges as a promising strategy. In addition, epigenetic modulators, immunotherapies, and personalized medicine present exciting prospects in tackling drug resistance. While substantial progress has been made, challenges, including target validation and safety assessment, remain. The review emphasizes the need for continued research to overcome these hurdles and underscores the transformative potential of lncRNA-miRNA interplay in revolutionizing cancer therapy.

Effective extracellular vesicles in glioma: Focusing on effective ncRNA exosomes and immunotherapy methods for treatment.

This comprehensive article explores the complex field of glioma treatment, with a focus on the important roles of non-coding RNAsRNAs (ncRNAs) and exosomes, as well as the potential synergies of immunotherapy. The investigation begins by examining the various functions of ncRNAs and their involvement in glioma pathogenesis, progression, and as potential diagnostic biomarkers. Special attention is given to exosomes as carriers of ncRNAs and their intricate dynamics within the tumor microenvironment. The exploration extends to immunotherapy methods, analyzing their mechanisms and clinical implications in the treatment of glioma. By synthesizing these components, the article aims to provide a comprehensive understanding of how ncRNAs, exosomes, and immunotherapy interact, offering valuable insights into the evolving landscape of glioma research and therapeutic strategies.

Investigating the Effect of Cigarette Smoking on Serum Uric Acid Levels in Multiple Sclerosis Patients: A Cross Sectional Study.

OBJECTIVES: The present study is aimed at determining the effect of cigarette smoking (CS) on serum uric acid (UA) levels quantitatively before and after smoking cessation among people with MS (pwMS). Additionally, a possible correlation between UA levels and both disability progression and disease severity was also investigated. A retrospective cross-sectional study was conducted using the Nottingham University Hospitals MS Clinics database. It involves 127 people with definite MS recorded when reporting the latest smoking status and the clinical diagnosis. All necessary demographics and clinical characteristics were collected. We found that smoker pwMS had significantly lower serum UA levels than non-smoker pwMS (p-value = 0.0475), and this reduction was recovered after smoking cessation (p-value = 0.0216). However, the levels of disability or disease severity were not correlated with the levels of serum UA in current smoker pwMS, measured by the expanded disability status scale (EDSS; r = -0.24; p-value = 0.38), multiple sclerosis impact scale 29 (MSIS-29; r = 0.01; p-value = 0.97) and MS severity score (MSSS; r = -0.16; p-value = 0.58), respectively. Our result suggests that the reduction in UA levels is more likely a consequence of oxidative stress triggered by many risk factors, including CS, and could be considered a potential indicator of smoking cessation. In addition, the absence of a correlation between UA levels and disease severity and disability suggests that UA is not an optimal biomarker for disease severity and disability prediction among current smoker, ex-smoker or non-smoker pwMS.

Chitosan modified 5-fluorouracil nanostructured lipid carriers for treatment of diabetic retinopathy in rats: A new dimension to an anticancer drug.

Diabetic retinopathy (DR) is one of the chronic complications of diabetes. It includes retinal blood vessels' damage. If untreated, it leads to loss of vision. The existing treatment strategies for DR are expensive, invasive, and need expertise during administration. Hence, there is a need to develop a non-invasive topical formulation that can penetrate deep to the posterior segment of retina and treat the damaged retinal vessels. In addition, it should also provide sustained release. In recent years, novel drug delivery systems (NDDS) have been explored for treating DR and found successful. In this study, chitosan (CS) modified 5-Fluorouracil Nanostructured Lipid Carriers (CS-5-FU-NLCs) were prepared by modified melt emulsification-ultrasonication method and optimized by Box-Behnken Design. The size, polydispersity index, zeta potential and entrapment efficiency of CS-5-FU-NLCs were 163.2 ± 2.3 nm, 0.28 ± 1.52, 21.4 ± 0.5 mV and 85.0 ± 0.2 %, respectively. The in vitro drug release and ex vivo permeation study confirmed higher and sustained drug release in CS-5-FU-NLCs as compared to 5-FU solution. HET-CAM Model ensured the non-irritant nature of CS-5-FU-NLCs. In vivo ocular studies of CS-5-FU-NLCs confirmed antiangiogenic effect of 5-FU by CAM model and diabetic retinopathy induced rat model, indicating successful delivery of 5-FU to the retina.

The role of hesperidin as a cardioprotective strategy against doxorubicin-induced cardiotoxicity: The antioxidant, anti-inflammatory, antiapoptotic, and cytoprotective potentials.

Background: Doxorubicin (DOX), an anthracycline antibiotic, is a powerful chemotherapeutic agent effective against multiple types of cancer, particularly lung, breast, bladder and hematologic neoplasia (lymphomas and leukemia). However, its therapeutic usage is restricted by its known cardiotoxicity, which is associated with the production of oxidative stress. Enhancing antioxidant capacity represents a promising approach to mitigate DOX-induced cardiotoxicity. Hesperidin (HES), a citrus bioflavonoid, possesses several pharmacological effects, such as anti-inflammatory and antioxidant characteristics. Aim: This study was designed to evaluate the cardiotoxicity of DOX and assess the possible cardioprotective role of HES. Methods: Groups of Wistar rats were either treated with DOX (4 mg/kg. bw., once a week for five consecutive weeks, intraperitoneally) or received co-treatment with HES (100 mg/kg. bw./day in distilled water, 5 days in a week for five consecutive weeks, administered orally). Heart and blood samples were obtained for histological, immunohistochemical, and biochemical assessments. Results: DOX administration resulted in severe cardiotoxicity, as evidenced by significant elevations in cardiac biomarkers, including Troponin I (CTnI), Creatine kinase (CK-Total), Creatine kinase isoenzyme-MB (CK-MB), lactate dehydrogenase (LDH), and Aspartate aminotransferase (AST). DOX also elevated pro-inflammatory cytokines, such as Interferon γ (IFN-γ), Interleukin 1ß (IL-1ß), and Tumor necrosis factor α (TNF-α). Furthermore, DOX-induced oxidative stress and substantially reduced the levels of antioxidant enzymes, including Glutathione peroxidase (GPX), Superoxide dismutase (SOD), and Catalase (CAT). Histopathologically, DOX caused severe Zenker's necrosis, cardiomyocyte disarray, sarcoplasmic vacuolizations, cardiomyocyte congestion, and inflammatory cell infiltration. Immunohistochemically, DOX exhibited extensive apoptosis, as indicated by strong positive immuno-localization against anti-caspase-3 antibody. In contrast, co-treatment with HES protected cardiac tissues against cardiotoxicity of DOX, as indicated by the amelioration of histological abnormalities and the normalization of biochemical values. Conclusion: We can conclude that DOX induces severe cardiotoxicity characterized by oxidative stress, inflammation, pathological alterations, and apoptosis. Co-treatment with HES demonstrates significant cardioprotective effects by virtue of its potent anti-inflammatory, antioxidant, cytoprotective, and antiapoptotic characteristics.

Inhibition of Chk2 promotes neuroprotection, axon regeneration, and functional recovery after CNS injury.

DNA double-strand breaks occur in many acute and long-term neurological conditions, including neurodegeneration, neurotrauma, and stroke. Nonrepaired breaks chronically activate the DNA damage response in neurons, leading to neural dysfunction and apoptosis. Here, we show that targeting of the central ATM-Chk2 pathway regulating the response to double-strand breaks slows neural decline in Drosophila models of chronic neurodegeneration. Inhibitors of ATM-Chk2, but not the parallel ATR-Chk1 pathway, also promote marked, functional recovery after acute central nervous system injury in rats, suggesting that inhibiting nonhomologous end-joining rather than homologous recombination is crucial for neuroprotection. We demonstrate that the Chk2 inhibitor, prexasertib, which has been evaluated in phase 2 clinical trials for cancer, has potent neuroprotective effects and represents a new treatment option to promote functional recovery after spinal cord or optic nerve injury.

Pimitespib, an HSP90 inhibitor, augments nifuroxazide-induced disruption in the IL-6/STAT3/HIF-1α autocrine loop in rats with bleomycin-challenged lungs: Evolutionary perspective in managing pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a fatal lung disorder in which the etiology and pathogenesis are still unobvious. Effective treatments are urgently needed considering that lung transplantation is the only treatment that could improve outcomes. This study aimed to investigate the therapeutic significance of the dual administration of pimitespib, an HSP90 inhibitor, and nifuroxazide, a STAT3 inhibitor, against bleomycin-induced pulmonary fibrosis in rats. Our results revealed that pimitespib/nifuroxazide inhibited bleomycin-induced alterations in the structure and the function of the lungs. They demonstrated significant decreases in the BALF total and differential cell counts, LDH activity, and total protein. Concurrently, there was a reduction in the accumulation of collagen as proved by decreased hydroxyproline and the gene expression of COL1A1 accompanied by lower levels of PDGF-BB, TIMP-1, and TGF-ß. The levels of IL-6 were also downregulated. Pimitespib-induced inhibition of HSP90 led to subsequent inhibition of HIF-1α and STAT3 client proteins since the closed HSP90 would not enclose its client proteins. Therefore, pimitespib resulted in the repression of HIF-1α/CREB-p300 HAT as well as the STAT3/CREB-p300 HAT nuclear interactions. On the other hand, nifuroxazide resulted in a notable decline in pSTAT3 and HIF-1α levels. Subsequently, the combined effects of both drugs led to a substantial reduction in ECM deposition. Herein, pimitespib augmented nifuroxazide-induced disruption in the IL-6/STAT3/HIF-1α autocrine loop. Our findings also disclose that this novel loop is a promising therapeutic attack site for possible pulmonary fibrosis repression studies. Therefore, the use of pimitespib/nifuroxazide embodies an evolutionary perspective in managing pulmonary fibrosis.

Diacetylrhein, an anthraquinone antiarthritic agent, suppresses dextran sodium sulfate-induced inflammation in rats: A possible mechanism for a protective effect against ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory life-threatening and premalignant disorder with no cure that even might end up with surgical removal of a large section or even all of the colon. It is characterized by relapsing-remitting courses of intestinal inflammation and mucosal damage in which oxidative stress and exaggerated inflammatory response play a significant role. Most of the current medications to maintain remission are symptomatic and have many adverse reactions. Therefore, the potential for improved management of patients with UC continues to increase. Yet, the benefits of using the antiarthritic agent diacetylrhein to counteract inflammation in UC are still obscure. Hence, our study was designed to explore its potential role in UC using a model of dextran sodium sulfate-induced acute colitis in rats. Our results revealed that diacetylrhein targeted the NLRP3 and inhibited the inflammasome assembly. Consequently, caspase-1 activity and the inflammatory cytokines IL-1ß and IL-18 were inhibited leading to a curbed pyroptosis process. Additionally, diacetylrhein revealed a significant antiapoptotic potential as revealed by the levels of pro-apoptotic and anti-apoptotic proteins. Concomitant to these effects, diacetylrhein also interrupted NFκB signals leading to improved microscopic features of inflamed colon and decreased colon weight to length ratio, indices of disease activity, and macroscopic damage. Additionally, a reduction in the myeloperoxidase activity, IL-6, and TGF-ß alongside an increase in the gene expression of Ocln and ZO-1 were detected. To conclude diacetylrhein showed a significant antioxidant and anti-inflammatory potential and therefore might represent a promising agent in the management of acute UC.