Role of immunotherapies and stem cell therapy in the management of liver cancer: A comprehensive review.

Liver cancer (LC) is the sixth most common disease and the third most common cause of cancer-related mortality. The WHO predicts that more than 1 million deaths will occur from LC by 2030. Hepatocellular carcinoma (HCC) is a common form of primary LC. Today, the management of LC involves multiple disciplines, and multimodal therapy is typically selected on an individual basis, considering the intricate interactions between the patient's overall health, the stage of the tumor, and the degree of underlying liver disease. Currently, the treatment of cancers, including LC, has undergone a paradigm shift in the last ten years because of immuno-oncology. To treat HCC, immune therapy approaches have been developed to enhance or cause the body's natural immune response to specifically target tumor cells. In this context, immune checkpoint pathway inhibitors, engineered cytokines, adoptive cell therapy, immune cells modified with chimeric antigen receptors, and therapeutic cancer vaccines have advanced to clinical trials and offered new hope to cancer patients. The outcomes of these treatments are encouraging. Additionally, treatment using stem cells is a new approach for restoring deteriorated tissues because of their strong differentiation potential and capacity to release cytokines that encourage cell division and the formation of blood vessels. Although there is no proof that stem cell therapy works for many types of cancer, preclinical research on stem cells has shown promise in treating HCC. This review provides a recent update regarding the impact of immunotherapy and stem cells in HCC and promising outcomes.

An optimized design for motivated broadband LPDA antenna.

This paper presents a super wideband and high-gain log periodic dipole array (LPDA) antenna. The overall structure of the antenna was constructed using microwave studio computer simulation technology. The optimal sizes of the planned antenna are 39 × 10× 0.254 mm3. The engineered antenna arrangement is implemented on an RT5880 substrate as a dielectric medium. The LPDA is arranged in four arms that are equally spaced on both lines. The main 50Ω feeder line is partially grounded at the back of the substrate. A combination of circular director units is being studied and tuned in a regular pattern at a predefined distance from the antenna. An improvement in gain of 3 dBi is the response of the director units. The Conformist LPDA is adjusted to achieve a wide range of millimeter wave bands ranging from 40 to over 70 GHz. The antenna resonates at 60 GHz, where the maximum realized gain of 14.97 dBi is attained. The antenna was tested for utilization in the V-band involving wireless personal area network (WPAN) applications recommended by IEEE 802.11ad and IEEE 802.15.3c. The outcomes of the constructed antenna elements' tests and simulations agree fairly well. The proposed layout works better than previous efforts in this field.

Stem Cells Reprogramming in Diabetes Mellitus and Diabetic Complications: Recent Advances.

BACKGROUND: The incidence of diabetes mellitus (DM) is dramatically increasing worldwide, and it is expected to affect 700 million cases by 2045. Diabetes influences health care economics, human quality of life, morbidity, and mortality, which were primarily seen extensively in developing countries. Uncontrolled DM, which results in consistent hyperglycemia, may lead to severe life-threatening complications such as nephropathy, retinopathy, neuropathy, and cardiovascular complications. METHODOLOGY: In addition to traditional therapies with insulin and oral anti-diabetics, researchers have developed new approaches for treatment, including stem cell (SC) therapy, which exhibits promising outcomes. Besides its significant role in treating type one DM (T1DM) and type two DM (T2DM), it can also attenuate diabetic complications. Furthermore, the development of insulin-producing cells can be achieved by using the different types of SCs, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and multiple types of adult stem cells, such as pancreatic, hepatic, and mesenchymal stem cells (MSC). All these types have been extensively studied and proved their ability to develop insulin-producing cells, but every type has limitations. CONCLUSION: This review aims to enlighten researchers about recent advances in stem cell research and their potential benefits in DM and diabetic complications.

Baicalin and lung diseases.

Studies focusing on natural products have been conducted worldwide, and the results suggest that their natural ingredients effectively treat a wide range of illnesses. Baicalin (BIA) is a glycoside derived from the flavonoid baicalein present in Scutellaria baicalensis of the Lamiaceae family. Interestingly, BIA has been shown to protect the lungs in several animal models used in numerous studies. Therefore, we fully analyzed the data of the studies that focused on BIA's lung protective function against various injuries and included them in this review. Interestingly, BIA exhibits promising effects against acute lung injury, lung fibrosis, pulmonary embolism, and lung remodelling associated with COPD, LPS, and paraquat insecticide. BAI exhibits anticancer activity against lung cancer. Additionally, BIA potently attenuates lung damage associated with infections. BIA primarily exerts its therapeutic effects by suppressing inflammation, oxidative stress immune response, and apoptosis pathways. Nrf2/HO-1, PI3K/Akt, NF-κB, STAT3, MAPKs, TLR4, and NLRP3 are important targets in the pulmonary therapeutic effects of BIA on different lung disease models. Consequently, we recommend using it in future potential clinical applications, its contribution to treatment guidelines, and translating its promising effects to clinical practice in lung diseases.

Pharmacological update of mirtazapine: a narrative literature review.

Mirtazapine (MTZ) is an antidepressant drug with an exceptional pharmacological profile. It also has an excellent safety and tolerability profile. The present review provides a pharmacological update on MTZ and summarizes the research findings of MTZ's effects on different diseases. MTZ is hypothesized to have antidepressant effects because of the synergy between noradrenergic and serotonergic actions and is effective in treating major depressive disorder and depression associated with epilepsy, Alzheimer's disease, stroke, cardiovascular disease, and respiratory disease. In cancer patients, MTZ significantly reduced sadness, nausea, sleep disruption, and pain and improved quality of life. Also, it has promising effects on Parkinson's disease, schizophrenia, dysthymia, social anxiety disorder, alcohol dependency, posttraumatic stress disorder, panic disorder, pain syndromes, obsessive-compulsive disorder, and sleep disorders. Additionally, MTZ is potentially therapeutic in different situations associated with depression, such as liver, kidney, cardiovascular, respiratory, infertility, heavy metal-induced neurotoxicity, and pruritus. Potent antioxidative, anti-inflammatory, and anti-apoptotic bioactivities mediate these promising effects. These positive outcomes of the scientific investigations motivate more and more clinical trials for a golden exceptional antidepressant in different conditions.

Targeting necroptosis in fibrosis.

Necroptosis, a type of programmed cell death that resembles necrosis, is now known to depend on a different molecular mechanism from apoptosis, according to several recent studies. Many efforts have reported the possible influence of necroptosis in human disorders and concluded the crucial role in the pathophysiology of various diseases, including liver diseases, renal injuries, cancers, and others. Fibrosis is the most common end-stage pathological cascade of several chronic inflammatory disorders. In this review, we explain the impact of necroptosis and fibrosis, for which necroptosis has been demonstrated to be a contributing factor. We also go over the inhibitors of necroptosis and how they have been applied to fibrosis models. This review helps to clarify the role of necroptosis in fibrosis and will encourage clinical efforts to target this pathway of programmed cell death.

Nrf2/HO-1 as a therapeutic target in renal fibrosis.

Chronic kidney disease (CKD) is one of the most prevalent chronic diseases and affects between 10 and 14 % of the world's population. The World Health Organization estimates that by 2040, the disease will be fifth in prevalence. End-stage CKD is characterized by renal fibrosis, which can eventually lead to kidney failure and death. Renal fibrosis develops due to multiple injuries and involves oxidative stress and inflammation. In the human body, nuclear factor erythroid 2-related factor 2 (Nrf2) plays an important role in the expression of antioxidant, anti-inflammatory, and cytoprotective genes, which prevents oxidative stress and inflammation damage. Heme oxygenase (HO-1) is an inducible homolog influenced by heme products and after exposure to cellular stress inducers such as oxidants, inflammatory chemokines/cytokines, and tissue damage as an outcome or downstream of Nrf2 activation. HO-1 is known for its antioxidative properties, which play an important role in regulating oxidative stress. In renal diseases-induced tissue fibrosis and xenobiotics-induced renal fibrosis, Nrf2/HO-1 has been targeted with promising results. This review summarizes these studies and highlights the interesting bioactive compounds that may assist in attenuating renal fibrosis mediated by HO-1 activation. In conclusion, Nrf2/HO-1 signal activation could have a renoprotective effect strategy against CKD caused by oxidative stress, inflammation, and consequent renal fibrosis.

Pharmacological updates of nifuroxazide: Promising preclinical effects and the underlying molecular mechanisms.

Nifuroxazide (NFX) is a safe nitrofuran antibacterial drug used clinically to treat acute diarrhea and infectious traveler diarrhea or colitis. Recent studies revealed that NFX displays multiple pharmacological effects, including anticancer, antioxidant, and anti-inflammatory effects. NFX has potential roles in inhibiting thyroid, breast, lung, bladder, liver, and colon cancers and osteosarcoma, melanoma, and others mediated by suppressing STAT3 as well as ALDH1, MMP2, MMP9, Bcl2 and upregulating Bax. Moreover, it has promising effects against sepsis-induced organ injury, hepatic disorders, diabetic nephropathy, ulcerative colitis, and immune disorders. These promising effects appear to be mediated by suppressing STAT3 as well as NF-κB, TLR4, and ß-catenin expressions and effectively decreasing downstream cytokines TNF-α, IL-1ß, and IL-6. Our review summarizes the available studies on the molecular biological mechanisms of NFX in cancer and other diseases and it is recommended to translate the studies in experimental animals and cultured cells and repurpose NFX in various diseases for scientific evidence based on human studies.

The molecular mechanisms underlying anti-inflammatory effects of galangin in different diseases.

When used as an alternative source of drugs to treat inflammation-associated diseases, phytochemicals with anti-inflammatory properties provide beneficial impacts. Galangin is one of the most naturally occurring flavonoids. Galangin has many biological activities, such as anti-inflammatory, antioxidant, antiproliferative, antimicrobial, anti-obesity, antidiabetic, and anti-genotoxic activities. We observed that galangin was well tolerated and positively impacted disease underlying inflammation for the renal, hepatic, central nervous system, cardiovascular, gastrointestinal system, skin, and respiratory disorders, as well as ulcerative colitis, acute pancreatitis, retinopathy, osteoarthritis, osteoporosis, and rheumatoid arthritis. Galangin anti-inflammatory effects are mediated mainly by suppressing p38 mitogen-activated protein kinases, nuclear factor-kappa B, and nod-like receptor protein 3 signals. These effects are confirmed and supported by molecular docking. Clinical translational research is required to accelerate the bench-to-bedside transfer and determine whether galangin can be utilised as a safe, natural source of pharmaceutical anti-inflammatory medication for humans.

Therapeutic interventions target the NLRP3 inflammasome in ulcerative colitis: Comprehensive study.

One of the significant health issues in the world is the prevalence of ulcerative colitis (UC). UC is a chronic disorder that mainly affects the colon, beginning with the rectum, and can progress from asymptomatic mild inflammation to extensive inflammation of the entire colon. Understanding the underlying molecular mechanisms of UC pathogenesis emphasizes the need for innovative therapeutic approaches based on identifying molecular targets. Interestingly, in response to cellular injury, the NLR family pyrin domain containing 3 (NLRP3) inflammasome is a crucial part of the inflammation and immunological reaction by promoting caspase-1 activation and the release of interleukin-1ß. This review discusses the mechanisms of NLRP3 inflammasome activation by various signals and its regulation and impact on UC.

Promising hepatoprotective effects of lycopene in different liver diseases.

The incidence of liver diseases such as hepatitis, fibrosis, cirrhosis, and liver cancer is one of the world's most significant health challenges. Liver diseases can be caused by a variety of circumstances, including viral infection, exposure to xenobiotics, environmental pollutants, metabolic disorders, and others. Lycopene (LYC) is a potent antioxidant of the carotenoid family in red fruits and vegetables. LYC has been found to have multiple biological activities, including antioxidative, anti-inflammatory, and antiapoptotic effects. Notably, LYC has promised hepatoprotective properties against various liver diseases, including alcoholic liver disease, nonalcoholic fatty liver disease, liver fibrosis, hepatic ischemia/reperfusion injury, hepatocellular carcinoma, fulminant hepatic failure, and radiation-induced liver damage. It also protects against drug-induced liver injury caused by tramadol, cisplatin, methotrexate, oestrogen, sulfamethoxazole, and others. Moreover, promising hepatoprotective effects of LYC in environmental toxins such as Di(2-ethylhexyl) phthalate, atrazine, aflatoxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin, bisphenol A, dichlorvos as well as heavy metals. Our review aims to discuss LYC's hepatoprotective properties and explore the mechanisms behind this effect. It highlights several research directions for further investigating the potential benefits of LYC consumption in treating human liver diseases.

Protective effects of berberine on various kidney diseases: Emphasis on the promising effects and the underlined molecular mechanisms.

Berberine (BBR) is a pentacyclic benzylisoquinoline alkaloid that can be found in diversity of medicinal plants. BBR has a wide range of pharmacological bioactivities, in addition when administrated orally, it has a broad safety margin. It has been used as an antidiarrheal, antimicrobial, and anti-diabetic drug in Ayurvedic and Chinese medicine. Several scholars have found that BBR has promising renoprotective effects against different renal illnesses, including diabetic nephropathy, renal fibrosis, renal ischemia, renal aging, and renal stones. Also, it has renoprotective effects against nephrotoxicity induced by chemotherapy, heavy metal, aminoglycosides, NSAID, and others. These effects imply that BBR has an evolving therapeutic potential against acute renal failure and chronic renal diseases. Hence, we report herein the beneficial therapeutic renoprotective properties of BBR, as well as the highlighted molecular mechanism. In conclusion, the studies discussed throughout this review will afford a comprehensive overview about renoprotective effect of BBR and its therapeutic impact on different renal diseases.

Pleural and serum markers for diagnosis of malignant pleural effusion.

BACKGROUND: Differentiation between benign and malignant exudative pleural effusion remains a clinical challenge. Recently, several markers have been reported to increase the diagnostic accuracy of malignant pleural effusion, with controversial results. METHODS: Patients with exudative pleural effusion were divided into 2 groups: a malignant pleural effusion group (39 patients) diagnosed by malignant cells in pleural fluid cytology or by malignant infiltration of the pleura on pleural biopsy, and a benign pleural effusion group (51 patients) with neither malignant cells in pleural fluid cytology nor malignant infiltration of the pleura on pleural biopsy. Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were determined in both serum and pleural fluid samples, using commercially available enzyme-linked immunosorbent assay kits. RESULTS: The etiology of malignant pleural effusion in the malignant group was breast cancer in 43.6% and bronchogenic carcinoma in 25.6%. There was a statistically significant difference between the 2 groups regarding sex, with more males in the benign group. There was no significant difference between groups regarding age. The median levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were higher in the malignant group than in the benign group, and the differences were highly significant in both pleural fluid (p < 0.001) and serum (p < 0.001). CONCLUSION: Matrix metaloproteinase-9 and tissue inhibitor of metalloproteinase-1 in serum and pleural fluid samples might be valuable markers for differentiating benign from malignant pleural effusions.

Early Autologous Blood-Patch Pleurodesis versus Conservative Management for Treatment of Secondary Spontaneous Pneumothorax.

BACKGROUND: Autologous blood-patch pleurodesis has been effectively utilized as a treatment option for the condition of secondary spontaneous pneumothorax (SSP). Moreover, it can be used with persistent air leak, with or without residual air space. However, there have been no robust reports for the optimal timing for autologous blood-patch pleurodesis. The aim of this study is to compare early autologous blood-patch pleurodesis with conservative management of SSP. METHODS: We conducted a randomized controlled study at the Menoufia University Hospital. A total of 47 patients with SSP were randomly allocated into two groups: group A (23 patients) received intrapleural instillation of 50 mL autologous blood 3 days after insertion of chest drain and group B (24 patients) managed conservatively. The duration required for air leak to seal, chest drainage duration, length of hospital stay, and the incidence of complications were compared and statistically analyzed. RESULTS: The duration of air leak, duration to drain removal, and length of hospital stay were all significantly shorter in group A than in group B. CONCLUSION: Early intrapleural instillation of autologous blood is successful in sealing air leak in patients with SSP with persistent air leak, who are not fit or not willing to undergo surgery. It is superior to conservative treatment or late instillation of autologous blood, even if their lungs are not fully expanded.

Povidone-iodine pleurodesis versus talc pleurodesis in preventing recurrence of malignant pleural effusion.

BACKGROUND: Malignant pleural effusions continue to be a common problem in patients with metastatic disease, leading to a significant reduction in quality of life with progressive dyspnea, dry cough, chest pain and reduced physical activity. This study was conducted to compare the efficacy, safety, and outcome of Talc Powder Pleurodesis (TPP) with Povidone-iodine Pleurodesis (PIP) through a chest drain as a palliative preventive treatment of recurrent malignant pleural effusion. METHODS: A total of 39 neoplastic patients with recurrent malignant pleural effusion were enrolled in a prospective randomized trial. Twenty-one patients received Talc pleurodesis (group A), and eighteen patients (group B) received Povidone-iodine pleurodesis. The continuous variables were expressed as mean values ± standard deviation (SD) and compared using the unpaired t-test. The discrete variables were expressed as percentage and compared using the chi-square test (χ(2)) test. p-values of less than 0.05 were considered significant. RESULTS: Our study included 11 males and 28 females, the mean age was (71.0 ± 5.0) years for group A and (70.9 ± 5.1) years for group B (non-significant). Post-procedure analgesic requirements were recorded in both groups. Four patients in each group had fever (>38°C) within 48 hours of the procedure. Both groups achieved good symptomatic relief. There were no in-hospital deaths. The mean post-procedure hospital stay was (4.7 ± 1.2) days for group A and (4.2 ± 1.0) for group B (non-significant). At follow-up recurrence of significant pleural effusion requiring intervention was noted in four and five patients in group A and group B, respectively (non-significant difference). CONCLUSION: Povidone-iodine pleurodesis can be considered as a good alternative to Talc pleurodesis for recurrent malignant pleural effusion. The drug is available, cost effective, safe and can be administered through an intercostal drain and repeated if necessary.