Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and paranasal sinuses. Eosinophilic inflammation is described as a common endotype. The anti-interleukin-5 (IL-5) antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe CRSwNP when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, therapy monitoring and follow-up documentation are required, and therapy discontinuation has not been adequately established yet. In this paper, recommendations for monitoring the course and efficacy of therapy as well as for reviewing the duration and possible termination of therapy are provided. For this purpose, a literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching MEDLINE, PubMed, and the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including October 2022 were considered. Based on the international literature and previous experience, recommendations for follow-up, adherence to therapy intervals and possible therapy breaks, as well as termination of therapy when using mepolizumab for the indication CRSwNP in the German health care system are given by an expert panel on the basis of a documentation sheet.

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Mitochondria are present in all mammalian cells except matured red blood cells. Mitochondria consist of several metabolic pathways for glucose, fatty acids, amino acids, and bioenergetic pathways for ATP synthesis, membrane potential, and reactive oxygen production. In the liver, hepatic mitochondria play a key role in hepatic steatosis because mitochondrial metabolism produces acetyl-CoA which is the building block for synthesis of lipids and cholesterol. Mitochondria inner membrane is impermeable of metabolites, reducing equivalents, and small molecules such as phosphate, and sulfate. Thus, mitochondrial shuttles and carriers function as the routes of influx and efflux of these metabolites and molecules across the inner membrane. The signal regulation of these shuttles and mitochondrial enzymes could play a key role in coordinating the mitochondrial metabolism to adapt the cytosolic part of metabolic pathways in liver metabolic stress. Intriguingly, the interaction of mitochondria protein SH3 domain-binding protein 5 (SAB/SH3BP5) and c-Jun N-terminal kinase (JNK) was found as a pivotal role in sustained activation of JNK and phosphorylated-JNK (P-JNK) mediated activation of lipogenic pathway in nutritional excess. Knockout or knockdown of SAB prevented or reversed the hepatic steatosis, inflammation, and fibrosis, and improved metabolic intolerance and energy expenditure. Moreover, blocking the SAB peptide prevents palmitic acid-induced P-JNK interaction with SAB and inhibition of mitochondrial bioenergetics, implying the P-JNK effect on mitochondrial metabolism. This review focuses on the flow of mitochondrial metabolites in metabolic stress conditions and the contribution of mitochondria and mitochondrial stress signals in hepatic steatosis.

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Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline alterations in mismatch repair (MMR) genes leading to increased risk of colon cancer as well as other cancer types. Non-small cell lung cancer (NSCLC) is not among typical Lynch syndrome-associated tumors: pembrolizumab, an immune checkpoint inhibitor, is actually approved for the treatment of NSCLC patients and represents a promising treatment option for patients with advanced metastatic MMR-deficient cancer, regardless of tumor origin. This case report describes the clinical presentation and management of a 74-year-old female with a history of rectal adenocarcinoma and ovarian cancer, who has a documented frameshift pathogenic variant in the exon 8 of MSH6 gene and an intronic variant in the BRCA2 gene (classified as a variant of uncertain significance), affected by NSCLC with brain metastases. Despite these premises, the patient was treated with pembrolizumab and she did not benefit from this kind of treatment.

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In spite of the immense advancement in the diagnostic and treatment modalities, cancer continues to be one of the leading causes of mortality across the globe, responsible for the death of around 10 million patients every year. The foremost challenges faced in the treatment of this disease are chemoresistance, adverse effects of the drugs, and the high cost of treatment. Though scientific studies over the past few decades have foreseen and are focusing on the cancer-preventive and therapeutic potential of natural products and their underlying mechanism of action, many more of these agents are not still explored. Piperlongumine (PL), or piplartine, is one such alkaloid isolated from Piper longum Linn., which is shown to be safe and has significant potential in the prevention and therapy of cancer. Numerous shreds of evidence have established the ability of this alkaloid and its analogs and nanoformulations in modulating various complex molecular pathways such as phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin, nuclear factor-kappa B, Janus kinases/signal transducer and activator of transcription 3, etc. and inhibit different hallmarks of cancer such as cell survival, proliferation, invasion, angiogenesis, epithelial-mesenchymal-transition, metastases, etc. In addition, PL was also shown to inhibit radioresistance and chemoresistance and sensitize the cancer cells to the standard chemotherapeutic agents. Therefore, this compound has high potential as a drug candidate for the prevention and treatment of different cancers. The current review briefly reiterates the anti-cancer properties of PL against different types of cancer, which permits further investigation by conducting clinical studies.

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Bone formation is a complex process that occurs throughout life, and is normally limited to the skeletal system. In bone formation, osteoprogenitor cells follow several developmental stages, including differentiation in osteoblasts, proliferation, matrix maturation, and mineralization. The mechanisms involved in the mineralization process of bone, such as in the new bone formation, are extremely complex and have been under intense investigation for many years. Bone formation follows two distinct processes, intramembranous and endochondral ossification; both are regulated by signaling pathways involving numerous genes. Disturbance of these signaling pathways may cause a large spectrum of skeletal diseases characterized by new bone formation and bone growth anomalies. This review will only focus on the key genetic pathways involved in heterotopic bone formation. Wingless/integrated (Wnt), hedgehog (HH), and transforming growth factor beta (TGFβ)/bone morphogenetic protein (BMP) signaling pathways are described and illustrated; their relation with new bone formation is demonstrated through their involvement in bone formation disorders.

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Messenger RNA (mRNA) has recently made important progress in clinical implementation, offering a promising therapeutic option for infectious disease and cancer. However, the nature of mRNA molecules rendered them poorly bioavailable and unstable in vivo, impeding their further clinical application. Therefore, safe and efficient delivery of mRNA therapeutics to the target site is crucial for their successful translation into the clinical setting. Various vectors have been explored for mRNA delivery. Among them, polyesters and their analogs, a family of biodegradable polymers, have exhibited great potential for mRNA delivery. In this short review, the authors briefly introduce mRNA therapeutics, their therapeutic applications and delivery challenges. The authors then presented the typical examples of polyester materials for mRNA delivery to highlight the current progress and discuss the challenges for the rational design of polyester based mRNA delivery vectors. The authors hope to provide a new insight for the design of biodegradable vectors for nucleic acids delivery, thereby promoting their further clinic translation.

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Cancer immunotherapy has emerged as a groundbreaking field, offering promising and transformative tools for oncological research and treatment. However, it faces several limitations, including variations in cancer types, dependence on the tumor microenvironments (TMEs), immune cell exhaustion, and adverse reactions. Magnetic nanoparticles, particularly magnetite nanoparticles (MNPs), with established pharmacodynamics and pharmacokinetics for clinical use, hold great promise in this context and are now being explored for therapeutic aims. Numerous preclinical studies have illustrated their efficacy in enhancing immunotherapy through various strategies, such as modulating leukocyte functions, creating favorable TMEs for cytotoxic T lymphocytes, combining with monoclonal antibodies, and stimulating the immune response via magnetic hyperthermia (MHT) treatment (Front Immunol. 2021;12:701485. doi: 10.3389/fimmu.2021.701485). However, the current clinical trials of MNPs are mostly for diagnostic aims and as a tool for generating hyperthermia for tumor ablation. With concerns about the adverse effects of MNPs in the in vivo systems, clinical translation and clinical study of MNP-boosted immunotherapy remains limited. The lack of extensive clinical investigations poses a current barrier to patient application. Urgent efforts are needed to ascertain both the efficacy of MNP-enhanced immunotherapy and its safety profile in combination therapy. This article reviews the roles, potential, and challenges of using MNPs in advancing cancer immunotherapy. The application of MNPs in boosting immunotherapy, and its perspective role in research and development is also discussed.

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Immunotherapy is a unique approach to treat cancer that targets tumours besides triggering the immune cells. It attempts to harness the supremacy and specificity of immune cells for the regression of malignancy. The key strategy of immunotherapy is that it boosts the natural defence and manipulates the immune system at both cellular and molecular levels. Long-lasting anti-tumour response, reduced metastasis, and recurrence can be achieved with immunotherapy than conventional treatments. For example, targeting cytotoxic T-lymphocyte antigen-4 (CTLA4) by monoclonal antibody is reported as an effective strategy against cancer progression in vivo and chimeric antigen receptor (CAR) modified T-cells are known to express a stronger anti-tumour activity. CTLA4 and CAR are, therefore, beneficial in cancer immunotherapy; however, in clinical settings, both are expensive and cause adverse side effects. Nanomaterials have augmented advantages in cancer immunotherapy, besides their utility in effective delivery and diagnostics. In particular, materials based on lipids, polymers, and metals have been sought-after for delivery technologies. Moreover, the surface of nanomaterials can be engineered using ligands, antigens, and antibodies to target immune cells. In this sense, checkpoint inhibitors, cytokines, agonistic antibodies, surface receptors, and engineered T-cells are promising to regulate the immune system against tumours. Therefore, emerging nanomaterials that can be used for the treatment of cancer is the prime focus of this review. The correlation of mode of administration and biodistribution of various nanomaterials is reviewed here. Besides, the acute and chronic side effects and outcome of clinical trials in the context of cancer immunotherapy are discussed.

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Steroid use is a widely accepted practice for both the treatment and prevention of tumor-induced edema, but there are many unknowns regarding their current clinical utility with modern anti-tumor therapies. This decreases edema and relieves the symptomatic mass effect. There are clearly understood benefits and commonly accepted complications of methylprednisolone (MP) use, but the topic is recently controversial. With immunotherapy advancing, a robust immune response is crucial for full therapeutic efficacy. The immunosuppression of MP may interfere with future and current therapeutics relying on the integrity of the patient’s immune system. This further emphasizes the need for alternative agents to effectively treat tumor-induced cerebral edema. This review highlights the current clinical utility of steroids to treat brain tumor-related edema and the underlying pathophysiology. It also reviews details regarding different steroid formulations and dosing. Research available regarding concurrent steroid use with immunotherapy is detailed next, followed by alternatives to steroids and barriers to their adoption. Finally, this paper discusses pre-clinical findings and emerging treatments aimed to augment or replace steroid use.

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