Revolutionizing Cancer Treatment: Unleashing the Power of Viral Vaccines, Monoclonal Antibodies, and Proteolysis-Targeting Chimeras in the New Era of Immunotherapy.

In the realm of cancer immunotherapy, a profound evolution has ushered in sophisticated strategies that encompass both traditional cancer vaccines and emerging viral vaccines. This comprehensive Review offers an in-depth exploration of the methodologies, clinical applications, success stories, and future prospects of these approaches. Traditional cancer vaccines have undergone significant advancements utilizing diverse modalities such as proteins, peptides, and dendritic cells. More recent innovations have focused on the physiological mechanisms enabling the human body to recognize and combat precancerous and malignant cells, introducing specific markers like peptide-based anticancer vaccines targeting tumor-associated antigens. Moreover, cancer viral vaccines, leveraging engineered viruses to stimulate immune responses against specific antigens, exhibit substantial promise in inducing robust and enduring immunity. Integration with complementary therapeutic methods, including monoclonal antibodies, adjuvants, and radiation therapy, has not only improved survival rates but also deepened our understanding of viral virulence. Recent strides in vaccine design, encompassing oncolytic viruses, virus-like particles, and viral vectors, mark the frontier of innovation. While these advances hold immense potential, critical challenges must be addressed, such as strategies for immune evasion, potential off-target effects, and the optimization of viral genomes. In the landscape of immunotherapy, noteworthy innovations take the spotlight from the use of immunomodulatory agents for the enhancement of innate and adaptive immune collaboration. The emergence of proteolysis-targeting chimeras (PROTACs) as precision tools for cancer therapy is particularly exciting. With a focus on various cancers, from melanoma to formidable solid tumors, this Review critically assesses types of cancer vaccines, mechanisms, barriers in vaccine therapy, vaccine efficacy, safety profiles, and immune-related adverse events, providing a nuanced perspective on the underlying mechanisms involving cytotoxic T cells, natural killer cells, and dendritic cells. The Review also underscores the transformative potential of cutting-edge technologies such as clinical studies, molecular sequencing, and artificial intelligence in advancing the field of cancer vaccines. These tools not only expedite progress but also emphasize the multidimensional and rapidly evolving nature of this research, affirming its profound significance in the broader context of cancer therapy.

Health economic burden of COVID-19 in Saudi Arabia.

Background: The coronavirus disease 2019 (COVID-19) pandemic has added a massive economic burden on health care systems worldwide. Saudi Arabia is one of the numerous countries that have been economically affected by this pandemic. The objective of this study was to provide real-world data on the health economic burden of COVID-19 on the Saudi health sector and assess the direct medical costs associated with the management of COVID-19. Methods: A retrospective cohort study was conducted based on data collected from patients hospitalized with COVID-19 across 10 institutions in eight different regions in Saudi Arabia. The study calculated the direct medical costs of all cases during the study period by using SAS statistical analysis software. These costs included costs directly related to medical services, such as the health care treatment, hospital stays, laboratory investigations, treatment, outcome, and other related care. Results: A total of 5,286 adult patients admitted with COVID-19 during the study period were included in the study. The average age of the patients was 54 years, and the majority were male (79%). Among the COVID-19 patients hospitalized in a general ward, the median hospital length of stay was 5.5 days (mean: 9.18 days), while the ICU stay was 4.2 days (mean: 7.94 days). The total medical costs for general ward and ICU patients were US$ 38,895 and US$ 24,207,296.9, respectively. The total laboratory investigations ranked as the highest-cost services US$ 588,975 followed by treatment US$ 3,886,509.8. Overall, the total cost of all medical services for patients hospitalized with COVID-19 was US$ 51,572,393.4. Conclusion: This national study found that COVID-19 was not only a serious concern for patients but also a serious economic burden on the health care system in Saudi Arabia.

Natural therapeutics and nutraceuticals for lung diseases: Traditional significance, phytochemistry, and pharmacology.

BACKGROUND: Lung diseases including chronic obstructive pulmonary disease (COPD), infections like influenza, acute respiratory distress syndrome (ARDS), asthma and pneumonia lung cancer (LC) are common causes of sickness and death worldwide due to their remoteness, cold and harsh climatic conditions, and inaccessible health care facilities. PURPOSE: Many drugs have already been proposed for the treatment of lung diseases. Few of them are in clinical trials and have the potential to cure infectious diseases. Plant extracts or herbal products have been extensively used as Traditional Chinese Medicine (TCM) and Indian Ayurveda. Moreover, it has been involved in the inhibition of certain genes/protiens effects to promote regulation of signaling pathways. Natural remedies have been scientifically proven with remarkable bioactivities and are considered a cheap and safe source for lung disease. METHODS: This comprehensive review highlighted the literature about traditional plants and their metabolites with their applications for the treatment of lung diseases through experimental models in humans. Natural drugs information and mode of mechanism have been studied through the literature retrieved by Google Scholar, ScienceDirect, SciFinder, Scopus and Medline PubMed resources against lung diseases. RESULTS: In vitro, in vivo and computational studies have been explained for natural metabolites derived from plants (like flavonoids, alkaloids, and terpenoids) against different types of lung diseases. Probiotics have also been biologically active therapeutics against cancer, anti-inflammation, antiplatelet, antiviral, and antioxidants associated with lung diseases. CONCLUSION: The results of the mentioned natural metabolites repurposed for different lung diseases especially for SARS-CoV-2 should be evaluated more by advance computational applications, experimental models in the biological system, also need to be validated by clinical trials so that we may be able to retrieve potential drugs for most challenging lung diseases especially SARS-CoV-2.

MXene (Ti3C2Tx)-Embedded Nanocomposite Hydrogels for Biomedical Applications: A Review.

Polymeric nanocomposites have been outstanding functional materials and have garnered immense attention as sustainable materials to address multi-disciplinary problems. MXenes have emerged as a newer class of 2D materials that produce metallic conductivity upon interaction with hydrophilic species, and their delamination affords monolayer nanoplatelets of a thickness of about one nm and a side size in the micrometer range. Delaminated MXene has a high aspect ratio, making it an alluring nanofiller for multifunctional polymer nanocomposites. Herein, we have classified and discussed the structure, properties and application of major polysaccharide-based electroactive hydrogels (hyaluronic acid (HA), alginate sodium (SA), chitosan (CS) and cellulose) in biomedical applications, starting with the brief historical account of MXene's development followed by successive discussions on the synthesis methods, structures and properties of nanocomposites encompassing polysaccharides and MXenes, including their biomedical applications, cytotoxicity and biocompatibility aspects. Finally, the MXenes and their utility in the biomedical arena is deliberated with an eye on potential opportunities and challenges anticipated for them in the future, thus promoting their multifaceted applications.

Microneedle-Based Natural Polysaccharide for Drug Delivery Systems (DDS): Progress and Challenges.

In this focused progress review, the most widely accepted methods of transdermal drug delivery are hypodermic needles, transdermal patches and topical creams. However, microneedles (MNs) (or microneedle arrays) are low-invasive 3D biomedical constructs that bypass the skin barrier and produce systemic and localized pharmacological effects. In the past, biomaterials such as carbohydrates, due to their physicochemical properties, have been extensively used to manufacture microneedles (MNs). Due to their wide range of functional groups, carbohydrates enable the design and development of tunable properties and functionalities. In recent years, numerous microneedle products have emerged on the market, although much research needs to be undertaken to overcome the various challenges before the successful introduction of microneedles into the market. As a result, carbohydrate-based microarrays have a high potential to achieve a future step in sensing, drug delivery, and biologics restitution. In this review, a comprehensive overview of carbohydrates such as hyaluronic acid, chitin, chitosan, chondroitin sulfate, cellulose and starch is discussed systematically. It also discusses the various drug delivery strategies and mechanical properties of biomaterial-based MNs, the progress made so far in the clinical translation of carbohydrate-based MNs, and the promotional opportunities for their commercialization. In conclusion, the article summarizes the future perspectives of carbohydrate-based MNs, which are considered as the new class of topical drug delivery systems.

Bioactive-Based Cosmeceuticals: An Update on Emerging Trends.

Cosmetic-containing herbals are a cosmetic that has or is claimed to have medicinal properties, with bioactive ingredients purported to have medical benefits. There are no legal requirements to prove that these products live up to their claims. The name is a combination of "cosmetics" and "pharmaceuticals". "Nutricosmetics" are related dietary supplements or food or beverage products with additives that are marketed as having medical benefits that affect appearance. Cosmetic-containing herbals are topical cosmetic-pharmaceutical hybrids intended to enhance the health and beauty of the skin. Cosmetic-containing herbals improve appearance by delivering essential nutrients to the skin. Several herbal products, such as cosmetic-containing herbals, are available. The present review highlights the use of natural products in cosmetic-containing herbals, as natural products have many curative effects as well as healing effects on skin and hair growth with minimal to no side effects. A brief description is given on such plants, their used parts, active ingredients, and the therapeutic properties associated with them. Mainly, the utilization of phytoconstituents as cosmetic-containing herbals in the care of skin and hair, such as dryness of skin, acne, eczema, inflammation of the skin, aging, hair growth, and dandruff, along with natural ingredients, such as for hair colorant, are explained in detail in the present review.

Therapeutic promise of carotenoids as antioxidants and anti-inflammatory agents in neurodegenerative disorders.

Neurodegenerative disorders (NDs) including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis have various disease-specific causal factors and pathological features. A very common characteristic of NDs is oxidative stress (OS), which takes place due to the elevated generation of reactive oxygen species during the progression of NDs. Furthermore, the pathological condition of NDs including an increased level of protein aggregates can further lead to chronic inflammation because of the microglial activation. Carotenoids (CTs) are naturally occurring pigments that play a significant role in averting brain disorders. More than 750 CTs are present in nature, and they are widely available in plants, microorganisms, and animals. CTs are accountable for the red, yellow, and orange pigments in several animals and plants, and these colors usually indicate various types of CTs. CTs exert various bioactive properties because of its characteristic structure, including anti-inflammatory and antioxidant properties. Due to the protective properties of CTs, levels of CTs in the human body have been markedly linked with the prevention and treatment of multiple diseases including NDs. In this review, we have summarized the relationship between OS, neuroinflammation, and NDs. In addition, we have also particularly focused on the antioxidants and anti-inflammatory properties of CTs in the management of NDs.

Major obstacles to doxorubicin therapy: Cardiotoxicity and drug resistance.

BACKGROUND: Doxorubicin is one of the most commonly prescribed and time-tested anticancer drugs. Although being considered as a first line drug in different types of cancers, the two main obstacles to doxorubicin therapy are drug-induced cardiotoxicity and drug resistance. METHOD: The study utilizes systemic reviews on publications of previous studies obtained from scholarly journal databases including PubMed, Medline, Ebsco Host, Google Scholar, and Cochrane. The study utilizes secondary information obtained from health organizations using filters and keywords to sustain information relevancy. The study utilizes information retrieved from studies captured in the peer-reviewed journals on "doxorubicin-induced cardiotoxicity" and "doxorubicin resistance." DISCUSSION AND RESULTS: The exact mechanisms of cardiotoxicity are not known; various hypotheses are studied. Doxorubicin can lead to free radical generation in various ways. The commonly proposed underlying mechanisms promoting doxorubicin resistance are the expression of multidrug resistance proteins as well as other causes. CONCLUSION: In this review, we have described the major obstacles to doxorubicin therapy, doxorubicin-induced cardiotoxicity as well as the mechanisms of cancer drug resistance and in following the treatment failures.

Modulation of doxorubicin-induced expression of the multidrug resistance gene in breast cancer cells by diltiazem and protection against cardiotoxicity in experimental animals.

BACKGROUND: Doxorubicin (DOX) is one of the most important anticancer agents used in treating breast cancer. However, chronic cardiotoxicity and multidrug resistance limit the chemotherapeutic use of DOX. METHODS: This study aimed to evaluate the capability of calcium channel blocker diltiazem (DIL) to reverse DOX resistance in breast cancer MCF-7 cells and to confer protection against DOX-induced cardiotoxicity in Wistar rats. For this purpose, we explored the effects of DOX on cell cycle phase distribution and expression of ABCB1, FOXO3a, and p53 genes in the presence and absence of DIL (20 µg/ml) and studied the ability of DIL to prevent DOX-induced cardiotoxicity after a single injection of DOX (15 mg/kg) in male Wister rats. RESULTS: We found that compared with DOX alone treatment, DIL + DOX treatment down regulated the ABCB1 gene expression by > fourfold but up regulated the FOXO3a and p53 genes expression by 1.5 fold. DIL treatment conferred protection against DOX-induced cardiotoxicity, as indicated by a decrease in the levels of the cardiac enzyme creatine kinase MB and malondialdehyde and an increase in the total antioxidant capacity and glutathione peroxidase levels. These biochemical results were further confirmed by the histopathological investigation of cardiac cells, which showed normal cardiac cells with central vesicular nuclei and prevention of DOX-induced disruption of normal cardiac architecture in the DIL to DOX group. CONCLUSIONS: Taken together, our results indicate that DIL treatment can reverse the resistance of breast cancer cells to the therapeutic effects of DOX and can protect against DOX-induced cardiotoxicity in rats.