Immunotherapy in Alzheimer's disease: focusing on the efficacy of gantenerumab on amyloid-ß clearance and cognitive decline.

Gantenerumab, a human monoclonal antibody (mAb), has been thought of as a potential agent to treat Alzheimer's disease (AD) by specifically targeting regions of the amyloid-ß (Aß) peptide sequence. Aß protein accumulation in the brain leads to amyloid plaques, causing neuroinflammation, oxidative stress, neuronal damage, and neurotransmitter dysfunction, thereby causing cognitive decline in AD. Gantenerumab involves disrupting Aß aggregation and promoting the breakdown of larger Aß aggregates into smaller fragments, which facilitates the action of Aß-degrading enzymes in the brain, thus slowing down the progression of AD. Moreover, Gantenerumab acts as an opsonin, coating Aß plaques and enhancing their recognition by immune cells, which, combined with its ability to improve the activity of microglia, makes it an intriguing candidate for promoting Aß plaque clearance. Indeed, the multifaceted effects of Gantenerumab, including Aß disaggregation, enhanced immune recognition, and improved microglia activity, may position it as a promising therapeutic approach for AD. Of note, reports suggest that Gantenerumab, albeit its capacity to reduce or eliminate Aß, has not demonstrated effectiveness in reducing cognitive decline. This review, after providing an overview of immunotherapy approaches that target Aß in AD, explores the efficacy of Gantenerumab in reducing Aß levels and cognitive decline.

The role of resveratrol in neurogenesis: a systematic review.

CONTEXT: Resveratrol (RV) is a natural compound found in grapes, wine, berries, and peanuts and has potential health benefits-namely, neurogenesis improvement. Neurogenesis, which is the process through which new neurons or nerve cells are generated in the brain, occurs in the subventricular zone and hippocampus and is influenced by various factors. RV has been shown to increase neural stem cell proliferation and survival, improving cognitive function in hippocampus-dependent tasks. Thus, to provide a convergent and unbiased conclusion of the available evidence on the correlation between the RV and neurogenesis, a systematic review needs to be undertaken meticulously and with appropriate attention. OBJECTIVE: This study aimed to systematically review any potential connection between the RV and neurogenesis in animal models. DATA SOURCES AND EXTRACTION: Based on the particular selection criteria, 8 original animal studies that investigated the relationship between RV and neurogenesis were included. Studies written in English and published in peer-reviewed journals with no restrictions on the starting date of publication on August 17, 2023, were searched in the Google Scholar and PubMed databases. Furthermore, data were extracted and analyzed independently by 2 researchers and then reviewed by a third researcher, and discrepancies were resolved by consensus. This project followed PRISMA reporting standards. DATA ANALYSIS: In the studies analyzed in this review, there is a definite correlation between RV and neurogenesis, meaning that RV intake, irrespective of the mechanisms thereof, can boost neurogenesis in both the subventricular zone and hippocampus. CONCLUSION: This finding, albeit with some limitations, provides a plausible indication of RV's beneficial function in neurogenesis. Indeed, RV intake may result in neurogenesis benefits-namely, cognitive function, mood regulation, stress resilience, and neuroprotection, potentially preventing cognitive decline.

Unraveling the therapeutic efficacy of resveratrol in Alzheimer's disease: an umbrella review of systematic evidence.

CONTEXT: Resveratrol (RV), a natural compound found in grapes, berries, and peanuts, has been extensively studied for its potential in treating Alzheimer's disease (AD). RV has shown promise in inhibiting the formation of beta-amyloid plaques (Aß) and neurofibrillary tangles (NFTs), protecting against neuronal damage and oxidative stress, reducing inflammation, promoting neuroprotection, and improving the function of the blood-brain barrier (BBB). However, conflicting results have been reported, necessitating a comprehensive umbrella review of systematic reviews to provide an unbiased conclusion on the therapeutic effectiveness of RV in AD. OBJECTIVE: The objective of this study was to systematically synthesize and evaluate systematic and meta-analysis reviews investigating the role of RV in AD using data from both human and animal studies. DATA SOURCES AND EXTRACTION: Of the 34 systematic and meta-analysis reviews examining the association between RV and AD that were collected, six were included in this study based on specific selection criteria. To identify pertinent studies, a comprehensive search was conducted in English-language peer-reviewed journals without any restrictions on the publication date until October 15, 2023. The search was carried out across multiple databases, including Embase, MEDLINE (PubMed), Cochrane Library, Web of Science, and Google Scholar, utilizing appropriate terms relevant to the specific research field. The AMSTAR-2 and ROBIS tools were also used to evaluate the quality and risk of bias of the included systematic reviews, respectively. Two researchers independently extracted and analyzed the data, resolving any discrepancies through consensus. Of note, the study adhered to the PRIOR checklist. DATA ANALYSIS: This umbrella review presented robust evidence supporting the positive impacts of RV in AD, irrespective of the specific mechanisms involved. It indeed indicated that all six systematic and meta-analysis reviews unanimously concluded that the consumption of RV can be effective in the treatment of AD. CONCLUSION: RV exhibits promising potential for benefiting individuals with AD through various mechanisms. It has been observed to enhance cognitive function, reduce Aß accumulation, provide neuroprotection, protect the BBB, support mitochondrial function, facilitate synaptic plasticity, stabilize tau proteins, mitigate oxidative stress, and reduce neuroinflammation commonly associated with AD.

Role of the SARS-CoV-2 Virus in Brain Cells.

COVID-19, caused by the SARS-CoV-2 virus, can have neurological effects, including cognitive symptoms like brain fog and memory problems. Research on the neurological effects of COVID-19 is ongoing, and factors such as inflammation, disrupted blood flow, and damage to blood vessels may contribute to cognitive symptoms. Notably, some authors and existing evidence suggest that the SARS-CoV-2 virus can enter the central nervous system through different routes, including the olfactory nerve and the bloodstream. COVID-19 infection has been associated with neurological symptoms such as altered consciousness, headaches, dizziness, and mental disorders. The exact mechanisms and impact on memory formation and brain shrinkage are still being studied. This review will focus on pathways such as the olfactory nerve and blood-brain barrier disruption, and it will then highlight the interactions of the virus with different cell types in the brain, namely neurons, astrocytes, oligodendrocytes, and microglia.

A systematic review of the association between zinc and anxiety.

CONTEXT: The incidence of anxiety, which stems from both intrinsic and extrinsic factors, has been increasing worldwide. Various methods by which it can be treated or prevented have been reported thus far. One of the most popular and effective treatments is supplementation therapy. Zinc, which is an essential nutrient found in various plants, animal foods, and supplements, has been shown to be a potential nutrient in anxiety reduction by acting on γ-aminobutyric acid (GABA), glutamatergic, serotonergic, neurogenesis, and immune systems. It can also influence important receptors, such as GPR39. Thus, zinc has received considerable attention with respect to its potential role as a therapeutic or detrimental factor for anxiety; yet, the available evidence needs to be analyzed systematically to reach a convergent conclusion. OBJECTIVE: The objective was to systematically review any potential connection between adult human anxiety and zinc intake. DATA SOURCES AND EXTRACTION: Nine original human studies, of which 2 assessed the relationship between zinc consumption and anxiety (based on a questionnaire) and 7 assessed the relationship between serum zinc levels and anxiety, were included based on specific selection criteria. Studies that had been written in English and published in peer-reviewed publications with no restrictions on the date of publication were searched in the Google Scholar and PubMed databases. This project was also reported according to the PRISMA guidelines. DATA ANALYSIS: As per the studies analyzed in this review, there was a noticeable relationship between serum zinc levels and anxiety, which means that patients with anxiety have lower levels of zinc in their serum, as compared with healthy individuals. Furthermore, zinc consumption was inversely associated with anxiety. CONCLUSION: The results provide plausible evidence for the positive role of zinc in the treatment of patients afflicted with anxiety, albeit with some limitations.

The role of epigenetics in anxiety disorders.

Anxiety disorders (ADs) are extremely common psychiatric conditions that frequently co-occur with other physical and mental disorders. The pathophysiology of ADs is multifaceted and involves intricate connections among biological elements, environmental stimuli, and psychological mechanisms. Recent discoveries have highlighted the significance of epigenetics in bridging the gap between multiple risk factors that contribute to ADs and expanding our understanding of the pathomechanisms underlying ADs. Epigenetics is the study of how changes in the environment and behavior can have an impact on gene function. Indeed, researchers have found that epigenetic mechanisms can affect how genes are activated or inactivated, as well as whether they are expressed. Such mechanisms may also affect how ADs form and are protected. That is, the bulk of pharmacological trials evaluating epigenetic treatments for the treatment of ADs have used histone deacetylase inhibitors (HDACi), yielding promising outcomes in both preclinical and clinical studies. This review will provide an outline of how epigenetic pathways can be used to treat ADs or lessen their risk. It will also present the findings from preclinical and clinical trials that are currently available on the use of epigenetic drugs to treat ADs.

Dual role of nitric oxide in Alzheimer's disease.

Nitric oxide (NO), an enzymatic product of nitric oxide synthase (NOS), has been associated with a variety of neurological diseases such as Alzheimer's disease (AD). NO has long been thought to contribute to neurotoxic insults caused by neuroinflammation in AD. This perception shifts as more attention is paid to the early stages before cognitive problems manifest. However, it has revealed a compensatory neuroprotective role for NO that protects synapses by increasing neuronal excitability. NO can positively affect neurons by inducing neuroplasticity, neuroprotection, and myelination, as well as having cytolytic activity to reduce inflammation. NO can also induce long-term potentiation (LTP), a process by which synaptic connections among neurons become more potent. Not to mention that such functions give rise to AD protection. Notably, it is unquestionably necessary to conduct more research to clarify NO pathways in neurodegenerative dementias because doing so could help us better understand their pathophysiology and develop more effective treatment options. All these findings bring us to the prevailing notion that NO can be used either as a therapeutic agent in patients afflicted with AD and other memory impairment disorders or as a contributor to the neurotoxic and aggressive factor in AD. In this review, after presenting a general background on AD and NO, various factors that have a pivotal role in both protecting and exacerbating AD and their correlation with NO will be elucidated. Following this, both the neuroprotective and neurotoxic effects of NO on neurons and glial cells among AD cases will be discussed in detail.

Current understanding of epigenetics role in melanoma treatment and resistance.

Melanoma is the most aggressive form of skin cancer resulting from genetic mutations in melanocytes. Several factors have been considered to be involved in melanoma progression, including genetic alteration, processes of damaged DNA repair, and changes in mechanisms of cell growth and proliferation. Epigenetics is the other factor with a crucial role in melanoma development. Epigenetic changes have become novel targets for treating patients suffering from melanoma. These changes can alter the expression of microRNAs and their interaction with target genes, which involves cell growth, differentiation, or even death. Given these circumstances, we conducted the present review to discuss the melanoma risk factors and represent the current knowledge about the factors related to its etiopathogenesis. Moreover, various epigenetic pathways, which are involved in melanoma progression, treatment, and chemo-resistance, as well as employed epigenetic factors as a solution to the problems, will be discussed in detail.

Exosome application in treatment and diagnosis of B-cell disorders: leukemias, multiple sclerosis, and arthritis rheumatoid.

Exosomes, known as a type of extracellular vesicles (EVs), are lipid particles comprising heterogeneous contents such as nucleic acids, proteins, and DNA. These bi-layered particles are naturally released into the extracellular periphery by a variety of cells such as neoplastic cells. Given that exosomes have unique properties, they can be used as vectors and carriers of biological and medicinal particles like drugs for delivering to the desired areas. The proteins and RNAs being encompassed by the circulating exosomes in B-cell malignancies are deemed as the promising sources for diagnostic and prognostic biomarkers, as well as therapeutic agents. Exosomes can also provide a "snapshot" view of the tumor and metastatic landscape at any particular time. Further, clinical research has shown that exosomes are produced by immune cells such as dendritic cells can stimulate the immune system, so these exosomes can be used in antitumor vaccines. Despite the great potential of exosomes in the fields of diagnostic and treatment, further studies are in need for these purposes to reach a convergence notion. This review highlights the applications of exosomes in multiple immune-related diseases, including chronic lymphocytic leukemia, multiple sclerosis, and arthritis rheumatoid, as well as explaining sundry aspects of exosome therapy and the function of exosomes in diagnosing diseases.

Recent Advances in Glioma Cancer Treatment: Conventional and Epigenetic Realms.

Glioblastoma (GBM) is the most typical and aggressive form of primary brain tumor in adults, with a poor prognosis. Successful glioma treatment is hampered by ineffective medication distribution across the blood-brain barrier (BBB) and the emergence of drug resistance. Although a few FDA-approved multimodal treatments are available for glioblastoma, most patients still have poor prognoses. Targeting epigenetic variables, immunotherapy, gene therapy, and different vaccine- and peptide-based treatments are some innovative approaches to improve anti-glioma treatment efficacy. Following the identification of lymphatics in the central nervous system, immunotherapy offers a potential method with the potency to permeate the blood-brain barrier. This review will discuss the rationale, tactics, benefits, and drawbacks of current glioma therapy options in clinical and preclinical investigations.

The role of epigenetic modifications in drug resistance and treatment of breast cancer.

BACKGROUND: Breast cancer is defined as a biological and molecular heterogeneous disorder that originates from breast cells. Genetic predisposition is the most important factor giving rise to this malignancy. The most notable mutations in breast cancer occur in the BRCA1 and BRCA2 genes. Owing to disease heterogeneity, lack of therapeutic target, anti-cancer drug resistance, residual disease, and recurrence, researchers are faced with challenges in developing strategies to treat patients with breast cancer. RESULTS: It has recently been reported that epigenetic processes such as DNA methylation and histone modification, as well as microRNAs (miRNAs), have potently contributed to the pathophysiology, diagnosis, and treatment of breast cancer. These observations have persuaded researchers to move their therapeutic approaches beyond the genetic framework toward the epigenetic concept. CONCLUSION: Herein we discuss the molecular and epigenetic mechanisms underlying breast cancer progression and resistance as well as various aspects of epigenetic-based therapies as monotherapy and combined with immunotherapy.

An overview of current drugs and prophylactic vaccines for coronavirus disease 2019 (COVID-19).

Designing and producing an effective vaccine is the best possible way to reduce the burden and spread of a disease. During the coronavirus disease 2019 (COVID-19) pandemic, many large pharmaceutical and biotechnology companies invested a great deal of time and money in trying to control and combat the disease. In this regard, due to the urgent need, many vaccines are now available earlier than scheduled. Based on their manufacturing technology, the vaccines available for COVID-19 (severe acute respiratory syndrome coronavirus 2 (SAR-CoV2)) infection can be classified into four platforms: RNA vaccines, adenovirus vector vaccines, subunit (protein-based) vaccines, and inactivated virus vaccines. Moreover, various drugs have been deemed to negatively affect the progression of the infection via various actions. However, adaptive variants of the SARS-CoV-2 genome can alter the pathogenic potential of the virus and increase the difficulty of both drug and vaccine development. In this review, along with drugs used in COVID-19 treatment, currently authorized COVID-19 vaccines as well as variants of the virus are described and evaluated, considering all platforms.

Anti-cancer peptide-based therapeutic strategies in solid tumors.

BACKGROUND: Nowadays, conventional medical treatments such as surgery, radiotherapy, and chemotherapy cannot cure all types of cancer. A promising approach to treat solid tumors is the use of tumor-targeting peptides to deliver drugs or active agents selectively. RESULT: Introducing beneficial therapeutic approaches, such as therapeutic peptides and their varied methods of action against tumor cells, can aid researchers in the discovery of novel peptides for cancer treatment. The biomedical applications of therapeutic peptides are highly interesting. These peptides, owing to their high selectivity, specificity, small dimensions, high biocompatibility, and easy modification, provide good opportunities for targeted drug delivery. In recent years, peptides have shown considerable promise as therapeutics or targeting ligands in cancer research and nanotechnology. CONCLUSION:  This study reviews a variety of therapeutic peptides and targeting ligands in cancer therapy. Initially, three types of tumor-homing and cell-penetrating peptides (CPPs) are described, and then their applications in breast, glioma, colorectal, and melanoma cancer research are discussed.

Exosome application in tumorigenesis: diagnosis and treatment of melanoma.

Melanoma is the most aggressive of skin cancer derived from genetic mutations in the melanocytes. Current therapeutic approaches include surgical resection, chemotherapy, photodynamic therapy, immunotherapy, biochemotherapy, and targeted therapy. However, the efficiency of these strategies may be decreased due to the development of diverse resistance mechanisms. Here, it has been proven that therapeutic monoclonal antibodies (mAbs) can improve the efficiency of melanoma therapies and also, cancer vaccines are another approach for the treatment of melanoma that has already improved clinical outcomes in these patients. The use of antibodies and gene vaccines provides a new perspective in melanoma treatment. Since the tumor microenvironment is another important factor for cancer progression and metastasis, in recent times, a mechanism has been identified to provide an opportunity for melanoma cells to communicate with remote cells. This mechanism is involved by a novel molecular structure, named extracellular vesicles (EVs). Depending on the functional status of origin cells, exosomes contain various cargos and different compositions. In this review, we presented recent progress of exosome applications in the treatment of melanoma. Different aspects of exosome therapy and ongoing efforts in this field will be discussed too.

The Role of Cell Organelles in Rheumatoid Arthritis with Focus on Exosomes.

Auto-immune diseases involved at least 25% of the population in wealthy countries. Several factors including genetic, epigenetic, and environmental elements are implicated in development of Rheumatoid Arthritis as an autoimmune disease. Autoantibodies cause synovial inflammation and arthritis, if left untreated or being under continual external stimulation, could result in chronic inflammation, joint injury, and disability. T- and B-cells, signaling molecules, proinflammatory mediators, and synovium-specific targets are among the new therapeutic targets. Exosomes could be employed as therapeutic vectors in the treatment of autoimmune diseases. Herein, the role of cell organelle particularly exosomes in Rheumatoid Arthritis had discussed and some therapeutic applications of exosome highlighted.