Endoplasmic Reticulum as a Therapeutic Target in Cancer: Is there a Role for Flavonoids?

Flavonoids are classified into subclasses of polyphenols, a multipurpose category of natural compounds which comprises secondary metabolites extracted from vascular plants and are plentiful in the human diet. Although the details of flavonoid mechanisms are still not realized correctly, they are generally regarded as antimicrobial, anti-fungal, anti-inflammatory, anti-oxidative; anti-mutagenic; anti-neoplastic; anti-aging; anti-diabetic, cardio-protective, etc. The anti-cancer properties of flavonoids are evident in functions such as prevention of proliferation, metastasis, invasion, inflammation and activation of cell death. Tumors growth and enlargement expose cells to acidosis, hypoxia, and lack of nutrients which result in endoplasmic reticulum (ER) stress; it triggers the unfolded protein response (UPR), which reclaims homeostasis or activates autophagy. Steady stimulation of ER stress can switch autophagy to apoptosis. The connection between ER stress and cancer, in association with UPR, has been explained. The signals provided by UPR can activate or inhibit anti-apoptotic or apoptotic pathways depending on the period and grade of ER stress. In this review, we will peruse the link between flavonoids and their impact on the endoplasmic reticulum in association with cancer therapy.

Neuroprotective effects of flavonoids: endoplasmic reticulum as the target.

The incidence of neurological disorders, particularly age-related neurodegenerative pathologies, exhibits an alarming upward trend, while current pharmacological interventions seldom achieve curative outcomes. Despite their diverse clinical presentations, neurological diseases often share a common pathological thread: the aberrant accumulation of misfolded proteins within the endoplasmic reticulum (ER). This phenomenon, known as ER stress, arises when the cell's intrinsic quality control mechanisms fail to cope with the protein-folding burden. Consequently, misfolded proteins accumulate in the ER lumen, triggering a cascade of cellular stress responses. Recognizing this challenge, researchers have intensified their efforts over the past two decades to explore natural compounds that could potentially slow or even reverse these devastating pathologies. Flavonoids constitute a vast and heterogeneous class of plant polyphenols, with over 10,000 identified from diverse natural sources such as wines, vegetables, medicinal plants, and organic products. Flavonoids are generally divided into six different subclasses: anthocyanidins, flavanones, flavones, flavonols, isoflavones, and flavonols. The diverse family of flavonoids, featuring a common phenolic ring backbone adorned with varying hydroxyl groups and additional modifications, exerts its antioxidant activity by inhibiting the formation of ROS, as evidenced by research. Also, studies suggest that polyphenols such as flavonoids can regulate ER stress through apoptosis and autophagy. By understanding these mechanisms, we can unlock the potential of flavonoids as novel therapeutic agents for neurodegenerative disorders. Therefore, this review critically examines the literature exploring the modulatory effects of flavonoids on various steps of the ER stress in neurological disorders.

The effects of hydroxychloroquine on pregnancy outcomes in infertile women: a systematic review and meta-analysis.

A promising strategy for controlling repeated implantation failure (RIF) may be the use of hydroxychloroquine (HCQ). To the best of our knowledge, no systematic review has been conducted on the effects of hydroxychloroquine on pregnancy outcomes. A systematic research of the following electronic databases was conducted: Cochrane, EMBASE-Ovid, PubMed, Web of Science, and Scopus from inception to December 2021, using the following keywords [hydroxychloroquine] AND [infertility]. Fertilization and rate of live birth were significantly higher in the HCQ+ prednisone (PDN) group than in the PDN alone group. However, the abortion rate was not different between the two groups. The meta-analysis of two studies revealed no statistical significance between the PDN group and HCQ+PDN group regarding clinical pregnancy rate (OR=.14 [95%CI: 0.4-4.370]; heterogeneity; P=0.13; I2=54%; random effect model) and implantation rate (OR=1.99 [95%CI: 0.94-4.2]; heterogeneity; P=0.37; I2=0%; fixed-effect model). While HCQ may help improve fertilization and live birth rates, adding it to prednisone did not improve overall pregnancy outcomes. This systematic review should be used with caution due to the small size, study design, and difference in the studies' population.

Venous thromboembolism in viral diseases: A comprehensive literature review.

Venous thromboembolism (VTE) is known to be a common respiratory and/or cardiovascular complication in hospitalized patients with viral infections. Numerous studies have proven human immunodeficiency virus infection to be a prothrombotic condition. An elevated VTE risk has been observed in critically ill H1N1 influenza patients. VTE risk is remarkably higher in patients infected with the Hepatitis C virus in contrast to uninfected subjects. The elevation of D-dimer levels supported the association between Chikungunya and the Zika virus and the rise of clinical VTE risk. Varicella-zoster virus is a risk factor for both cellulitis and the consequent invasive bacterial disease which may take part in thrombotic initiation. Eventually, hospitalized patients infected with the coronavirus disease of 2019 (COVID-19), the cause of the ongoing worldwide pandemic, could mainly suffer from an anomalous risk of coagulation activation with enhanced venous thrombosis events and poor quality clinical course. Although the risk of VTE in nonhospitalized COVID-19 patients is not known yet, there are a large number of guidelines and studies on thromboprophylaxis administration for COVID-19 cases. This study aims to take a detailed look at the effect of viral diseases on VTE, the epidemiology of VTE in viral diseases, and the diagnosis and treatment of VTE.

Neuroprotective Potential of Aromatic Herbs: Rosemary, Sage, and Lavender.

Hundreds of millions of people around the world suffer from neurological disorders or have experienced them intermittently, which has significantly reduced their quality of life. The common treatments for neurological disorders are relatively expensive and may lead to a wide variety of side effects including sleep attacks, gastrointestinal side effects, blood pressure changes, etc. On the other hand, several herbal medications have attracted colossal popularity worldwide in the recent years due to their availability, affordable prices, and few side effects. Aromatic plants, sage (Salvia officinalis), lavender (Lavandula angustifolia), and rosemary (Salvia Rosmarinus) have already shown anxiolytics, anti-inflammatory, antioxidant, and neuroprotective effects. They have also shown potential in treating common neurological disorders, including Alzheimer's disease, Parkinson's disease, migraine, and cognitive disorders. This review summarizes the data on the neuroprotective potential of aromatic herbs, sage, lavender, and rosemary.

Pharmacotherapeutic potential of Vitis vinifera(grape) in age-related neurological diseases / Potencial farmacoterapéutico de Vitis vinifera(uva) en enfermedades neurológicas asociadas a la edad

Age-related neurological disorders (ANDs), including neurodegenerative diseases, are complex illnesses with an increasing risk with advancing years. The central nervous system's neuropathological conditions, including oxidative stress, neuroinflammation, and protein misfolding, are what define ANDs. Due to the rise in age-dependent prevalence, efforts have been made to combat ANDs. Vitis viniferahas a long history of usageto treat a variety of illness symptoms. Because multiple ligand sites may be targeted, Vitis viniferacomponents can be employed to treat ANDs. This is demonstrated by the link between the structure and action of these compounds. This review demonstrates that Vitis viniferaand its constituents, including flavonoids, phenolic compounds, stilbenoidsandaromatic acids, are effective at reducing the neurological symptoms and pathological conditions of ANDs. This is done by acting as an antioxidant and anti-inflammatory. The active Vitis vinifera ingredients have therapeutic effects on ANDs, as this review explains.

Las enfermedades neurológicas asociadas a la edad (AND, por su sigla en inglés) incluyendo las enfermedades neurodegenerativas, son enfermedades complejas con un riesgo creciente con la edad. Las condiciones neuropatológicas del sistema nervioso central, que incluyen el estrés oxidativo, la neuro inflamación, y el plegado erróneo de proteínas, son lo que define las AND. Debido al aumento en la prevalencia dependiente de la edad, se han hecho esfuerzos para combatir las AND. Vitis vinifera tiene una larga historia de uso para el tratamiento de síntomas. Puesto que puede hacer objetivo a muchos sitios ligando, los componentes de Vitis viniferase pueden utilizar para tratar AND. Esto se demuestra por el vínculo entre la estructura y la acción de estos compuestos. Esta revisión demuestra que la Vitis viniferay sus constituyentes, incluídos los flavonoides, componentes fenólicos, estilbenoides, y ácidos aromáticos, son efectivos para reducir los síntomas neurológicos y las condiciones patológicas de AND. Esto se produce por su acción como antioxidante y antiinflamatorio. Los ingredientes activos de Vitis vinifera tienen efectos terapéuticos en AND, y esta revisión lo explica.