From Gut Microbiomes to Infectious Pathogens: Neurological Disease Game Changers.

Gut microbiota and infectious diseases affect neurological disorders, brain development, and function. Compounds generated in the gastrointestinal system by gut microbiota and infectious pathogens may mediate gut-brain interactions, which may circulate throughout the body and spread to numerous organs, including the brain. Studies shown that gut bacteria and disease-causing organisms may pass molecular signals to the brain, affecting neurological function, neurodevelopment, and neurodegenerative diseases. This article discusses microorganism-producing metabolites with neuromodulator activity, signaling routes from microbial flora to the brain, and the potential direct effects of gut bacteria and infectious pathogens on brain cells. The review also considered the neurological aspects of infectious diseases. The infectious diseases affecting neurological functions and the disease modifications have been discussed thoroughly. Recent discoveries and unique insights in this perspective need further validation. Research on the complex molecular interactions between gut bacteria, infectious pathogens, and the CNS provides valuable insights into the pathogenesis of neurodegenerative, behavioral, and psychiatric illnesses. This study may provide insights into advanced drug discovery processes for neurological disorders by considering the influence of microbial communities inside the human body.

Untangling breast cancer: Trailing towards nanoformulations-based drug development.

All over the world, cancer death and prevalence are increasing. Breast cancer (BC) is the major cause of cancer mortality (15%) which makes it the most common cancer in women. BC is defined as the furious progression and quick division of breast cells. Novel nanotechnology-based approaches helped in improving survival rate, metastatic BC is still facing obstacles to treat with an expected overall 23% survival rate. This paper represents epidemiology, classification (non-invasive, invasive and metastatic), risk factors (genetic and non-genetic) and treatment challenges of breast cancer in brief. This review paper focus on the importance of nanotechnology-based nanoformulations for treatment of BC. This review aims to deliver elementary insight and understanding of the novel nanoformulations in BC treatment and to explain to the readers for enduring designing novel nanomedicine. Later, we elaborate on several types of nanoformulations used in tumor therapeutics such as liposomes, dendrimers, polymeric nanomaterials and many others. Potential research opportunities for clinical application and current challenges related to nanoformulations utility for the treatment of BC are also highlighted in this review. The role of artificial intelligence is elaborated in detail. We also confer the existing challenges and perspectives of nanoformulations in effective tumor management, with emphasis on the various patented nanoformulations approved or progression of clinical trials retrieved from various search engines.

Guaiazulene and related compounds: A review of current perspective on biomedical applications.

BACKGROUND: Thousands of people worldwide pass away yearly due to neurological disorders, cardiovascular illnesses, cancer, metabolic disorders, and microbial infections. Additionally, a sizable population has also been impacted by hepatotoxicity, ulcers, gastroesophageal reflux disease, and breast fissure. These ailments are likewise steadily increasing along with the increase in life expectancy. Finding innovative therapies to cure and consequently lessen the impact of these ailments is, therefore, a global concern. METHODS AND MATERIALS: All provided literature on Guaiazulene (GA) and its related compounds were searched using various electronic databases such as PubMed, Google Scholar, Web of Science, Elsevier, Springer, ACS, CNKI, and books via the keywords Guaiazulene, Matricaria chamomilla, GA-related compounds, and Guaiazulene analogous. RESULTS: The FDA has approved the bicyclic sesquiterpene GA, commonly referred to as azulon or 1,4-dimethyl-7-isopropylazulene, as a component in cosmetic colorants. The pleiotropic health advantages of GA and related substances, especially their antioxidant and anti-inflammatory effects, attracted a lot of research. Numerous studies have found that GA can help to manage various conditions, including bacterial infections, tumors, immunomodulation, expectorants, diuretics, diaphoresis, ulcers, dermatitis, proliferation, and gastritis. These conditions all involve lipid peroxidation and inflammatory response. In this review, we have covered the biomedical applications of GA. Moreover, we also emphasize the therapeutic potential of guaiazulene derivatives in pre-clinical and clinical settings, along with their underlying mechanism(s). CONCLUSION: GA and its related compounds exhibit therapeutic potential in several diseases. Still, it is necessary to investigate their potential in animal models for various other ailments and establish their safety profile. They might be a good candidate to advance to clinical trials.

Influence of toll-like receptor-4 antagonist on bacterial load of asthma in Swiss albino mice: targeting TLR4/MD2 complex pathway.

Air pollution and environmental issues significantly impact life, resulting in the emergence and exacerbation of allergic asthma and other chronic respiratory infections. The main objective of this study is to suppress allergic asthma by TAK-242 from lipopolysaccharide-induced airway inflammation primarily stimulating toll-like receptor-4, and also to determine the potential mechanism of asthma eradication. The TAK-242 anti-allergic action was assured through the ovalbumin murine model of asthma via bronchial hyperresponsiveness and inflammation of the respiration tract in a pre-existing allergic inflammation paradigm. Swiss albino mice were sensitized and then challenged by ovalbumin and lipopolysaccharide for 5 days straight. TAK-242 reaction was assessed by inflammatory cytokines, and inflammatory cell count was determined from blood serum and bronchoalveolar lavage fluid, as well as group-wise regular weight assessments. After ovalbumin, lipopolysaccharide infusion, toll-like receptor-4 agonists caused a substantial increase in airway hyperresponsiveness, specific cellular inflammation, histological alterations, and immune mediator synthesis, as well as dose-related body-weight variations. A decrease in lipopolysaccharide-induced leukocyte count and Th1/Th17 related cytokines, TNF-α, and IL-6 expression through the ELISA study was particularly noticeable. Finally in treated groups, TAK-242, a TLR4/MD2 complex inhibitor, reduced airway inflammation and histopathological changes, cytokine expression, and body-weight management. TAK-242 has been found in an ovalbumin allergic asthma model to be a potential inhibitor of lipopolysaccharide-induced respiratory infection.

Effect of TLR3/dsRNA complex inhibitor on Poly(I:C)-induced airway inflammation in Swiss albino mice.

Rhinovirus infection frequently causes COPD and asthma exacerbations. Impaired anti-viral signaling and reduced viral clearance have both been seen in sick bronchial epithelium, potentially increasing exacerbations. Polyinosinic:polycytidylic acid (Poly(I:C)), a Toll-like receptor-3 (TLR3) ligand, has been shown to cause a viral exacerbation of severe asthma by detecting double-stranded RNA (dsRNA). The purpose of this work was to determine the effect of a TLR3/dsRNA complex inhibitor-Calbiochem drug in the prevention of Poly(I:C)-induced airway inflammation following TLR3 activation and to uncover a potential pathway for the cure of asthma through TLR3 inhibition. Mice were sensitized with Poly(I:C) as an asthma model before being challenged by PBS and ovalbumin (OVA) chemicals. The mice were administered a TLR3/dsRNA complex inhibitor. Throughout the trial, the mice's body weight was measured after each dosage. Biochemical methods are used to analyze the protein as well as enzyme composition in airway tissues. BALF specimens are stained using Giemsa to identify inflammatory cells and lung histopathology to determine morphological abnormalities in lung tissues. By using the ELISA approach, cytokine levels such as TNF-α, IL-13, IL-6, IL-5, and IgE antibody expression in lung tissue and blood serum were assessed. TLR3/dsRNA complex inhibitor drug significantly lowered the number of cells in BALF and also on Giemsa staining slides. It also downregulated the level of TNF-α and IL-6 in contrast to OVA and Poly(I:C) administered in animals. A TLR3/dsRNA complex inhibitor decreased the fraction of oxidative stress markers (MDA, GSH, GPx, and CAT) in lung tissues while keeping the mice's body weight constant during the treatment period. By decreasing alveoli, bronchial narrowing, smooth muscle hypertrophy, and granulocyte levels, the TLR3/dsRNA complex blocker significantly reduced the histopathological damage caused by OVA and Poly(I:C) compounds. In an animal model utilizing ovalbumin, TLR3/dsRNA complex inhibitors similarly reduced the bronchial damage produced by Poly(I:C). A novel TLR3/dsRNA complex inhibitor is expected to be employed in clinical studies since it suppresses airway inflammation without inducing antiviral approach resistance.

Multifunctional Patented Nanotherapeutics for Cancer Intervention: 2010- Onwards.

Even today, cancer is one of the prominent leading causes of death worldwide. However, there are a couple of treatment options available for management, but the adverse effects are more prominent as compared to therapeutic effects. Therefore, there is a need to design some midway that may help to bypass the negative effects or lower their severity. Nanotechnology has addressed many issues, still many miles are needed to cover before reaching the center stage. The developed nanoformulations can target distant organs owing to their multifunctionality and targeting potential. Stimuli-responsive nanomedicine is one of the most exploited formulations. They can encapsulate and release the drugs for a higher period. However, they release a burst mechanism. The other nanoformulations contain dendrimers, micelles, and lipid-based nano-formulations that have been developed and evaluated for their efficacy in cancer treatment. This review paper highlights some significant patents granted/applied in various patent offices around the globe to treat cancer using the nanotechnology. The Google Patent, United States Patent and Trademark Office (USPTO), Escapenet, and many others were used as the search engine for patent search, and data were collected and analyzed. They used these patented technologies for diagnostic and treatment options, enhancing the absorption, distribution, metabolism, and excretion (ADME) profile of therapeutic molecules.

Exploring the Role of Self-Nanoemulsifying Systems in Drug Delivery: Challenges, Issues, Applications and Recent Advances.

Nanotechnology has attracted researchers around the globe owing to the small size and targeting properties of the drug delivery vectors. The interest in self-nanoemulsifying drug delivery systems (SNEDDS) has shown an exponential increase from the formulator's point of view. SNEDDS have shown wide applicability in terms of controlled and targeted delivery of various types of drugs. They chemically consist of oil, surfactants and co-surfactants that decrease the emulsion particle size to the range of <100 nm. However, stability issues such as drug precipitation during storage, incompatibility of ingredients in shell, decrease their application for the long run and these issues have been highlighted in this paper. The current review throws limelight on the biological aspects and process parameters. In addition, the process of absorption from GI is also discussed in detail. SNEDDS have been utilized as a treatment option for various diseases like cancer, diabetes, and ocular and pulmonary diseases. Along with this, the authors highlight the advances involving in vivo and in vitro lipolysis studies on SNEDDS, also highlighting recent innovations in this field, such as novel combinations of drug-free solid SNEDDS + solid dispersions, lipid-modified chitosan containing mucoadhesive SNEDDS, pHsensitive SNEDDS and several others.

Potential Therapeutic Approach of Melatonin against Omicron and Some Other Variants of SARS-CoV-2.

The Omicron variant (B.529) of COVID-19 caused disease outbreaks worldwide because of its contagious and diverse mutations. To reduce these outbreaks, therapeutic drugs and adjuvant vaccines have been applied for the treatment of the disease. However, these drugs have not shown high efficacy in reducing COVID-19 severity, and even antiviral drugs have not shown to be effective. Researchers thus continue to search for an effective adjuvant therapy with a combination of drugs or vaccines to treat COVID-19 disease. We were motivated to consider melatonin as a defensive agent against SARS-CoV-2 because of its various unique properties. Over 200 scientific publications have shown the significant effects of melatonin in treating diseases, with strong antioxidant, anti-inflammatory, and immunomodulatory effects. Melatonin has a high safety profile, but it needs further clinical trials and experiments for use as a therapeutic agent against the Omicron variant of COVID-19. It might immediately be able to prevent the development of severe symptoms caused by the coronavirus and can reduce the severity of the infection by improving immunity.

Heterocyclic Compounds as Dipeptidyl Peptidase-IV Inhibitors with Special Emphasis on Oxadiazoles as Potent Anti-Diabetic Agents.

Dipeptidyl peptidase-IV (DPP-IV) inhibitors, often known as gliptins, have been used to treat type 2 diabetes mellitus (T2DM). They may be combined with other medications as an additional treatment or used alone as a monotherapy. In addition to insulin, sulfonylureas, thiazolidinediones, and metformin, these molecules appear as possible therapeutic options. Oxadiazole rings have been employed in numerous different ways during drug development efforts. It has been shown that including them in the pharmacophore increases the amount of ligand that may be bound. The exceptional hydrogen bond acceptor properties of oxadiazoles and the distinct hydrocarbon bonding potential of their regioisomers have been established. Beside their anti-diabetic effects, oxadiazoles display a wide range of pharmacological properties. In this study, we made the assumption that molecules containing oxadiazole rings may afford a different approach to the treatment of diabetes, not only for controlling glycemic levels but also for preventing atherosclerosis progression and other complications associated with diabetes. It was observed that oxadiazole fusion with benzothiazole, 5-(2,5,2-trifluoroethoxy) phenyl, ß-homophenylalanine, 2-methyl-2-{5-(4-chlorophenyl), diamine-bridged bis-coumarinyl, 5-aryl-2-(6'-nitrobenzofuran-2'-yl), nitrobenzofuran, and/or oxindole leads to potential anti-diabetic activity.

Involvement of Resveratrol against Brain Cancer: A Combination Strategy with a Pharmaceutical Approach.

A brain tumor (BT) is a condition in which there is growth or uncontrolled development of the brain cells, which usually goes unrecognized or is diagnosed at the later stages. Since the mechanism behind BT is not clear, and the various physiological conditions are difficult to diagnose, the success rate of BT is not very high. This is the central issue faced during drug development and clinical trials with almost all types of neurodegenerative disorders. In the first part of this review, we focus on the concept of brain tumors, their barriers, and the types of delivery possible to target the brain cells. Although various treatment methods are available, they all have side effects or toxic effects. Hence, in the second part, a correlation was made between the use of resveratrol, a potent antioxidant, and its advantages for brain diseases. The relationship between brain disease and the blood-brain barrier, multi-drug resistance, and the use of nanomedicine for treating brain disorders is also mentioned. In short, a hypothetical concept is given with a background investigation into the use of combination therapy with resveratrol as an active ingredient, the possible drug delivery, and its formulation-based approach.

Phytochemical Profiling and Bio-Potentiality of Genus Scutellaria: Biomedical Approach.

Scutellaria (Lamiaceae) comprises over 360 species. Based on its morphological structure of calyx, also known as Skullcap, it is herbaceous by habit and cosmopolitan by habitat. The species of Scutellaria are widely used in local communities as a natural remedy. The genus contributed over three hundred bioactive compounds mainly represented by flavonoids and phenols, chemical ingredients which serve as potential candidates for the therapy of various biological activities. Thus, the current review is an attempt to highlight the biological significance and its correlation to various isolated bioactive ingredients including flavonoids, terpenoids, phenols, alkaloids, and steroids. However, flavonoids were the dominant group observed. The findings of the Scutellaria reveal that due to its affluent basis of numerous chemical ingredients it has a diverse range of pharmacological potentials, such as antimicrobial, antioxidant, antifeedant, enzyme inhibition, anti-inflammatory, and analgesic significance. Currently, various bioactive ingredients have been investigated for various biological activities from the genus Scutellaria in vitro and in vivo. Furthermore, these data help us to highlight its biomedical application and to isolate the responsible compounds to produce innovative medications as an alternative to synthetic drugs.

A Prospective Viewpoint on Neurological Diseases and Their Biomarkers.

Neurodegenerative diseases (NDDs) are disorders that affect both the central and peripheral nervous systems. To name a few causes, NDDs can be caused by ischemia, oxidative and endoplasmic reticulum (ER) cell stress, inflammation, abnormal protein deposition in neural tissue, autoimmune-mediated neuron loss, and viral or prion infections. These conditions include Alzheimer's disease (AD), Lewy body dementia (LBD), and Parkinson's disease (PD). The formation of ß-sheet-rich aggregates of intra- or extracellular proteins in the CNS hallmarks all neurodegenerative proteinopathies. In systemic lupus erythematosus (SLE), numerous organs, including the central nervous system (CNS), are affected. However, the inflammatory process is linked to several neurodegenerative pathways that are linked to depression because of NDDs. Pro-inflammatory signals activated by aging may increase vulnerability to neuropsychiatric disorders. Viruses may increase macrophages and CCR5+ T cells within the CNS during dementia formation and progression. Unlike medical symptoms, which are just signs of a patient's health as expressed and perceived, biomarkers are reproducible and quantitative. Therefore, this current review will highlight and summarize the neurological disorders and their biomarkers.

Multidrug Resistance of Cancer Cells and the Vital Role of P-Glycoprotein.

P-glycoprotein (P-gp) is a major factor in the multidrug resistance phenotype in cancer cells. P-gp is a protein that regulates the ATP-dependent efflux of a wide range of anticancer medicines and confers resistance. Due to its wide specificity, several attempts have been made to block the action of P-gp to restore the efficacy of anticancer drugs. The major goal has been to create molecules that either compete with anticancer medicines for transport or function as a direct P-gp inhibitor. Despite significant in vitro success, there are presently no drugs available in the clinic that can "block" P-gp-mediated resistance. Toxicity, unfavourable pharmacological interactions, and a variety of pharmacokinetic difficulties might all be the reason for the failure. On the other hand, P-gp has a significant effect in the body. It protects the vital organs from the entry of foreign bodies and other toxic chemicals. Hence, the inhibitors of P-gp should not hinder its action in the normal cells. To develop an effective inhibitor of P-gp, thorough background knowledge is needed in this field. The main aim of this review article was to set forth the merits and demerits of the action of P-gp on cancer cells as well as on normal cells. The influence of P-gp on cancer drug delivery and the contribution of P-gp to activating drug resistance were also mentioned.

COVID-19 diagnostic methods in developing countries.

COVID-19 has become one of the few leading causes of death and has evolved into a pandemic that disrupts everyone's routine, and balanced way of life worldwide, and will continue to do so. To bring an end to this pandemic, scientists had put their all effort into discovering the vaccine for SARS-CoV-2 infection. For their dedication, now, we have a handful of COVID-19 vaccines. Worldwide, millions of people are at risk due to the current pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Despite the lack of clinically authorized antiviral medications and vaccines for COVID-19, clinical trials of many recognized antiviral agents, their combination, and vaccine development in patients with confirmed COVID-19 are still ongoing. This discovery gave us a chance to get immune to this disease worldwide and end the pandemic. However, the unexpected capacity of mutation of the SARS-CoV-2 virus makes it difficult, like the recent SAS-CoV-2 Omicron variant. Therefore, there is a great necessity to spread the vaccination programs and prevent the spread of this dreadful epidemic by identifying and isolating afflicted patients. Furthermore, several COVID-19 tests are thought to be expensive, time-consuming, and require the use of adequately qualified persons to be carried out efficiently. In addition, we also conversed about how the various COVID-19 testing methods can be implemented for the first time in a developing country and their cost-effectiveness, accuracy, human resources requirements, and laboratory facilities.

Nanomedicine-Based Delivery Strategies for Breast Cancer Treatment and Management.

Breast cancer is one of the most common types of cancer among women globally. It is caused by mutations in the estrogen/progesterone receptors and conventional treatment methods are commonly utilized. About 70-80 percent of individuals with the early-stage non-metastatic disease may be cured. Conventional treatment is far less than the optimal ratio, as demonstrated through the high mortality rate of women with this cancer. However, conventional treatment methods like surgery, radiotherapy, and chemotherapy are not as effective as expected and lead to concerns about low bioavailability, low cellular uptake, emerging resistance, and adverse toxicities. A nanomedicine-based approach is a promising alternative for breast cancer treatment. The present era is witnessing rapid advancements in nanomedicine as a platform for investigating novel therapeutic applications and modern intelligent healthcare management strategies. This paper focuses on nanomedicine-based therapeutic interventions that are becoming more widely accepted for improving treatment effectiveness and reducing undesired side effects in breast cancer patients. By evaluating the state-of-the-art tools and taking the challenges involved into consideration, various aspects of the proposed nano-enabled therapeutic approaches have been discussed in this review.

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.

Potential innovation against Alzheimer's disorder: a tricomponent combination of natural antioxidants (vitamin E, quercetin, and basil oil) and the development of its intranasal delivery.

Alzheimer's disorder (AD) is very difficult to manage and treat. The complexity of the brain, the blood-brain barrier influencing a multitude of parameters/biomarkers, as well as numerous other factors involved often contribute to the decline in the chances of treatment success. Development of the new drug moiety also takes time, being necessary to consider both its toxicity and related issues. As a strategic plan, a combined strategy is being developed and considered to address AD pathology using several approaches. A combination of vitamin E, quercetin, and basil oil in a nano-based formulation is designed to be administered nasally. The antioxidant present in these natural-based products helps to treat and alleviate AD if a synergistic approach is considered. The three active substances mentioned above are well known for the treatment of neurodegenerative disorders. The nanoformulation helps the co-delivery of the drug moiety to the brain through the intranasal route. In this review, a correlation and use of vitamin E, quercetin, and basil oil in a nano-based formulation is described as an effective way to treat AD. The intranasal administration of drugs is a promising approach for the treatment of neurodegenerative and mental disorders, as this route is non-invasive, enhances the bioavailability, allows a drug dose reduction, bypasses the blood-brain barrier, and reduces the systemic undesired effect. The use of natural products is generally considered to be just as safe; therefore, by using this combined approach, the level of toxicity can be minimized.

Multifaceted Effects of Intermittent Fasting on the Treatment and Prevention of Diabetes, Cancer, Obesity or Other Chronic Diseases.

BACKGROUND: Obesity and diabetes are global epidemics resulting in a range of comorbidities. Both have been linked to an increased risk of hormonal imbalance, cancer, and other significant disorders, which are a concerning trend for cancer rates in the backdrop of rising obesity and diabetes rates worldwide. Around 1 in 10 persons in the United States and Canada have serious illnesses correlated to type 2 diabetes and early death. It is believed that the US economy alone spends $245 billion annually due to this health burden. Lifestyle modification with intermittent fasting protocol and proper diet helps lower blood glucose level, maintain the body mass index, and reduce inflammation, which is the main cause of all chronic diseases. METHODS: We searched case series and clinical trials on type 2 diabetes, insulin resistance, cancer, thyroid, cardiovascular disease, or other inflammatory diseases in response to intermittent fasting in the PubMed, MEDLINE, and Google Scholar databases. OBJECTIVE: In this review, we have focused on intermittent fasting-based approaches that are becoming more widely accepted for improving health and reducing unwanted effects in patients with type 2 diabetes, cancer, cardiovascular disease, neurodegenerative disease, obesity, thyroid, and hormonal imbalance; it is also contemplated whether intermittent fasting can be considered as a non-medicinal therapeutic option for persons suffering from chronic diseases. CONCLUSION: Intermittent fasting successfully reversed diabetes, thyroid, and high blood pressure, elevated lipid levels, and maintained the body mass index; also, studies have shown that it has been instructed to be followed for the treatment and prevention of cancer and neurodegenerative diseases.

The Multifaceted Role of Curcumin in Advanced Nanocurcumin Form in the Treatment and Management of Chronic Disorders.

Curcumin is the primary polyphenol in turmeric's curcuminoid class. It has a wide range of therapeutic applications, such as anti-inflammatory, antioxidant, antidiabetic, hepatoprotective, antibacterial, and anticancer effects against various cancers, but has poor solubility and low bioavailability. Objective: To improve curcumin's bioavailability, plasma concentration, and cellular permeability processes. The nanocurcumin approach over curcumin has been proven appropriate for encapsulating or loading curcumin (nanocurcumin) to increase its therapeutic potential. Conclusion: Though incorporating curcumin into nanocurcumin form may be a viable method for overcoming its intrinsic limitations, and there are reasonable concerns regarding its toxicological safety once it enters biological pathways. This review article mainly highlights the therapeutic benefits of nanocurcumin over curcumin.