Molecular exploration of hidden pleiotropic activities of azoles on dermatophytes in human tinea corporis infection.

Dermatophyte infections are widespread worldwide and are the most prevalent cause of fungal infection of the skin, hair, and nails. Tinea corporis is most commonly caused by dermatophytes belonging to three genera: Trichophyton , Microsporum , and Epidermophyton. The disease may be acquired through person-to-person transmission, typically by direct communication with an infected individual. Since dermatophytes causing tinea corporis infection are restricted to superficial keratinized tissue, topical treatments are most effective in patients with naïve tinea corporis unless the disease is widespread. Dermatophyte adherence to a keratinized structure is an essential step in dermatophytosis pathogenesis, whereby proteolytic enzyme activity is converted into a particular keratolytic activity that encourages the dermatophyte to use keratin as the sole source of carbon. Despite increasing dermatophytosis worldwide, particularly in the tropics, this research has often been neglected, appears to predominate globally, and presents practitioners with a therapeutic challenge. However, experts supported the use of allylamines in the pleiotropic molecular exploration of azoles, including reactive oxygen species (ROS) inducer, anti-inflammatory, antibacterial, and wide-spectrum antimycotic effects. Therefore, the current review aims to update and reform this essential subject and illustrate the recent advancement of the hidden pleiotropic activity of azoles at the molecular level on dermatophytes in human tinea corporis infection.

Exploring Marine as a Rich Source of Bioactive Peptides: Challenges and Opportunities from Marine Pharmacology.

This review highlights the underexplored potential and promises of marine bioactive peptides (MBPs) with unique structural, physicochemical, and biological activities to fight against the current and future human pathologies. A particular focus is given to the marine environment as a significant source to obtain or extract high-value MBPs from touched/untouched sources. For instance, marine microorganisms, including microalgae, bacteria, fungi, and marine polysaccharides, are considered prolific sources of amino acids at large, and peptides/polypeptides in particular, with fundamental structural sequence and functional entities of a carboxyl group, amine, hydrogen, and a variety of R groups. Thus, MBPs with tunable features, both structural and functional entities, along with bioactive traits of clinical and therapeutic value, are of ultimate interest to reinforce biomedical settings in the 21st century. On the other front, as the largest biome globally, the marine biome is the so-called "epitome of untouched or underexploited natural resources" and a considerable source with significant potentialities. Therefore, considering their biological and biomedical importance, researchers around the globe are redirecting and/or regaining their interests in valorizing the marine biome-based MBPs. This review focuses on the widespread bioactivities of MBPs, FDA-approved MBPs in the market, sustainable development goals (SDGs), and legislation to valorize marine biome to underlying the impact role of bioactive elements with the related pathways. Finally, a detailed overview of current challenges, conclusions, and future perspectives is also given to satisfy the stimulating demands of the pharmaceutical sector of the modern world.

Current update on psyllium and alginate incorporate for interpenetrating polymer network (IPN) and their biomedical applications.

Natural polysaccharides and their designed structures are extremely valuable due to their intrinsic pharmacological properties and are also used as pharmaceutical aids. These naturally occurring polysaccharides (e.g., psyllium and alginate) are gaining popularity for their use in the preparation of interpenetrating polymer network (IPN) materials with improved swelling ability, biodegradability, stability, non-cytotoxic, biocompatibility, and cost-effectiveness. IPN is prepared sequentially or simultaneously by microwave irradiation, casting evaporation, emulsification cross-linking, miniemulsion/inverse miniemulsion technique, and radiation polymerization methods. In addition, the prepared IPNs have has been extensively characterized using various analytical and imaging techniques before sustainable deployment for multiple applications. Regardless of these multi-characteristic attributes, the current literature lacks a detailed overview of the biomedical aspects of psyllium, alginate, and their engineered IPN structures. Herein, we highlight the unique synthesis, structural, and biomedical considerations of psyllium, alginate, and engineered IPN structures. In this review, a wide range of biomedical applications, such as role as a drug carrier for sustain delivery, wound dressing, tissue engineering, and related miscellaneous application of psyllium, alginate, and their IPN structures described with appropriate examples. Further research will be carried out for the development of IPN using psyllium and alginate, which will be a smart and active carrier for drugs used in the treatment of life-threatening diseases due to their inherent pharmacological potential such as hypoglycemic, immunomodulatory, antineoplastic, and antimicrobial.

Synergistic role of bacterial consortium to biodegrade toxic dyes containing wastewater and its simultaneous reuse as an added value.

The current environmental research has fascinated the sustainable exploitation of mix bacterial consortium to biodegrade the environmentally-related toxic compounds, including hazardous synthetic dyes. Based on the existing literature evidence, textile and other industrial waste effluents pollute the natural water bodies. Textile effluent contains synthetic dyes which are liberated in the environment without proper treatment. The presence of toxic dyes added to the textile effluents undoubtedly affects the flora and fauna as that untreated water is used for irrigation by local farmers. Many conventional and biological methods are in action for the treatment of wastewater. Physical and chemical processes are expensive as compared to microbial treatments. The use of microbial consortia generates efficient results. Wastewater is a valuable resource, however, up to 80% of wastewater is released to different water matrices. This discernment needs to change for a better tomorrow. In this context, herein, we present a robust microbial-assisted treatment and simultaneously reuse of the treated wastewater as an added value to induce plant growth. Thus, the microbial approach for textile waste treatment release by-product after degradation should be non-toxic for the environment. In the present study, the toxicity of synthetic textile dye named Reactive Red 120, Reactive Orange 122, Reactive Yellow 160, and Reactive Blue 19 was investigated using a bioassay method with plant species namely Sorghum bicolor. Plate and Pot experiment was conducted with respect to untreated Azo dyes, degraded metabolites obtained from single bacteria, and consortium. Efficient Seed germination (89%), shoot length (12.4 cm), root length (15.6 cm) of the plants were observed for bacterial consortium degraded metabolites exposed seeds after comparing with the control. The degraded metabolite also increases protein (45.56 mg/g) and sugar (3.15 mg/g) contents. Bioremediation of various textile industrial effluents saves the ecosystem from the harmful effects of hazardous dyes. The biological decolorization of the textile azo dyes was investigated under co-metabolic conditions. The degraded metabolites can be used to enhance crop productivity and for commercial application. This mandates the current and future research to develop economically feasible and environmentally sustainable wastewater treatment practices.

Different T cell related immunological profiles in COVID-19 patients compared to healthy controls.

In various pathological conditions, cellular immunity plays an important role in immune responses. Amongimmunecells, T lymphocytes pdomotecellular and humoralresponses as well as innate immunity. Therefore, careful investigation of these cells has a significant impact on accurate knowledge in COVID-19diseasepathogenesis. In current research, the frequency and function of various T lymphocytes involved in immune responses examined in SARS-CoV-2 patients with various disease severity compared to normal subjects. In order to make an accurate comparison among patients with various disease severity, this study was performed on asymptomatic recovered cases (n = 20), ICU hospitalized patients (n = 30), non-ICU hospitalized patients (n = 30), and normal subjects (n = 20). To precisely evaluate T cells activity following purification, their cytokine secretion activity was examined. Similarly, immediately after purification of Treg cells, their inhibitory activity on T cells was investigated. The results showed that COVID-19 patients with severe disease (ICU hospitalized patients) not only had a remarkable increase in Th1 and Th17 but also a considerable decrease in Th2 and Treg cells. More importantly, as the IL-17 and IFN-γ secretion was sharply increased in severe disease, the secretion of IL-10 and IL-4 was decreased. Furthermore, the inhibitory activity of Treg cells was reduced in severe disease patients in comparison to other groups. In severe COVID-19 disease, current findings indicate when the inflammatory arm of cellular immunity is significantly increased, a considerable reduction in anti-inflammatory and regulatory arm occurred.

Silencing STAT3 enhances sensitivity of cancer cells to doxorubicin and inhibits tumor progression.

AIMS: Despite extensive efforts to find new treatments, chemotherapy is still one of the first and foremost choices for cancer treatment. The main problems of using these drugs are the resistance of cancer cells and reducing their sensitivity to chemotherapy as well as the side effects of their systemic administration. Because STAT3 plays a very important role in the survival and susceptibility of cancer cells to apoptosis, we hypothesized that suppression of STAT3 expression could induce greater susceptibility to DOX-induced cancer cell death. MATERIALS AND METHODS: We used pegylated chitosan lactate nanoparticles (NPs) functionalized by TAT peptide and folate to deliver STAT3 siRNA and DOX to cancer cells simultaneously, both in vitro and in vivo. KEY FINDINGS: The results showed that NPs could effectively deliver siRNA and DOX to cancer cells, which was associated with suppression of STAT3 expression and increased induction of DOX-mediated cell death. Concomitant delivery of DOX and STAT3 siRNA also suppressed tumor growth in 4T1 and CT26 cancer models, which was associated with induction of anti-tumor immune responses. SIGNIFICANCE: These findings suggest that the use of NPs can be an effective strategy for the targeted delivery of STAT3-specific siRNA/DOX to cancer cells.

EP4 receptor as a novel promising therapeutic target in colon cancer.

The most prevalent malignancy that can occur in the gastrointestinal tract is colon cancer. The current treatment options for colon cancer patients include chemotherapy, surgery, radiotherapy, immunotherapy, and targeted therapy. Although the chance of curing the disease in the early stages is high, there is no cure for almost all patients with advanced and metastatic disease. It has been found that over-activation of cyclooxygenase 2 (COX-2), followed by the production of prostaglandin E2 (PGE2) in patients with colon cancer are significantly increased. The tumorigenic function of COX-2 is mainly due to its role in the production of PGE2. PGE2, as a main generated prostanoid, has an essential role in growth and survival of colon cancer cell's. PGE2 exerts various effects in colon cancer cells including enhanced expansion, angiogenesis, survival, invasion, and migration. The signaling of PGE2 via the EP4 receptor has been shown to induce colon tumorigenesis. Moreover, the expression levels of the EP4 receptor significantly affect tumor growth and development. Overexpression of EP4 by various mechanisms increases survival and tumor vasculature in colon cancer cells. It seems that the pathway starting with COX2, continuing with PGE2, and ending with EP4 can promote the spread and growth of colon cancer. Therefore, targeting the COX-2/PGE2/EP4 axis can be considered as a worthy therapeutic approach to treat colon cancer. In this review, we have examined the role and different mechanisms that the EP4 receptor is involved in the development of colon cancer.