Echinacea: Bioactive Compounds and Agronomy.

For centuries, medicinal plants have been used as sources of remedies and treatments for various disorders and diseases. Recently, there has been renewed interest in these plants due to their potential pharmaceutical properties, offering natural alternatives to synthetic drugs. Echinacea, among the world's most important medicinal plants, possesses immunological, antibacterial, antifungal, and antiviral properties. Nevertheless, there is a notable lack of thorough information regarding the echinacea species, underscoring the vital need for a comprehensive review paper to consolidate existing knowledge. The current review provides a thorough analysis of the existing knowledge on recent advances in understanding the physiology, secondary metabolites, agronomy, and ecology of echinacea plants, focusing on E. purpurea, E. angustifolia, and E. pallida. Pharmacologically advantageous effects of echinacea species on human health, particularly distinguished for its ability to safeguard the nervous system and combat cancer, are discussed. We also highlight challenges in echinacea research and provide insights into diverse approaches to boost the biosynthesis of secondary metabolites of interest in echinacea plants and optimize their large-scale farming. Various academic databases were employed to carry out an extensive literature review of publications from 2001 to 2024. The medicinal properties of echinacea plants are attributed to diverse classes of compounds, including caffeic acid derivatives (CADs), chicoric acid, echinacoside, chlorogenic acid, cynarine, phenolic and flavonoid compounds, polysaccharides, and alkylamides. Numerous critical issues have emerged, including the identification of active metabolites with limited bioavailability, the elucidation of specific molecular signaling pathways or targets linked to echinacoside effects, and the scarcity of robust clinical trials. This raises the overarching question of whether scientific inquiry can effectively contribute to harnessing the potential of natural compounds. A systematic review and analysis are essential to furnish insights and lay the groundwork for future research endeavors focused on the echinacea natural products.

Preparation and characterization of artemether-loaded niosomes in Leishmania major-induced cutaneous leishmaniasis.

Cutaneous leishmaniasis is the most prevalent form of leishmaniasis worldwide. Although various anti-leishmanial regimens have been considered, due to the lack of efficacy or occurrence of adverse reactions, design and development of novel topical delivery systems would be essential. This study aimed to prepare artemether (ART)-loaded niosomes and evaluate their anti-leishmanial effects against Leishmania major. ART-loaded niosomes were prepared through the thin-film hydration technique and characterized in terms of particle size, zeta potential, morphology, differential scanning calorimetry, drug loading, and drug release. Furthermore, anti-leishmanial effect of the preparation was assessed in vitro and in vivo. The prepared ART-loaded niosomes were spherical with an average diameter of about 100 and 300 nm with high encapsulation efficiencies of > 99%. The results of in vitro cytotoxicity revealed that ART-loaded niosomes had significantly higher anti-leishmanial activity, lower general toxicity, and higher selectivity index (SI). Half-maximal inhibitory concentration (IC50) values of ART, ART-loaded niosomes, and liposomal amphotericin B were 39.09, 15.12, and 20 µg/mL, respectively. Also, according to the in vivo study results, ART-loaded niosomes with an average size of 300 nm showed the highest anti-leishmanial effects in animal studies. ART-loaded niosomes would be promising topical drug delivery system for the management of cutaneous leishmaniasis.

microRNA 21 and long non-coding RNAs interplays underlie cancer pathophysiology: A narrative review.

Non-coding RNAs (ncRNAs) are a diverse group of functional RNA molecules that lack the ability to code for proteins. Despite missing this traditional role, ncRNAs have emerged as crucial regulators of various biological processes and have been implicated in the development and progression of many diseases, including cancer. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two prominent classes of ncRNAs that have emerged as key players in cancer pathophysiology. In particular, miR-21 has been reported to exhibit oncogenic roles in various forms of human cancer, including prostate, breast, lung, and colorectal cancer. In this context, miR-21 overexpression is closely associated with tumor proliferation, growth, invasion, angiogenesis, and chemoresistance, whereas miR-21 inactivation is linked to the regression of most tumor-related processes. Accordingly, miR-21 is a crucial modulator of various canonical oncogenic pathways such as PTEN/PI3K/Akt, Wnt/ß-catenin, STAT, p53, MMP2, and MMP9. Moreover, interplays between lncRNA and miRNA further complicate the regulatory mechanisms underlying tumor development and progression. In this regard, several lncRNAs have been found to interact with miR-21 and, by functioning as competitive endogenous RNAs (ceRNAs) or miRNA sponges, can modulate cancer tumorigenesis. This work presents and discusses recent findings highlighting the roles and pathophysiological implications of the miR-21-lncRNA regulatory axis in cancer occurrence, development, and progression. The data collected indicate that specific lncRNAs, such as MEG3, CASC2, and GAS5, are strongly associated with miR-21 in various types of cancer, including gastric, cervical, lung, and glioma. Indeed, these lncRNAs are well-known tumor suppressors and are commonly downregulated in different types of tumors. Conversely, by modulating various mechanisms and oncogenic signaling pathways, their overexpression has been linked with preventing tumor formation and development. This review highlights the significance of these regulatory pathways in cancer and their potential for use in cancer therapy as diagnostic and prognostic markers.

Evaluating an extraction-free sample preparation method for multiplex detection of SARS-Cov-2, influenza A/B, and RSV with implementation on a microfluidic chip.

Following the relaxation of COVID-19 restrictions, other respiratory viruses such as influenza and respiratory syncytial virus (RSV), whose transmission were decreased due to COVID-19 precautions, are rising again. Because of similar clinical features and reported co-infections, multiplex detection of SARS-CoV-2, influenza A/B, and RSV is required to use specific treatments. This study assessed an extraction-free sample preparation (heat treatment at 95°C for 3 minutes) for multiplex detection using rRT-PCR. Despite an observed Ct-delay (∆Ct) averageing 1.26 compared to the standard method, an acceptable total sensitivity of 92 % and a negative predictive value (NPV) of 96 % were obtained. Moreover, Implementation on a microfluidic chip demonstrated efficiency, maintaining an excellent correlation (R2=0.983) with the standard method. Combining this extraction-free procedure with rRT-PCR on a microfluidic chip seems promising, because it simplifies the design and reduces the cost and complexity of the integrated assay for multiplex detection of SARS-CoV-2, influenza A/B, and RSV.

Investigation the biological activities and the metabolite profiles of endophytic fungi isolated from Gundelia tournefortii L.

Endophytic fungi are microorganisms that are considered as a potential source of natural compounds, and can be applied in various industries. The aims of this research were molecular identification of endophytic fungi isolated from the Gundelia tournefortii stems, and investigation their biological activities as well as phenolic and fatty acid profile. Surface sterilized stems of G. tournefortii were placed on potato dextrose agar (PDA) to isolate the fungal endophytes. Genomic DNA was extracted by CTAB method, and PCR amplification was performed by ITS 1 and ITS 4 as primers. The enzyme production of endophytic fungi was determined based on the formation of a clear zone that appeared around the colonies of fungus. The anti-oxidant activity was evaluated by measuring the amount of free radicals DPPH. Also, the total phenol and flavonoid contents were measured obtained by Folin-Ciocalteu and aluminum chloride colorimetric methods, respectively. Moreover, the separation and identification of phenolic acids and fatty acids were done by HPLC and GC, respectively. Phylogenetic analysis was done based on the Internal Transcribed Spacer (ITS) region, and five isolates were identified as following: Aspergillus niger, Penicillium glabrum, Alternaria alternata, A. tenuissima, and Mucor circinelloides. Evaluation of the enzymatic properties showed that P. gabrum (31 ± 1.9 mm), and A. niger (23 ± 1.7) had more ability for producing pectinase and cellulase. The anti-oxidant activity of isolates showed that A. alternata extract (IC50 = 471 ± 29 µg/mL) had the highest anti-oxidant properties, followed by A. tenuissima extract (IC50 = 512 ± 19 µg/mL). Also, the extract of A. alternata had the greatest amount of total phenols and flavonoids contents (8.2 ± 0.4 mg GAL/g and 2.3 ± 0.3 mg QE/g, respectively). The quantification analysis of phenolic acid showed that rosmarinic acid, para-coumaric acid, and meta-coumaric acid (42.02 ± 1.31, 7.53 ± 0.19, 5.41 ± 0.21 mg/g, respectively) were the main phenolic acids in the studied fungi. The analysis of fatty acids confirmed that, in all fungi, the main fatty acids were stearic acid (27.9-35.2%), oleic acid (11.3-17.3%), palmitic acid (16.9-23.2%), linoleic acid (5.8-11.6%), and caprylic acid (6.3-10.9%). Our finding showed that endophytic fungi are a source of bioactive compounds, which could be used in various industries. This is the first report of endophytic fungi associated with G. tournefortii, which provides knowledge on their future use on biotechnological processes.

An Automated Single-Cell Droplet-Digital Microfluidic Platform for Monoclonal Antibody Discovery.

Monoclonal antibody (mAb) discovery plays a prominent role in diagnostic and therapeutic applications. Droplet microfluidics has become a standard technology for high-throughput screening of antibody-producing cells due to high droplet single-cell confinement frequency and rapid analysis and sorting of the cells of interest with their secreted mAbs. In this work, a new method is described for on-demand co-encapsulation of cells that eliminates the difficulties associated with washing in between consecutive steps inside the droplets and enables the washing and addition of fresh media. The new platform identifies hybridoma cells that are expressing antibodies of interest using antibody-characterization assays to find the best-performing or rare-cell antibody candidates.

A versatile theranostic magnetic polydopamine iron oxide NIR laser-responsive nanosystem containing doxorubicin for chemo-photothermal therapy of melanoma.

Theranostics nanoparticles (NPs) have recently received much attention in cancer imaging and treatment. This study aimed to develop a multifunctional nanosystem for the targeted delivery of photothermal and chemotherapy agents. Fe3O4 NPs were modified with polydopamine, bovine serum albumin, and loaded with DOX via a thermal-cleavable Azo linker (Fe3O4@PDA@BSA-DOX). The size of Fe3O4@PDA@BSA NPs was approximately 98 nm under the desired conditions. Because of the ability of Fe3O4 and PDA to convert light into heat, the temperature of Fe3O4@PDA@BSA NPs increased to approximately 47 °C within 10 min when exposed to an 808 nm NIR laser with a power density of 1.5 W/cm2. The heat generated by the NIR laser leads to the breaking of AZO linker and drug release. In vivo and in vitro results demonstrated that prepared NPs under laser irradiation successfully eradicated tumor cells without any significant toxicity effect. Moreover, the Fe3O4@PDA@BSA NPs exhibited the potential to function as a contrasting agent. These NPs could accumulate in tumors with the help of an external magnet, resulting in a significant enhancement in the quality of magnetic resonance imaging (MRI). The prepared novel multifunctional NPs seem to be an efficient system for imaging and combination therapy in melanoma.

Recent findings in methanotrophs: genetics, molecular ecology, and biopotential.

The potential consequences for mankind could be disastrous due to global warming, which arises from an increase in the average temperature on Earth. The elevation in temperature primarily stems from the escalation in the concentration of greenhouse gases (GHG) such as CO2, CH4, and N2O within the atmosphere. Among these gases, methane (CH4) is particularly significant in driving alterations to the worldwide climate. Methanotrophic bacteria possess the distinctive ability to employ methane as both as source of carbon and energy. These bacteria show great potential as exceptional biocatalysts in advancing C1 bioconversion technology. The present review describes recent findings in methanotrophs including aerobic and anaerobic methanotroph bacteria, phenotypic characteristics, biotechnological potential, their physiology, ecology, and native multi-carbon utilizing pathways, and their molecular biology. The existing understanding of methanogenesis and methanotrophy in soil, as well as anaerobic methane oxidation and methanotrophy in temperate and extreme environments, is also covered in this discussion. New types of methanogens and communities of methanotrophic bacteria have been identified from various ecosystems and thoroughly examined for a range of biotechnological uses. Grasping the processes of methanogenesis and methanotrophy holds significant importance in the development of innovative agricultural techniques and industrial procedures that contribute to a more favorable equilibrium of GHG. This current review centers on the diversity of emerging methanogen and methanotroph species and their effects on the environment. By amalgamating advanced genetic analysis with ecological insights, this study pioneers a holistic approach to unraveling the biopotential of methanotrophs, offering unprecedented avenues for biotechnological applications. KEY POINTS: • The physiology of methanotrophic bacteria is fundamentally determined. • Native multi-carbon utilizing pathways in methanotrophic bacteria are summarized. • The genes responsible for encoding methane monooxygenase are discussed.

Development of kojic acid loaded collagen-chitosan nanoparticle as skin lightener product: in vitro and in vivo assessment.

In the present study, an ionic gelation and ultrasonic approach was performed to produce kojic acid (KA) loaded chitosan(CS)/collagen(CN) nanoparticle(NP) (CSCN-NP) which aimed to increase the dermal delivery and anti-pigmentation effect. To optimize the CSCN-NP the effect of the amount of CN was investigated. The results showed that increasing CN from 0 to 500 mg increased the mean particle size and entrapment efficiency of KA-CSCN-NP from 266.07 ± 9.30 nm to 404.23 ± 9.44 nm and 17.37 ± 2.06% to 82.34 ± 2.16%, respectively. Differential scanning calorimetry confirmed the amorphous form of KA in CSCN-NP, while scanning electron microscopy revealed that the nanoparticles were spherical. There was no chemical interaction between KA and the other components base on attenuated total reflectance-Fourier transform infrared spectroscopy. The skin permeability test showed that KA-CSCN-NP gel delivered more KA to the dermal layers (29.16 ± 1.67% or 537.26 ± 537.26 µg/cm2) and receiver compartment (15.04 ± 1.47% or 277.15 ± 27.22 µg/cm2) compared to KA plain gel. In vitro cytotoxicity assay demonstrated that the improved KA-CSCN-NP was non-toxic. Dermal irritating test on Wistar rats showed that the KA gel was non-irritating. Furthermore, KA-CSCN-NP was found to inhibit melanin formation to a greater extent than free KA and significantly inhibited L-dopa auto-oxidation (94.80 ± 2.41%) compared to pure kojic acid solution (75.28 ± 3.22%). The observations of this study revealed that the produced KA-CSCN-NP might be used as a potential nano-vehicle for KA dermal administration, thereby opening up innovative options for the management of hyper-melanogenesis problems.

Low-Dose Methotrexate and Serious Adverse Events Among Older Adults With Chronic Kidney Disease.

Importance: Low-dose methotrexate is used to treat rheumatoid arthritis and psoriasis. Due to its kidney elimination, better evidence is needed to inform its safety in adults with chronic kidney disease (CKD). Objectives: To compare the 90-day risk of serious adverse events among adults with CKD who started low-dose methotrexate vs those who started hydroxychloroquine and to compare the risk of serious adverse events among adults with CKD starting 2 distinct doses of methotrexate vs those starting hydroxychloroquine. Design, Setting, and Participants: This retrospective, population-based, new-user cohort study was conducted in Ontario, Canada (2008-2021) using linked administrative health care data. Adults aged 66 years or older with CKD (defined as an estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2 but not receiving dialysis) who started low-dose methotrexate (n = 2309) were matched 1:1 with those who started hydroxychloroquine. Exposure: Low-dose methotrexate (5-35 mg/wk) vs hydroxychloroquine (200-400 mg/d). Main Outcome and Measure: The primary outcome was a composite of serious adverse events: a hospital visit with myelosuppression, sepsis, pneumotoxic effects, or hepatotoxic effects within 90 days of starting the study drug. Prespecified subgroup analyses were conducted by eGFR category. Propensity score matching was used to balance comparison groups on indicators of baseline health. Risk ratios (RRs) were obtained using modified Poisson regression, and risk differences (RDs) using binomial regression. Results: In a propensity score-matched cohort of 4618 adults with CKD (3192 [69%] women; median [IQR] age, 76 [71-82] years), the primary outcome was higher in patients who started low-dose methotrexate vs those who started hydroxychloroquine (82 of 2309 [3.55%] vs 40 of 2309 [1.73%]; RR, 2.05 (95% CI, 1.42-2.96); RD, 1.82% [95% CI, 0.91%-2.73%]). In subgroup analysis, the risks increased progressively at lower eGFR (eg, eGFR <45 mL/min/1.73 m2: RR, 2.79 [95% CI, 1.51-5.13]). In the secondary comparison with hydroxychloroquine, methotrexate users at 15 to 35 mg/wk had a higher risk of the primary outcome. Conclusions and Relevance: In this cohort of 4618 older patients with CKD, the 90-day risk of serious adverse events was higher among those who started low-dose methotrexate than those who started hydroxychloroquine. If verified, these risks should be balanced against the benefits of low-dose methotrexate use.

Recent advances in various bio-applications of bacteria-derived outer membrane vesicles.

Outer membrane vesicles (OMVs) are spherical nanoparticles released from gram-negative bacteria. OMVs were originally classified into native 'nOMVs' (produced naturally from budding of bacteria) and non-native (produced by mechanical means). nOMVs and detergent (dOMVs) are isolated from cell supernatant without any detergent cell disruption techniques and through detergent extraction, respectively. Growth stages and conditions e.g. different stress factors, including temperature, nutrition deficiency, and exposure to hazardous chemical agents can affect the yield of OMVs production and OMVs content. Because of the presence of bacterial antigens, pathogen-associated molecular patterns (PAMPs), various proteins and the vesicle structure, OMVs have been developed in many biomedical applications. OMVs due to their size can be phagocytized by APCs, enter lymph vessels, transport antigens efficiently, and induce both T and B cells immune responses. Non-engineered OMVs have been frequently used as vaccines against different bacterial and viral infections, and various cancers. OMVs can also be used in combination with different antigens as an attractive vaccine adjuvant. Indeed, foreign antigens from target microorganisms can be trapped in the lumen of nonpathogenic vesicles or can be displayed on the surface through bacterial membrane protein to increase the immunogenicity of the antigens. In this review, different factors affecting OMV production including time of cultivation, growth media, stress conditions and genetic manipulations to enhance vesiculation will be described. Furthermore, recent advances in various biological applications of OMVs such as vaccine, drug delivery, cancer therapy, and enzyme carrier are discussed. Generally, the application of OMVs as vaccine carrier in three categories (i.e., non-engineered OMVs, OMVs as an adjuvant, recombinant OMVs (rOMVs)), as delivery system for small interfering RNA and therapeutic agents, and as enzymes carrier will be discussed.

Nanohybrid Based on (Mn, Zn) Ferrite Nanoparticles Functionalized With Chitosan and Sodium Alginate for Loading of Curcumin Against Human Breast Cancer Cells.

This study reports on the synthesis of Mn1 - xZnxFe2O4 (Mn, Zn ferrite) magnetic nanoparticles (MNPs) as drug delivery carriers for effective therapeutic outcomes. The MNPs were prepared using the coprecipitation method, and their magnetic properties were investigated based on their composition. Among the compositions tested, Mn0.8Zn0.2Fe2O4 MNPs exhibited superparamagnetic properties with a saturation magnetization moment of 34.6 emu/g at room temperature (25°C). To enhance the water solubility of curcumin (Cur), known for its hydrophobic nature, it was successfully loaded onto alginate (Alg)/chitosan (Chit)@Mn0.8Zn0.2Fe2O4 nanoparticles (NPs). The nanocomposite was characterized by field emission scanning electron microscopy (FE-SEM) which revealed a particle size of approximately 20 nm. The crystalline structure of the NPs was analyzed using X-ray diffraction, while Fourier-transform infrared (FTIR), energy-dispersive X-ray, and map analysis techniques were employed for further characterization. In terms of drug release, there was an initial burst release of Cur (around 18%) within the first hour, followed by a slower release (approximately 61%) over the next 36 h. The anti-tumor properties of the Cur-loaded NPs were evaluated using the Methyl Thiazol Tetrazolium (MTT) assay and quantitative real-time polymerase chain reaction. The MTT assay confirmed a higher cytotoxic effect of Cur-loaded Alg/Chit@Mn0.8Zn0.2Fe2O4 NPs on the MCF-7 breast cancer cell line compared to free Cur, highlighting the significance of incorporating Cur into nano-sized carrier systems.

Evaluation of sleep quality in faculty members of Isfahan university of medical sciences.

BACKGROUND: Sleep disorders can significantly impair the quality of life and daily functions. Evaluating sleep quality can provide valuable information about working conditions. This study aims to evaluate the sleep quality of faculty members at Isfahan University of Medical Sciences (IUMS). METHODS: This descriptive-analytic study was conducted from 2020 to 2021, involving 106 faculty members from the medical school. A questionnaire collected demographic information, including age, sex, height, weight, body mass index (BMI), level of education, history of faculty membership, major, working hours during the day and night, residency place, and medical history. The Pittsburgh Sleep Quality Index (PSQI) and Symptom Checklist-25 (SCL-25) questionnaire were used to assess participants' sleep quality. Data were compared between clinicians and basic science faculty members. RESULTS: PSQI subtypes were examined among the participants. The total PSQI score was 6.20±3.4. A comparison of PSQI scores and subtypes based on age categories did not show any significant differences (P > 0.05 for all). Clinicians had significantly lower total PSQI scores (P=0.044), sleep latency (P=0.024), sleep disturbances (P=0.012), and daytime dysfunction (P=0.022). Additionally, clinicians had a lower severity of sleep latency (P=0.024), sleep disturbances (P=0.012), and total PSQI score (P=0.044). However, clinicians exhibited a higher intensity of daytime dysfunction (P=0.022). CONCLUSION: Faculty members exhibited a high prevalence of sleep disorders, with the most common disorders being sleep disturbance and high sleep latency. The prevalence of sleep disorders was higher among basic science faculty members compared to clinicians.

Exploring nursing students' perceptions from nursing role function (SP-NRF) during the COVID-19 pandemic in Ardabil Province: a cross sectional study from Iran.

BACKGROUND: Perception of nursing roles among nursing students significantly influences their active engagement in nursing processes and care delivery. However, there is evidence to suggest that students' interest in and perceptions from the nursing profession at the undergraduate level are often insufficient. OBJECTIVE: This study aimed to assess nursing students' perceptions of nursing role function and identify areas that require improvement. METHODS: A cross-sectional study was conducted in 2021 among nursing students in the third- and fourth-years from three faculties in the Ardabil Province. The participants were selected through census sampling. The data were collected through interviews with the Standardized Professional Nursing Role Function (SP-NRF) questionnaire. Statistical analysis was performed using the SPSS-18 software at a significance level of less than 0.05. RESULTS: A total of 320 nursing students participated in this study. The mean score for nursing role perception was 223.1 ± 20.3 out of 255. The results indicated significant gender differences in the mean scores of perception of the nursing role function, particularly in the supportive, professional-moral care, and professional-educational dimensions. Women scored significantly higher than men did (P < .05). Additionally, students who obtained a mean score of 19 to 20 (A) had significantly higher total scores in perception of the nursing role function than other students. Furthermore, a positive correlation was observed between students' interest in nursing and their perceived ability with nursing role perception (r = .282, P < .01) and all its dimensions. CONCLUSION: Overall, nursing students demonstrated a favorable perception of nursing role function. However, their perception of mental and spiritual care was relatively weak. These findings highlight the need to review nursing education programs and incorporate the spiritual care dimension to enhance students' understanding of and preparation for their role as nurses.

Platelets and platelet-derived vesicles as an innovative cellular and subcellular platform for managing multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a progressive inflammatory autoimmune disease that involves young individuals. The drug delivery systems now are available for this disease have chronic and non-targeted effects on the patients. Because of the presence of BBB (blood-brain-barrier), their concentration in the CNS (central nervous system) is low. Because of this flaw, it is critical to use innovative active targeted drug delivery methods. RESULT: Platelets are blood cells that circulate freely and play an important role in blood hemostasis. In this review, we emphasize the various roles of activated platelets in the inflammatory condition to recruit other cells to the injured area and limit inflammation. Besides, the activated platelets in the different stages of the MS disease play a significant role in limiting the progression of inflammation in the peripheral area and CNS. DISCUSSION: This evidence indicates that a platelet-based drug delivery system can be an efficient biomimetic candidate for drug targeting to the CNS and limiting the inflammation in the peripheral and central areas for MS therapy.

Carcinogenic and non-carcinogenic risk assessment of exposure to trace elements in groundwater resources of Sari city, Iran.

The daily intake of trace elements through water resources and their adverse health effects is a critical issue. The purpose of this research was to assess the carcinogenic and non-carcinogenic risks of exposure to iron (Fe), copper (Cu), manganese (Mn), zinc (Zn), chromium (Cr), lead (Pb), and arsenic (As) in groundwater resources of Sari city, Iran. The concentrations of the trace elements in a total number of 66 samples from the groundwater sources were measured using inductively coupled plasma mass spectrometry (ICP-MS). The hazard index (HI) levels of exposure to the trace elements from the groundwater sources for adults, teenagers, and children were 0.65, 0.83, and 1.08, respectively. The carcinogenic risk values of Cr and As in the groundwater sources for children, teenagers, and adults were 0.0001, 0.00009, 0.00007, 0.0003, 0.0002, and 0.0001, respectively, causing a total carcinogenic risk value higher than the acceptable range, and removing Cr and As from the groundwater resources is recommended for safe community water supply.

Novel 2-substituted-5-(4-chloro-2-phenoxy)phenyl-1,3,4-oxadiazole derivatives, ligands of GABAA/benzodiazepine receptor complex: Design, synthesis, radioligand binding assay, and pharmacological evaluation.

Agonists of Benzodiazepine (BZD) receptor are exhaustively used in the control of muscle spasms, seizure, anxiety, and insomnia. BZDs have some unwanted effects; therefore, the development of new BZD receptor agonists with better efficacy and fewer unwanted effects is one of the subjects of interest. In this study, based on the pharmacophore/receptor model of the BZD binding site of GABAA receptors, a series of new 2-substituted-5-(4-chloro-2-phenoxy)phenyl-1,3,4-oxadiazole derivatives (6a-f) were designed. Energy minima conformers of the designed compounds and diazepam were well matched in conformational analysis and showed proper interaction with the BZD-binding site of the GABAA receptor model (α1ß2ϒ2) in docking studies. The designed compounds were synthesized in acceptable yield and evaluated for their in vitro affinity to the benzodiazepine receptor of rat brains by radioligand receptor binding assay. The results demonstrated that the affinities of most of the novel compounds were even higher than diazepam. The novel compound 6a with the best affinity in radioligand receptor binding assay (Ki=0.44 nM and IC50= 0.73±0.17 nM) had considerable hypnotic activity and weak anticonvulsant and anxiolytic effects with no negative effect on memory in animal models. Flumazenil as a selective benzodiazepine receptor antagonist was able to prevent hypnotic and anticonvulsant effects of 6a indicating the role of BZD receptors in these effects.

Progress in targeting PTEN/PI3K/Akt axis in glioblastoma therapy: Revisiting molecular interactions.

Glioblastoma (GBM) is one of the most malignant cancers of central nervous system and due to its sensitive location, surgical resection has high risk and therefore, chemotherapy and radiotherapy are utilized for its treatment. However, chemoresistance and radio-resistance are other problems in GBM treatment. Hence, new therapies based on genes are recommended for treatment of GBM. PTEN is a tumor-suppressor operator in cancer that inhibits PI3K/Akt/mTOR axis in diminishing growth, metastasis and drug resistance. In the current review, the function of PTEN/PI3K/Akt axis in GBM progression is evaluated. Mutation or depletion of PTEN leads to increase in GBM progression. Low expression level of PTEN mediates poor prognosis in GBM and by increasing proliferation and invasion, promotes malignancy of tumor cells. Moreover, loss of PTEN signaling can result in therapy resistance in GBM. Activation of PTEN signaling impairs GBM metabolism via glycolysis inhibition. In contrast to PTEN, PI3K/Akt signaling has oncogenic function and during tumor progression, expression level of PI3K/Akt enhances. PI3K/Akt signaling shows positive association with oncogenic pathways and its expression similar to PTEN signaling, is regulated by non-coding RNAs. PTEN upregulation and PI3K/Akt signaling inhibition by anti-cancer agents can be beneficial in interfering GBM progression. This review emphasizes on the signaling networks related to PTEN/PI3K/Akt and provides new insights for targeting this axis in effective GBM treatment.

Lessons learned from COVID-19 pandemic: Vaccine platform is a key player.

The SARS-CoV-2 outbreak and emergence of COVID-19 resulted in the development of different vaccines based on various platforms to combat the disease. While the conventional platforms of inactivated/live attenuated, subunit proteins and virus-like particles (VLPs) have provided efficient and safe vaccines, novel platforms of viral vector- and nucleic acid-based vaccines opened up new horizons for vaccine development. The emergence of COVID-19 pandemic showed that the availability of platforms with high possibility of quick translation from bench to bedside is a prerequisite step in vaccine development in pandemics. Moreover, parallel development of different platforms as well as considering the shipping, storage condition, distribution infrastructure and route of administration are key players for successful and robust response. This review highlights the lessons learned from the current COVID-19 pandemic in terms of vaccine development to provide quick response to future outbreaks of infectious diseases and the importance of vaccine platform in its storage condition and shipping. Finally, the potential application of current COVID-19 vaccine platforms in the treatment of non-infectious diseases has been discussed.