Gold Nanoparticles Functionalized with 2-Thiouracil for Antiproliferative and Photothermal Therapies in Breast Cancer Cells.

Nanoparticles have been used to transport drugs to various body parts to treat cancer. Our interest is in gold nanoparticles (AuNPs) since they have the capacity to absorb light and convert it to heat, inducing cellular damage. This property is known as photothermal therapy (PTT) and has been studied in cancer treatment. In the present study, biocompatible citrate-reduced AuNPs were functionalized with a biologically active compound, 2-thiouracil (2-TU), of potential anticancer activity. Both the unfunctionalized (AuNPs) and functionalized (2-TU-AuNPs) were purified and characterized by UV-Vis absorption spectrophotometry, Zeta potential, and Transmission Electron Microscopy. Results showed monodispersed, spherical AuNPs with a mean core diameter of 20 ± 2 nm, a surface charge of -38 ± 5 mV, and a localized surface plasmon resonance peak at 520 nm. As a result of functionalization, the mean core diameter of 2-TU-AuNPs increased to 24 ± 4 nm, and the surface charge increased to -14 ± 1 mV. The functionalization of AuNPs and the load efficiency were further established through Raman spectroscopy and UV-Vis absorption spectrophotometry. The antiproliferative activities of AuNPs, 2-TU and 2-TU-AuNPs were examined by a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay in the MDA-MB-231 breast cancer cell line. It was established that AuNPs significantly enhanced the antiproliferative activity of 2-TU. Furthermore, the irradiation of the samples with visible light at 520 nm decreased the half-maximal inhibitory concentration by a factor of 2. Thus, the 2-TU drug concentration and its side effect during treatments could be significantly reduced by synergistically exploiting the antiproliferative activity of 2-TU loaded onto AuNPs and the PTT effect of AuNPs.

Experimental and Theoretical Screening of Core Gold Nanoparticles and Their Binding Mechanism to an Anticancer Drug, 2-Thiouracil.

This study demonstrated the capability of two readily available optical spectroscopy tools, namely UV-Vis absorption spectrophotometry and Raman/surface-enhanced Raman spectroscopy, to select in a rapid and noninvasive manner the most homogenous gold nanoparticle (AuNP) models and to identify their chemical binding mechanism to 2-thiouracil (2-TU). 2-TU is an anticancer drug of great promise in the antiproliferative and photothermal therapies of cancer. The citrate-capped AuNPs emerged as the most stable as well as time- and cost-effective AuNP model out of the three widely used colloidal nanocores (citrate-, borohydride-citrate-, and sodium dodecyl sulfate (SDS)-capped AuNPs) that were examined. 2-TU chemically attached to the relatively monodispersed AuNPs via a chemisorption mechanism. The 2-TU-AuNPs complex formed through the covalent bonding of the S atom of 2-TU to the nanosurface in a vertical orientation. The spectroscopic results were then confirmed with the help of density functional theory (DFT) calculations and other physicochemical characterization tools for nanomaterials such as transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential. Overall, the purified 2-TU-AuNPs were found to be spherical, had an average diameter of 25 ± 2 nm, a narrow size distribution (1-30 nm), a sharp localized surface plasmon resonance (LSPR) peak at 525 nm, and a negative surface charge (-14 mV).

Anticancer Potential of Betulonic Acid Derivatives.

Clinical trials have evidenced that several natural compounds, belonging to the phytochemical classes of alkaloids, terpenes, phenols and flavonoids, are effective for the management of various types of cancer. Latest research has proven that natural products and their semisynthetic variants may serve as a starting point for new drug candidates with a diversity of biological and pharmacological activities, designed to improve bioavailability, overcome cellular resistance, and enhance therapeutic efficacy. This review was designed to bring an update regarding the anticancer potential of betulonic acid and its semisynthetic derivatives. Chemical derivative structures of betulonic acid including amide, thiol, and piperidine groups, exert an amplification of the in vitro anticancer potential of betulonic acid. With the need for more mechanistic and in vivo data, some derivatives of betulonic acids may represent promising anticancer agents.

Melissa officinalis L. Aqueous Extract Exerts Antioxidant and Antiangiogenic Effects and Improves Physiological Skin Parameters.

Melissa officinalis (MO) is a medicinal plant well-known for its multiple pharmacological effects, including anti-inflammatory, anticancer and beneficial effects on skin recovery. In this context, the present study was aimed to investigate the in vitro and in vivo safety profile of an MO aqueous extract by assessing cell viability on normal (HaCaT-human keratinocytes) and tumor (A375-human melanoma) cells and its impact on physiological skin parameters by a non-invasive method. In addition, the antioxidant activity and the antiangiogenic potential of the extract were verified. A selective cytotoxic effect was noted in A375 cells, while no toxicity was noticed in healthy cells. The MO aqueous extract safety profile after topical application was investigated on SKH-1 mice, and an enhanced skin hydration and decreased erythema and transepidermal water loss levels were observed. The in ovo CAM assay, performed to investigate the potential modulating effect on the angiogenesis process and the blood vessels impact, indicated that at concentrations of 100 and 500 µg/mL, MO aqueous extract induced a reduction of thin capillaries. No signs of vascular toxicity were recorded at concentrations as high as 1000 µg/mL. The aqueous extract of MO leaves can be considered a promising candidate for skin disorders with impaired physiological skin parameters.

A Recent Insight Regarding the Phytochemistry and Bioactivity of Origanum vulgare L. Essential Oil.

Origanum vulgare L. is a widely used aromatic plant, especially due to its content in essential oil, mainly rich in carvacrol and thymol. The ethnopharmacological uses of Origanum vulgare L. essential oil (OEO) comprise digestive, respiratory, or dermatological disorders. The review focuses on the increasing number of recent studies investigating several biological activities of OEO. The bioactivities are in tight relation to the phytochemical profile of the essential oil, and also depend on taxonomic, climatic, and geographical characteristics of the plant material. The antibacterial, antifungal, antiparasitic, antioxidant, anti-inflammatory, antitumor, skin disorders beneficial effects, next to antihyperglycemic and anti-Alzheimer activities were reported and confirmed in multiple studies. Moreover, recent studies indicate a positive impact on skin disorders of OEO formulated as nanocarrier systems in order to improve its bioavailability and, thus, enhancing its therapeutic benefits. The review brings an up to date regarding the phytochemistry and bioactivity of Origanum vulgare L. essential oil, underlining also the most successful pharmaceutical formulation used for skin disorders.

Benign zinc oxide betaine-modified biochar nanocomposites for phosphate removal from aqueous solutions.

Phosphate is one of the most costly and complex environmental pollutants that leads to eutrophication, which decreases water quality and access to clean water. Among different adsorbents, biochar is one of the promising adsorbents for phosphate removal as well as heavy metal removal from an aqueous solution. In this study, biochar was impregnated with nano zinc oxide in the presence of glycine betaine. The Zinc Oxide Betaine-Modified Biochar Nanocomposites (ZnOBBNC) proved to be an excellent adsorbent for the removal of phosphate, exhibiting a maximum adsorption capacity of phosphate (265.5 mg. g-1) and fast adsorption kinetics (~100% removal at 15 min at 10 mg. L-1 phosphate and 3 g. L-1 nanocomposite dosage) in phosphate solution. The synthesis of these benign ZnOBBNC involves a process that is eco-friendly and economically feasible. From material characterization, we found that the ZnOBBNC has ~20-30 nm particle size, high surface area (100.01 m2. g-1), microporous (25.79 Å) structures, and 7.64% zinc content. The influence of pH (2-10), coexisting anions (Cl-, CO32-, NO3- and SO43-), initial phosphate concentration (10-500 mg. L-1), and ZnOBBNC dosage (0.5-5 g. L-1) were investigated in batch experiments. From the adsorption isotherms data, the adsorption of phosphate using ZnOBBNC followed Langmuir isotherm (R2 = 0.9616), confirming the mono-layered adsorption mechanism. The kinetic studies showed that the phosphate adsorption using ZnOBBNC followed the pseudo-second-order model (R2 = 1.0000), confirming the chemisorption adsorption mechanism with inner-sphere complexion. Our results demonstrated ZnOBBNC as a suitable, competitive candidate for phosphate removal from both mock lab-prepared and real field-collected wastewater samples when compared to commercial nanocomposites.

Cannabidiol-from Plant to Human Body: A Promising Bioactive Molecule with Multi-Target Effects in Cancer.

Cannabis sativa L. is a plant long used for its textile fibers, seed oil, and oleoresin with medicinal and psychoactive properties. It is the main source of phytocannabinoids, with over 100 compounds detected so far. In recent years, a lot of attention has been given to the main phytochemicals present in Cannabis sativa L., namely, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). Compared to THC, CBD has non-psychoactive effects, an advantage for clinical applications of anti-tumor benefits. The review is designed to provide an update regarding the multi-target effects of CBD in different types of cancer. The main focus is on the latest in vitro and in vivo studies that present data regarding the anti-proliferative, pro-apoptotic, cytotoxic, anti-invasive, anti-antiangiogenic, anti-inflammatory, and immunomodulatory properties of CBD together with their mechanisms of action. The latest clinical evidence of the anticancer effects of CBD is also outlined. Moreover, the main aspects of the pharmacological and toxicological profiles are given.

Assessment of the Antiangiogenic and Anti-Inflammatory Properties of a Maslinic Acid Derivative and its Potentiation using Zinc Chloride.

Maslinic acid is a pentacyclic triterpene with a plethora of biological activities, including anti-inflammatory, antioxidant, antimicrobial, cardioprotective, and antitumor effects. New derivatives with improved properties and broad-spectrum activity can be obtained following structural changes of the compound. The present study was aimed to characterize a benzylamide derivative of maslinic acid-benzyl (2α, 3ß) 2,3-diacetoxy-olean-12-en-28-amide (EM2)-with respect to the anti-angiogenic and anti-inflammatory effects in two in vivo experimental models. Consequently, the compound showed good tolerability and lack of irritation in the chorioallantoic membrane assay with no impairment of the normal angiogenic process during the tested stages of development. In the acute ear inflammation murine model, application of EM2 induced a mild anti-inflammatory effect that was potentiated by the association with zinc chloride (ZnCl2). A decrease in dermal thickness of mice ears was observed when EM2 and ZnCl2 were applied separately or in combination. Moreover, hyalinization of the dermis appeared only when EM2 was associated with ZnCl2, strongly suggesting the role of their combination in wound healing.

Romanian Wormwood (Artemisia absinthium L.): Physicochemical and Nutraceutical Screening.

Artemisia species are used worldwide for their antioxidant, antimicrobial and anti-inflammatory properties. This research was designed to investigate the phytochemical profile of two ethanolic extracts obtained from leaves and stems of A. absinthium L. as well as the biological potential (antioxidant activity, cytotoxic, anti-migratory and anti-inflammatory properties). Both plant materials showed quite similar thermogravimetric, FT-IR phenolic profile (high chlorogenic acid) with mild antioxidant capacity [ascorbic acid (0.02-0.1) > leaves (0.1-2.0) > stem (0.1-2.0)]. Alcoholic extracts from these plant materials showed a cytotoxic effect against A375 (melanoma) and MCF7 (breast adenocarcinoma) and affected less the non-malignant HaCaT cells (human keratinocytes) at 72 h post-stimulation and this same trend was observed in the anti-migratory (A375, MCF7 > HaCat) assay. Lastly, extracts ameliorated the pro-inflammatory effect of TPA (12-o-tetradecanoylphorbol-13-acetate) in mice ears, characterized by a diffuse neutrophil distribution with no exocytosis or micro-abscesses.

Quercetin exerts an inhibitory effect on cellular bioenergetics of the B164A5 murine melanoma cell line.

Modulation of mitochondrial bioenergetics and glycolysis in malignancies has recently emerged a potential chemotherapeutic strategy since numerous malignant cells have overcome inhibition of the glycolytic pathway by increasing mitochondrial ATP production. Quercetin is a flavonoid with antioxidant, antiangiogenic, and chemoprotective properties but the mitochondrial effects are less characterized. The present study was purported to assess the effects of quercetin on the bioenergetic profile of B164A5 murine melanoma cell line. The oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were measured at 24, 48, and 72 h of treatment of B164A5 murine melanoma cells with increasing concentrations (25, 50, 100, and 150 µM) of quercetin using the extracellular flux analyzer Seahorse XF24e (Seahorse Agilent). Analysis of mitochondrial function was performed in the presence of the classic modulators of the electron transport chain: oligomycin, FCCP, and rotenone. 72-h treatment with quercetin induced a dose-dependent decrease of all OCR parameters (basal respiration, proton leak, ATP turnover, maximal respiration, reserve capacity) as well as of ECAR. At variance, 48-h treatment induced a decrease of OCR and ECAR when quercetin was applied at 50, 100, and 150 µM, while the 24-h treatment induced a decrease of bioenergetic parameters only for the highest concentrations (100 and 150 µM) of the compound. Our data clearly demonstrated that quercetin elicited dose-dependent inhibitory effect on examined parameters of cellular bioenergetics that was most potent at 72 h of treatment. Thereby quercetin, modulating both glycolytic and mitochondrial pathways for ATP production, might be an efficient approach in killing cancer cells.

Drotaverine - a Concealed Cytostatic!

Drotaverine (also known as dihydroperparine or No-Spa® ) is an antispasmodic drug closely related to papaverin. Drotaverin also acts as a cytostatic compound for several human tumor cell lines and nonmalignant mouse fibroblasts, and EC50 values as low as 3.0 µM were observed in SRB assays for HT-29 human colorectal carcinoma cells. Small structural changes (e.g., aromatization, benzylic oxidation) led to a reduced activity or a complete loss of cytotoxicity. Staining of the cells with acridine orange showed the cell membrane of the dead cells to be still intact, and a slight G1/G0 arrest in the treated cells was observed after 24 h. Extra annexin V-FITC/PI assays and flow cytometry revealed drotaverine mainly to act as a cytostatic and only to a minor extent as cytotoxic agent.

Synthesis and proapoptotic activity of oleanolic acid derived amides.

Thirty-one different 3-O-acetyl-OA derived amides have been prepared and screened for their cytotoxic activity. In the SRB assays nearly all the carboxamides displayed good cytotoxicity in the low µM range for several human tumor cell lines. Low EC50 values were obtained especially for the picolinylamides 14-16, for a N-[2-(dimethylamino)-ethyl] derivative 27 and a N-[2-(pyrrolinyl)-ethyl] carboxamide 28. These compounds were submitted to an extensive biological testing and proved compound 15 to act mainly by an arrest of the tumor cells in the S phase of the cell cycle. Cell death occurred by autophagy while compounds 27 and 28 triggered apoptosis.

Antioxidant Extracts from Greek and Spanish Olive Leaves: Antimicrobial, Anticancer and Antiangiogenic Effects.

Olea europaea L. is the most valuable species of the Olea type, and its products offer a wide range of therapeutical uses. The olive tree has been extensively studied for its nourishing qualities, and the "Mediterranean diet", which includes virgin olive oil as a key dietary component, is strongly associated with a reduced risk of cardiovascular disease and various malignancies. Olive leaves, a by-product in the olive harvesting process, are valued as a resource for developing novel phytomedicines. For this purpose, two ethanolic extracts obtained from Olivae folium from Spain (OFS) and Greece (OFG) were investigated. Our findings contribute to a wider characterization of olive leaves. Both extracts displayed important amounts of phenolic compounds and pentacyclic triterpenes, OFG having higher concentrations of both polyphenols, such as oleuropein and lutein, as well as triterpenes, such as oleanolic acid and maslinic acid. The antioxidant capacity is similar for the two extracts, albeit slightly higher for OFG, possibly due to metal polyphenol complexes with antioxidant activity. The extracts elicited an antimicrobial effect at higher doses, especially against Gram-positive bacteria, such as Streptococcus pyogenes. The extract with lower inorganic content and higher content of polyphenols and triterpenic acids induced a strong anti-radical capacity, a selective cytotoxic effect, as well as antimigratory potential on A375 melanoma cells and antiangiogenic potential on the CAM. No irritability and a good tolerability were noted after evaluating the extracts on the in vivo Hen's Egg Test-Chorioallantoic Membrane (HET-CAM). Therefore, the present data are suggestive for the possible use of the two types of olive leaf products as high-antioxidant extracts, potentially impacting the healthcare system through their use as antimicrobial agents and as anticancer and anti-invasion treatments for melanoma.

Nanosilver: An Old Antibacterial Agent with Great Promise in the Fight against Antibiotic Resistance.

Antibiotic resistance in bacteria is a major problem worldwide that costs 55 billion USD annually for extended hospitalization, resource utilization, and additional treatment expenditures in the United States. This review examines the roles and forms of silver (e.g., bulk Ag, silver salts (AgNO3), and colloidal Ag) from antiquity to the present, and its eventual incorporation as silver nanoparticles (AgNPs) in numerous antibacterial consumer products and biomedical applications. The AgNP fabrication methods, physicochemical properties, and antibacterial mechanisms in Gram-positive and Gram-negative bacterial models are covered. The emphasis is on the problematic ESKAPE pathogens and the antibiotic-resistant pathogens of the greatest human health concern according to the World Health Organization. This review delineates the differences between each bacterial model, the role of the physicochemical properties of AgNPs in the interaction with pathogens, and the subsequent damage of AgNPs and Ag+ released by AgNPs on structural cellular components. In closing, the processes of antibiotic resistance attainment and how novel AgNP-antibiotic conjugates may synergistically reduce the growth of antibiotic-resistant pathogens are presented in light of promising examples, where antibiotic efficacy alone is decreased.

Comparison of In Vitro Antimelanoma and Antimicrobial Activity of 2,3-Indolo-betulinic Acid and Its Glycine Conjugates.

Malignant melanoma is one of the most pressing problems in the developing world. New therapeutic agents that might be effective in treating malignancies that have developed resistance to conventional medications are urgently required. Semisynthesis is an essential method for improving the biological activity and the therapeutic efficacy of natural product precursors. Semisynthetic derivatives of natural compounds are valuable sources of new drug candidates with a variety of pharmacological actions, including anticancer ones. Two novel semisynthetic derivatives of betulinic acid-N-(2,3-indolo-betulinoyl)diglycylglycine (BA1) and N-(2,3-indolo-betulinoyl)glycylglycine (BA2)-were designed and their antiproliferative, cytotoxic, and anti-migratory activity against A375 human melanoma cells was determined in comparison with known N-(2,3-indolo-betulinoyl)glycine (BA3), 2,3-indolo-betulinic acid (BA4) and naturally occurring betulinic acid (BI). A dose-dependent antiproliferative effect with IC50 values that ranged from 5.7 to 19.6 µM was observed in the series of all five compounds including betulinic acid. The novel compounds BA1 (IC50 = 5.7 µM) and BA2 (IC50 = 10.0 µM) were three times and two times more active than the parent cyclic structure B4 and natural BI. Additionally, compounds BA2, BA3, and BA4 possess antibacterial activity against Streptococcus pyogenes ATCC 19615 and Staphylococcus aureus ATCC 25923 with MIC values in the range of 13-16 µg/mL and 26-32 µg/mL, respectively. On the other hand, antifungal activity toward Candida albicans ATCC 10231 and Candida parapsilosis ATCC 22019 was found for compound BA3 with MIC 29 µg/mL. This is the first report of antibacterial and antifungal activity of 2,3-indolo-betulinic acid derivatives and also the first extended report on their anti-melanoma activity, which among others includes data on anti-migratory activity and shows the significance of amino acid side chain on the observed activity. The obtained data justify further research on the anti-melanoma and antimicrobial activity of 2,3-indolo-betulinic acid derivatives.

Cutaneous Polymeric-Micelles-Based Hydrogel Containing Origanum vulgare L. Essential Oil: In Vitro Release and Permeation, Angiogenesis, and Safety Profile In Ovo.

Origanum vulgare var. vulgare essential oil (OEO) is known as a natural product with multiple beneficial effects with application in dermatology. Oregano essential oil represents a potential natural therapeutic alternative for fibroepithelial polyps (FPs), commonly known as skin tags. Innovative formulations have been developed to improve the bioavailability and stability of essential oils. In this study, we aimed to evaluate the morphology of a polymeric-micelles-based hydrogel (OEO-PbH), the release and permeation profile of oregano essential oil, as well as to assess in vivo the potential effects on the degree of biocompatibility and the impact on angiogenesis in ovo, using a chick chorioallantoic membrane (CAM). Scanning electron microscopy (SEM) analysis indicated a regular aspect after the encapsulation process, while in vitro release studies showed a sustained release of the essential oil. None of the tested samples induced any irritation on the CAM and the limitation of the angiogenic process was noted. OEO-PbH, with a sustained release of OEO, potentially enhances the anti-angiogenic effect while being well tolerated and non-irritative by the vascularized CAM, especially on the blood vessels (BVs) in the presence of leptin treatment. This is the first evidence of in vivo antiangiogenic effects of a polymeric-micelle-loaded oregano essential oil, with further mechanistic insights for OEO-PbH formulation, involving leptin as a possible target. The findings suggest that the OEO-containing polymeric micelle hydrogel represents a potential future approach in the pathology of cutaneous FP and other angiogenesis-related conditions.

Biodistribution and toxicity of antimicrobial ionic silver (Ag+) and silver nanoparticle (AgNP+) species after oral exposure, in Sprague-Dawley rats.

Although antimicrobial nanosilver finds numerous applications in the health and food industries, the in vivo toxicity of positively charged silver nanoparticles (AgNPs+) and relevant controls are largely unexplored. This study investigates the relationship between the biodistribution and toxicity of the well-known cetyltrimethylammonium bromide (CTAB)-capped AgNPs+ in 6-weeks old female Sprague-Dawley rats, at sublethal doses. Amounts comparative to those leaked from food products or considered for animal feed were administered through daily water intake, for an 18-day period: AgNPs+ (40 µg mL-1), Ag+ (40 µg mL-1), antimicrobial CTAB+ (24 µg mL-1) and tap water. All exposures except for the water control had adverse effects on the health and systemic functions of rats (e.g., lethargy, hepatomegaly, splenomegaly, impediment of bone development, and/or heightened immune response). Although the total Ag accumulation in tissues (1.4-1.6 µg of Ag/g of liver, spleen, jejunum, and brain) was comparable for the two Ag species, AgNPs+ were generally more toxic than Ag+, particularly in spleen (0.8 µg Ag/g). Significantly reduced euthanasia time, alopecia, inflammatory responses in spleen, fragile veins, and enhanced lymphocytosis were observed only for AgNPs+. Overall, this study raises health concerns about the ingestion of capped-AgNPs+ or Ag+ by first-hand consumers and industry workers.

Understanding COVID-19 Situation in Nepal and Implications for SARS-CoV-2 Transmission and Management.

Background: The pandemic of Coronavirus Disease 2019 (COVID-19), one of the most infectious diseases in the modern history, is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and has had a profound health and economic toll, globally. This paper identifies the overall health status associated with COVID-19 pandemic in all 7 provinces of Nepal, a developing country in South Asia, analyzing data from January 2020 to February 2022. It focuses on the SARS-CoV-2 prevalence, transmission through wastewater and other routes, diagnostics, treatment options, and alternative medicines, thereby offering key perspectives for its management. Materials and Methods: Studies regarding coronavirus spanning the 2017 to 2022 period were searched on the web, Nepalese database, and Web of Science. Refined criteria included SARS-CoV-2 in wastewater of Nepal or worldwide. Demographic data (sex, age-group, and geographic location) were also obtained from websites and relevant reports of the Ministry of Health and Population (MOHP) of Nepal, ranging from January 2020 to February 2022. Moreover, trends concerning lockdown, business, and border activities in Nepal between February 2020 and October 2020 were evaluated. The viral dissemination pathways, diagnosis, and available treatment options, including the Ayurvedic medicine, were also examined. Results: Aerosols generated during the hospital, industrial, recreational, and household activities were found to contribute to the propagation of SARS-CoV-2 into environmental wastewater, thereby putting the surrounding communities at risk of infection. When lockdown ended and businesses opened in October 2020, the number of active cases of COVID-19 increased exponentially. Bagmati Province had the highest number of cases (53.84%), while the remaining 6 provinces tallied 46.16%. Kathmandu district had the highest number of COVID-19 cases (138, 319 cases), while Manang district had the smallest number of infections (81 cases). The male population was found to be predominantly infected (58.7%). The most affected age groups were the 31 to 40 years old males (25.92%) and the 21 to 30 years old females (26.85%). Conclusion: The pandemic impacted the public health and economic growth in our study duration. SARS-CoV-2 was prevalent in the wastewater of Nepal. The Terai districts and the megacities were mostly affected by SARS-CoV-2 infections. Working-age groups and males were identified as the highest risk groups. More investigations on the therapeutic and alternative cures are recommended. These findings may guide the researchers and professionals with handling the COVID-19 challenges in developing countries such as Nepal and better prepare for future pandemics.

An Up-To-Date Review Regarding Cutaneous Benefits of Origanum vulgare L. Essential Oil.

Due to the plethora of pharmacological activities reported in the literature, Origanum vulgare L. is a valuable aromatic plant for the medicine of the XXI century. Recent studies highlight that Origanum vulgare L. essential oil (OvEo) has gained attention in the dermatological field due to the cosmeceutical potential correlated with the presence of thymol and carvacrol. As a result of the fulminant expansion of bacterial resistance to antibiotics and the aggressiveness of skin infections, OvEo was extensively studied for its antimicrobial activity against Staphyloccocus spp. and Pseudomonas aeruginosa. Moreover, researchers have also assessed the anti-inflammatory activity of OvEo, suggesting its tissue remodeling and wound healing potential. Whereas OvEo comprises important biological activities that are used in a wide range of pathologies, recently, essential oils have shown great potential in the development of new therapeutic alternatives for skin disorders, such as acne, wounds or aging. Furthermore, substantial efforts have been committed to the development of modern formulations, such as microemulsions and nanoemulsions, in order to create the possibility for topical application. The review brings to the fore the most recent findings in the dermatological field regarding potential plant-based therapies involving OvEo, emphasizing the modern pharmaceutical formulation approaches and the cutaneous benefits in skin disorders.

Antimicrobial activity, in vitro anticancer effect (MCF-7 breast cancer cell line), antiangiogenic and immunomodulatory potentials of Populus nigra L. buds extract.

PURPOSE: The aim of this study was to evaluate the antioxidant potential, antimicrobial activity, the in vitro anticancer effect (tested on MCF-7 breast cancer cell line), as well as the antiangiogenic and immunomodulatory potential of Populus nigra L. bud (Pg) extract collected from the western part of Romania. RESULTS: Populus nigra L. bud extract presents an important antioxidant activity, due to the rich phytochemical composition. Regarding the biological activity, results have shown that poplar bud extract presents a significant inhibitory activity against Gram-positive bacteria and a dose-dependent decrease of MCF-7 tumor cell viability with an IC50 of 66.26 µg/mL, while not affecting healthy cells. Phenomena of early apoptotic events at the maximum concentration tested (150 µg/mL) were detected by Annexin V-PI double staining. The extract induced G0/G1 phase cell cycle arrest. In addition, Pg extract showed antiangiogenic potential on the chorioallantoic membrane. Also, at the highest concentration (150 µg/mL), good tolerability and no signs of toxicity upon vascular plexus were observed. Moreover, in low concentrations, the Pg extract had immunomodulatory activity on primary human dendritic cells by upregulating IL-12 and IL-23 subunits. CONCLUSION: The study concludes that poplar bud extract elicited antioxidant activity, antitumor properties on the breast cancer cell line, followed by an antiangiogenic effect and an immunomodulatory potential on human primary dendritic cells. The biological activity of Populus nigra L. buds extract may open new directions of research on the topic addressed.