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Background and Aim: Total antioxidant capacity (TAC) of the tissue is an important factor in determining the physiological or physio-pathological function of oxygen reactive spices. Release of reactive oxygen species (ROS) in dermal wounds, leads to necrosis as well as apoptosis and tissue loss. Management of the risk factors for tissue loss due to flap failure can reduce risk factors with resultant improvement in the survival and efficacy of the flaps. Materials and Methods: 40 Sprauge-Dawkey rats were divided into 4 groups (1) sham group with an 8×3 cm skin cut without skin elevation (2) Flap group with an 8×3 cm skin cut with skin elevation (3) cymophenol group treated with cymophenol (25 mg/kg/day) (4) cymophenol group treated with cymophenol (50 mg/kg/day) after surgery. After one week, percentage of the living tissue, superoxide dismutase (SOD) activity and amount of malondialdehyde (MDA) were measured in the groups and the proximity results were extracted. Using GraphPad Prism 6 software, data were analyzed and compared by ANOVA and Tukey test. Results: Cymophenol application decreased the amount of malondialdehyde (p

Background and Objective: Onosma dichroanthum Boiss. is one of the most important mountainous medicinal plants in Iran. This study was done to determine the biomechanical evaluation of root extract ointment of Onosma dichroanthum Boiss. on wound healing in rats. Materials and Methods: In this experimental study, 18 male adult Wistar rats were randomly allocated into control (I), vehicle (II) and treated group with ointment containing of extract 1% of root of Onosma dichroanthum Boiss., (III). 20 mm vertical skin incision wound were made on rats back side. The assessment of the wound healing was carried out at day 14. At the end of study, rats were sacrificed, skin sample were extracted and evaluated by biomechanical method (maximum force, elastic stiffness, energy absorption). Results: There was no significant difference in biomechanical parameters among the treated, vehicle and control groups. Conclusion: Topical application of Onosma dichroanthum Boiss. root have no effect on healing of skin wound in animal model.

Alzheimer's disease (AD) is a progressive condition marked by multiple underlying mechanisms. Therefore, the investigation of natural products that can target multiple pathways presents a potential gate for the understanding and management of AD. This study aimed to assess the neuroprotective effects of the hydroalcoholic extract of Dracocephalum moldavica (DM) on cognitive impairment, biomarker changes, and putative metabolic pathways in a rat model of AD induced by intracerebroventricular streptozotocin (ICV-STZ). The DM extract was standardized and quantified based on examining total phenolic, total flavonoid, rosmarinic acid, and quercetin contents using colorimetry and high-performance liquid chromatography (HPLC) methods. The antioxidant potential of the extract was evaluated by 2,2-Diphenyl-1-picrylhydrazyl and nitric oxide radical scavenging assays. Male Wistar rats were injected with STZ (3 mg/kg, single dose, bilateral ICV) to induce a sporadic AD (sAD) model. Following model induction, rats were orally administered with DM extract (100, 200, and 400 mg/kg/day) or donepezil (5 mg/kg/day) for 21 days. Cognitive function was assessed using the radial arm water maze behavioral test. The histopathological evaluations were conducted in the cortex and hippocampus regions. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) was used to assess metabolite changes in various brain regions. DM extract significantly attenuated cognitive dysfunction induced by ICV-STZ according to behavioral and histopathological investigations. Thirty-two discriminating metabolites related to the amino acid metabolism; the glutamate/gamma-aminobutyric acid/glutamine cycle; nucleotide metabolism; lipid metabolism (glycerophospholipids, sphingomyelins, ceramides, phosphatidylserines, and prostaglandins), and glucose metabolic pathways were identified in the brains of rats with sAD simultaneously for the first time in this model. Polyphenols in DM extract may contribute to the regulation of these pathways. After treatment with DM extract, 10 metabolites from the 32 identified ones were altered in the brain tissue of a rat model of sAD, most commonly at doses of 200 and 400 mg/kg. In conclusion, this study demonstrates the neuroprotective potential of DM by upregulation/downregulation of various pathophysiological biomarkers such as adenine, glycerophosphoglycerol, inosine, prostaglandins, and sphingomyelin induced by ICV-STZ in sAD. These findings are consistent with cognitive behavioral results and histopathological outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025 Published by Elsevier Ltd.)

Wheat germ is one of the richest natural sources of polyamines, especially spermidine. Cell proliferation property of polyamines has given them inductive effects in the reduction of a variety of chronic diseases and fertility enhancement. Preparing a polyamine-rich extract powder from wheat germ for use in supplements is the aim of the present study. For the first time, the effects of three independent variables of clean-up replicate (A), extraction time (B), and solid-to-liquid ratio (C) on the response of total spermidine content (Y) were investigated using a central composite design optimizing polyamine enrichment. The optimal extraction conditions were 7 h, 3 clean-up replicates, and 1:4 solid to liquid ratio. This is the first production report of spermidine-enriched powder for encapsulation purposes. To obtain an acceptable rheological property, the polyamine-enriched extract was spray dried together with a selected group of excipients, among which glucose was evidenced as the best choice based on encapsulation properties., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare. All co-authors have seen and agree with the contents of manuscript and there is no financial interest to report. We certify that the submission is original work and is not under review at any other publication., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Current studies have shown emerging roles of lncRNAs in the pathobiology of neuropathic pain and migraine., Methods: We have chosen five lncRNAs, namely, PVT1, DSCAM-AS, MEG3, LINC-ROR, and SPRY4-IT1 for assessment of their expression in the circulation of migraineurs., Results: Expressions of PVT1 and MEG3 were higher in total migraineurs and both subgroups compared with controls (P < 0.0001). Meanwhile, expression of both lncRNA was higher in migraineurs with aura versus migraineurs without aura (P value < 0.0001 and = 0.01, respectively). Expression of DSCAM-AS1 was not different between any groups of patients compared with controls. Expression of LINC-ROR was elevated in total patients and patients with aura compared with controls (P value = 0.0002 and < 0.0001, respectively). It was also over-expressed in migraineurs with aura vs. migraineurs without aura (P = 0.01). Finally, expression of SPRY4-IT1 was higher in total patients and patients without aura compared with migraine-free persons (P values < 0.0001). Expressions of five mentioned lncRNAs were correlated in almost all study groups. In patients without aura, correlations were significant only for two pairs (SPRY4-IT1/PVT1 and SPRY4-IT1/DSCAM-AS1). PVT1 and MEG3 had the appropriate AUC, sensitivity and specificity values for separation of total migraineurs and both groups of patients from controls. The highest AUC value was reported for PVT1 in separation of migraineurs with aura from healthy controls (AUC = 0.98)., Conclusion: Cumulatively, our study shows evidence for deregulation of lncRNAs in migraineurs., (© 2024. The Author(s) under exclusive licence to Belgian Neurological Society.)

Background: The wound healing process, restoring the functionality of the damaged tissue, can be accelerated by various compounds. The recent experimental analysis highlights the beneficial effects of phytochemicals in improving skin regeneration and wound healing. In traditional medicine, one of the widespread plants used for treating different injuries or skin afflictions is Galium aparine L. (GA). Besides, previously reported chemical compounds of GA suggested its therapeutic effects for the wound healing process, yet its regulatory effects on the cellular and molecular stages of the wound healing process have not been investigated., Methods: In the present study, the phytochemical profile of the GA extract was analyzed using HPTLC fingerprinting, and further scientific evaluation of its phytochemicals was done. The wound-healing effects of GA extract were explored at the cellular and molecular levels while accounting for cell toxicity. The wound closure enhancing effect, antibacterial activity, and antioxidant activity were assessed., Results: The HPTLC fingerprinting of the GA extract proved its previously reported phytochemical profile including phenols, flavonoids, tannins, plant acids, ergot alkaloids, flavonoids, anthraquinones, terpenoids, sterols, salicin, lipophilic compounds, saponins, iridoids, and heterocyclic nitrogen compounds. Antimicrobial assessment, of the extract, indicated the more susceptibility of S. aureus to the inhibitory effects of GA rather than E. coli and S. epidermidis. DPPH test results revealed the antioxidant property of GA extract, which was comparable to ascorbic acid. The results of the viability assay showed no cytotoxicity effects on human umbilical endothelial cell (HUVEC) and normal human dermal fibroblast (NHDF) cell lines treated with different concentrations of whole plant extract and cell viability increased in a dose-dependent manner. The results of the scratch assay showed improved cell migration and wound closure., Conclusions: This study shows the anti-oxidant, anti-microbial, and in vitro wound healing wound-healing effects of GA hydroalcoholic extract, which aligns with its use in traditional medicine. No cytotoxicity effects were shown. The results from this study can be the basis for further investigations such as animal models and phytochemical studies. Further evaluation of its effects on mechanisms and signaling pathways involved in the wound healing processes such as angiogenesis and cell proliferation can provide novel insights into the potential therapeutic effects of the GA extract., (© 2024. The Author(s).)

Phytochemical analysis of aerial flowering parts of Euphorbia spinidens Bornm. ex Prokh. from Euphorbiaceae family (local name: Farfion-e-dandaneh-khari) led to the isolation of five diterpenes based on myrsinane backbone. Using HRESI-MS, 1D, and 2D NMR, they were identified as two previously unreported: 33,7,14,15(β)-tetraacetyl-5(α)-butanoyl-13α(17)epoxy-8,10(18)-myrsinadiene ( 1 ), 7,14,15(β)-triacetyl-3(β),5(α)-dibutanoyl-13α(17)epoxy-8,10(18)-myrsinadiene ( 2 ), and three known diterpenes: 3,7,14,15(β)-tetraacetyl-5(α)-propanoyl-13(17)-epoxy-8,10(18)-myrsinadiene ( 3 ), and 3,7,10,14,15(β)-Pentaacetyl-5(α)-butanoyl-13,17-epoxy-8-myrsinene ( 4 ), 3,7,10,14,15(β)-pentaacetyl-5(α)-propanoyl-13,17-epoxy-8-myrsinene ( 5 ). Compound 5 was previously reported in the roots of the same plant but without NMR data. Therefore, its mass pattern, 1 H-, and 13 C-NMR data are reported. The cytotoxicity and proapoptotic properties of 1 - 3 were evaluated against EJ-138 bladder carcinoma cells through standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay for cytotoxicity screening and annexin V-FITC/PI apoptosis detection kit. In the cytotoxicity assay, the IC 50 values found against EJ-138 were: ( 1 ) 41.6 ± 3.54 μM; ( 2 ) 38.4 ± 2.54 μM; ( 3 ) 57.3 ± 5.4 μM, whilst the IC 50  value of doxorubicin was 1.7 ± 0.3 μM, respectively. In apoptosis assay, total apoptosis of compounds 1 - 3 at higher concentrations (100 μM) were 57.6 ± 3.54, 46.3 ± 2.82, and 57.2 ± 4.35%, respectively.

Ethnopharmacological Relevance: Oliveria decumbens Vent. (Apiaceae), a single aromatic species in Iran, is traditionally used for healing inflammation, gastrointestinal disorders, and infections., Aim of the Study: Regarding the importance of O. decumbens in traditional medicine, we aimed to set out the plant's biological screening and analyze the chemical components of the active fractions., Materials and Methods: Air-dried O. decumbens aerial parts were macerated by ethanol:water (70:30). Using a liquid-liquid extraction (LLE) technique, n-hexane, dichloromethane (DCM), ethyl acetate (EtOAc), n-butanol (n-BuOH), and water were successively used to fractionate the crude extract into different portions. Various biological activities were performed on the crude extract, fractions, and some experiments on pure compounds. The bioassays were as follows: antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhi (using microplate alamar blue assay; MABA), antifungal activity against Aspergillus niger, A. fumigatus, Candida albicans, C. glabarate, Fusarium lini, Microspurum canis, and Trichophyton rubrum (using agar tube dilution method), antileishmanial activity against Leishmania major and L. tropica using a 96-well serial dilution protocol, anti-inflammatory activity using the respiratory burst assay, cytotoxicity against HeLa (cervical cancer) and BJ (normal fibroblast) cells using MTT assay, insecticidal activity against Tribolium castaneum, Sitophilus oryzae, and Rhyzopertha dominica (using the contact toxicity method), larvicidal activity against Aedes aegypti, anti-DPPH • activity, and cytotoxicity against brine shrimp (Artemia salina) in a lethality assay. Eventually, the phytochemicals from the active fractions were studied by gas chromatography coupled with mass spectrometry (GC-MS)., Results: Interestingly, the DCM fraction was the most active, followed by the n-hexane fraction in the biological assays, including antibacterial (>80% inhibition), leishmanicidal (IC 50 (L.major)  = 29.4 μg/mL, and IC 50 (L.tropica)  = 30.0 μg/mL), anti-inflammatory (IC 50  = 15.8 μg/mL), insecticidal (>80% inhibition), and larvicidal (100% inhibition of A. aegypti) assays. Further GC-MS analysis of the DCM and n-hexane fractions resulted in the characterization of 12 and 14 phytoconstituents, respectively, compared with the NIST library. Thymol and carvacrol were abundant in both fractions. To lesser quantities, the presence of monoterpenoids (p-cymen-8-ol, thymoquinone, 3-hydroxy-β-damascone, and 3-hydroxy-7,8-dihydro-β-ionol), phenylpropanoids (methoxyeugenol, elemicin, and 4-[(1E)-3-hydroxy-1-propenyl]-2-methoxyphanol, simple phenolics (salicylic acid and 4-methoxy-2,3,6-trimethyl-phenol), and a coumarin (6,7-dimethoxy-coumarin) were detected in the DCM fraction. On the other hand, besides a coumarin and monoterpenoids, the fatty acids (tetradecanoid acid, n-hexadecanoic acid, and linolenic acid) and a sesquiterpene (spathulenol) were observed in the n-hexane fraction. The EtOAc fraction scavenged the DPPH • radicals better than other fractions (IC 50  = 41.4 μg/mL), while in brine shrimp lethality assay, the crude extract was more active than n-hexane and DCM fractions with LD 50  = 385.20, 660.28, and 699.74 μg/mL, respectively. Surprisingly, the crude extract and fractions were ineffective against assayed fungal strains and tested cancer and non-cancer cell lines., Conclusions: Our findings showed that O. decumbens deserves to be a multi-bioactive medicinal plant, besides its ability for cereal protection against pests. To understand the principal mechanism of action, in silico, in vitro, and in vivo experiments may clarify the ambiguities and even figure out the synergistic behavior of the minor secondary metabolites., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cannabidiol (CBD), a cannabinoid that does not create psychoactive activities, has been identified as having a multitude of therapeutic benefits. This study delves into the chemical properties, pharmacokinetics, safety and toxicity, pharmacological effects, and most importantly, the association between the therapeutic potential of CBD and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. The relationship between Nrf2 and CBD is closely linked to certain proteins that are associated with cardiovascular dysfunctions, cancers, and neurodegenerative conditions. Specifically, Nrf2 is connected to the initiation and progression of diverse health issues, including nephrotoxicity, bladder-related diseases, oral mucositis, cancers, obesity, myocardial injury and angiogenesis, skin-related inflammations, psychotic disorders, neuropathic pain, Huntington's disease, Alzheimer's disease, Parkinson's disease, neuroinflammation, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis. The association between CBD and Nrf2 is a zone of great interest in the medical field, as it has the potential to significantly impact the treatment and prevention of wide-ranging health conditions. Additional investigation is necessary to entirely apprehend the mechanisms underlying this crucial interplay and to develop effective therapeutic interventions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Polyamines have received a lot of attention since the 1990s because of their anti-aging, anti-chronic disease, and proliferative effects. Wheat germ was reported as one of the natural sources of high polyamine, especially spermidine. The current study used three types of wheat germ: group A was industrially separated germ from whole grain, group B was the commercially available germinated wheat germ, and group C was manually separated wheat germ from germinated grain. The polyamine content of putrescine, spermidine, and spermine has been determined using a simplified isocratic LC-MS/MS method. An optimized extraction procedure was performed on all seven samples for obtaining a polyamine-enriched extract. The three dominant carbomylated polyamines were identified by analyzing the extracted samples in order to determine their relative abundance. Wheat germ powders contain the highest amount of polyamines (220-337 μg/g) of which spermidine is one of the most important. Germinated wheat grains, on the other hand, contain the least amount of this polyamine. The commercially available separated wheat germs are suggested as a good nutrition source of these polyamines., Competing Interests: The authors have no conflicts of interest to declare. All co‐authors have seen and agree with the contents of manuscript and there is no financial interest to report. We certify that the submission is original work and is not under review at any other publication., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Autism spectrum disorder (ASD) is among the most widespread neurodevelopmental diseases, with an approximate prevalence rate of 1 in 59. From a genetic point of view, this disorder is highly heterogeneous. This disorder is associated with both inheritable and de novo mutations in several genes. In addition to genetic loci that are identified through early karyotype analyses, recent advent of high throughput sequencing methods has facilitated identification of several genetic loci that confer risk of ASD. The current review provides an overview of different types of identified mutations including missense and nonsense mutations and copy number variations in various genes in individuals affected with ASD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Long intergenic non-protein coding RNA 472 (LINC00472) has been shown to regulate diverse cellular functions and contribute to the etiology of human disorders. LINC00472 gene is located on 6q13 and has different alternatively spliced transcripts. Expression pattern and function of LINC00472 have been evaluated in different types of cancers and some other disorders, including atherosclerosis, sepsis-induced acute hepatic injury, atrial fibrillation, neuropathic pain, primary biliary cholangitis and sepsis-induced cardiac dysfunction. This lincRNA can serve as a sponge for miR-24-3p, miR-196b-5p, miR-23a-3p, miR-93-5p, miR-4311, miR-455-3p and a number of other miRNAs. LINC00472 is able to regulate several pathways, including MEK/ERK, NF-kB, PTEN/PI3K/AKT, and STAT3 signaling pathways. This raises some concerning aspects that need to be investigated further and clarified in relation to diseases. Increasing our understanding of LINC00472's crucial roles will open new doors for creating effective therapeutic approaches against cancer and related diseases. The current study aims at providing an overview of functions of LINC00472 in malignant and non-malignant disorders., Competing Interests: Declaration of Competing Interest No conflicts of interest exist., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Small nucleolar RNA host gene 8 (SNHG8) is a long non-coding RNA that has physiological roles in epithelial and muscle satellite cells. This lncRNA has been reported to be over-expressed in a variety of cancer cell lines. Its silencing has attenuated tumor growth in animal models of cancers. SNHG8 can be served as a molecular sponge for some miRNAs to regulate their target genes. miR-634/ZBTB20, miR-335-5p/PYGO2, miR588/ATG7, miR-152/c-MET, miR-1270/BACH1, miR-491/PDGFRA, miR-512-5p/TRIM28, miR-149-5p/PPM1F, miR-542-3p/CCND1/CDK6, miR-656-3p/SERBP1, miR-656-3p/SATB1, miR-1270/S100A11 and miR-384/HOXB7 are examples of molecular axes being regulated by SNHG8 in the context of cancer. Moreover, it can affect pathogenesis of atherosclerosis, chronic cerebral ischemia, acute gouty arthritis, ischemic stroke and myocardial infarction through modulation of a number of molecular axes such as SNHG8/miR-384/Hoxa13/FAM3A and miR-335/RASA1 as well as NF-κB signaling pathway. The current review aims at summarization of the role of SNHG8 in diverse human disorders., Competing Interests: Conflict of interest The authors declare they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Polyamines prolong longevity due to their role in cell proliferation and are regarded as an essential group of anti-aging substances that reduce the risk of cardiovascular, neurological, and chronic inflammatory illnesses, as well as cancer. Because of its importance in growth and tissue regeneration, discovering polyamine-rich sources has gotten a lot of interest. Given the role of polyamines in controlling plant growth and physiological changes in the spring after cold winter stress, high polyamine concentrations in quickly growing plant tissues such as flowers, blossoms, and germs are possible. Based on this premise, five different spring flowers were selected and isolated from relevant plants, dried, and then quantified for the first time using an accurate, simple, and repeatable quantification method, liquid chromatography-tandem mass spectrometry. According to the amount of spermidine found in the samples investigated in this study, dried flower powders of Wisteria sinensis (244.18 µg/g), Lonicera caprifolium (217.28 µg/g), and Jasminum officinale (200.33 µg/g) appear to be a good source of spermidine. With additional research, W. sinensis dried flower powder is a good source of polyamines, whereas L. caprifolium and J. officinale dried flower powders are recommended as a rich source of spermidine for the preparation of natural supplements for people over the age of 30 to improve cell proliferation and anti-aging., Competing Interests: The authors declare that they do not have any conflict of interest and that the study does not involve any human or animal testing., (Copyright © 2023, Mohajeri et al.)

Long Intergenic Non-Protein Coding RNA 511 (LINC00511) is an RNA gene being mostly associated with lung cancer. Further assessments have shown dysregulation of this lncRNA in a variety of cancers. LINC00511 has interactions with hsa-miR-29b-3p, hsa-miR-765, hsa-mir-150, miR-1231, TFAP2A-AS2, hsa-miR-185-3p, hsa-miR-29b-1-5p, hsa-miR-29c-3p, RAD51-AS1 and EZH2. A number of transcription factors have been identified that regulate expression of LINC00511. The current narrative review summarizes the role of LINC00511 in different cancers with an especial focus on its prognostic impact in human cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ghafouri-Fard, Safarzadeh, Hussen, Taheri and Ayatollahi.)

The impact of Algae supplements and its extract on blood pressure has not concluded yet. The aim of this systematic review meta-analysis is to evaluate the antihypertensive activity of this group marine organism on human. Alga was used in some studies as capsules (from 500-mg to 8-g) and the follow-up duration changed from 17 days to 9 months. The difference in standardized mean and its corresponding 95% confidence interval (CI) was applied as the effect size of algae supplementation on systolic and diastolic blood pressure. Based on the results, a meta-analysis of 10 studies with baseline effect control demonstrated that there was no difference in the mean systolic blood pressure in the 2 groups SMD (95%CI): -1.05 (-2.85,0.76), but a significant difference in the mean diastolic blood pressure was observed and showed that the mean diastolic blood pressure in the treatment group was lower than the control group SMD(95%CI): -2.23 (-4.35,-0.11). A meta-analysis of 4 studies with no baseline control effect did not show significant results on both blood pressure. The evidence to support this systematic review meta-analysis requires more investigation and future large scale RCT clinical trial to confirm the results., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Slow-burning inflammation at the lesion rim is connected to the expansion of chronic multiple sclerosis (MS) lesions. However, the underlying processes causing expansion are not clearly realized. In this context, the current study used a bioinformatics approach to identify the expression profiles and related lncRNA-associated ceRNA regulatory axes in the periplaque region in MS patients. Expression data (GSE52139) from periplaque regions in the secondary progressive MS spinal cord and controls were downloaded from the Gene Expression Omnibus database (GEO), which has details on mRNAs and lncRNAs. Using the R software's limma package, the differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were found. The RNA interactions were also found using the DIANA-LncBase, miRTarBase, and HMDD databases. The Pearson correlation coefficient was used to determine whether there were any positive correlations between DEmRNAs and DElncRNAs in the ceRNA network. Finally, lncRNA-associated ceRNA axes were created based on co-expression and connections between DElncRNA, miRNA, and DEmRNA. We used the Enrichr tool to enrich the biological process, molecular function, and pathways for DEmRNAs and DElncRNAs. A network of DEmRNAs' protein-protein interactions was developed, and the top five hub genes were found using Cytoscape and STRING. The current study indicates that 15 DEmRNAs, including FOS , GJA1 , NTRK2 , CTNND1 , and SP3 , are connected to the MS ceRNA network. Additionally, four DElncRNAs (such as TUG1 , ASB16-AS1 , and LINC01094 ) that regulated the aforementioned mRNAs by sponging 14 MS-related miRNAs (e.g., hsa-miR-145-5p , hsa-miR-200a-3p , hsa-miR-20a-5p , hsa-miR-22-3p , hsa-miR-23a-3p , hsa-miR-27a-3p , hsa-miR-29b-3p , hsa-miR-29c-3p , hsa-miR-34a-5p ) were found. In addition, the analysis of pathway enrichment revealed that DEmRNAs were enriched in the pathways for the "MAPK signaling pathway", "Kaposi sarcoma-associated herpesvirus infection", "Human immunodeficiency virus one infection", "Lipid and atherosclerosis", and "Amphetamine addiction". Even though the function of these ceRNA axes needs to be investigated further, this study provides research targets for studying ceRNA-mediated molecular mechanisms related to periplaque demyelination in MS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sabaie, Khorami Rouz, Kouchakali, Heydarzadeh, Asadi, Sharifi-Bonab, Hussen, Taheri, Ayatollahi and Rezazadeh.)

The PI3K/AKT signaling has crucial role in the regulation of numerous physiological functions through activation of downstream effectors and modulation of cell cycle transition, growth and proliferation. This pathway participates in the pathogenesis of several human disorders such as heart diseases through regulation of size and survival of cardiomyocytes, angiogenic processes as well as inflammatory responses. Moreover, PI3K/AKT pathway participates in the process of myocardial injury induced by a number of substances such as H 2 O 2 , Mercury, lipopolysaccharides, adriamycin, doxorubicin and epirubicin. In this review, we describe the contribution of this pathway in the pathoetiology of myocardial ischemia/reperfusion injury and myocardial infarction, heart failure, cardiac hypertrophy, cardiomyopathy and toxins-induced cardiac injury., (© 2022. The Author(s).)

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural phenol that is present in the skin of the grape, blueberry, raspberry, mulberry, and peanut. This substance is synthesized in these plants following injury or exposure to pathogens. Resveratrol is used as a dietary supplement for a long time and its effects have been assessed in animal models of human disorders. It has potential beneficial effects in diverse pathological conditions such as diabetes mellitus, obesity, hypertension, neoplastic conditions, Alzheimer's disease, and cardiovascular disorders. Notably, resveratrol has been found to affect the expression of several genes including cytokine coding genes, caspases, matrix metalloproteinases, adhesion molecules, and growth factors. Moreover, it can modulate the activity of several signaling pathways such as PI3K/AKT, Wnt, NF-κB, and Notch pathways. In the current review, we summarize the results of studies that reported modulatory effects of resveratrol on the expression of genes and the activity of signaling pathways. We explain these results in two distinct sections of non-neoplastic and neoplastic conditions., (© 2022. The Author(s).)

Background: Recent studies on Leishmaniasis treatment have confirmed the antiparasitic effects of flavonols and organic antimony pentavalent [(Sb(V)] complexes., Objectives: This study aimed to identify new Sb(V) complexes by combining the benefits of antimonials and flavonols as well as by optimizing their properties., Methods: Kaempferol and quercetin peracetate were prepared using acetic anhydride in pyridine. By performing regioselective synthesis, 7-O-paramethylbenzyl as an electron-donating group and 7-O-paranitrobenzyl as an electron-withdrawing group were added to quercetin, and, then, the synthesis of Sb(V) kaempferol and quercetin derivative complexes were performed using SbCl 5 solution in glacial acetic acid. The structures were confirmed by UV, ESI mass, IR, 1H-, and 13 C-NMR spectral data, and the Stoichiometry of the ligand-metal complex by the mole ratio method. Computational molecular modeling was conducted using the Gaussian program., Results: The structures were confirmed based on the results from UV, nuclear magnetic resonance (NMR), and electrospray ionization (ESI) mass analyses (3-12). Among the produced compounds, 11 and 12 as newly described, and other compounds as pre-defined compounds were identified. According to the results from biological test, kaempferol triacetate with more lipophilicity showed the highest anti-promastigote activity with an IC 50 value of 14.93 ± 2.21 µM. As for anti-amastigote activity, despite the differences, all antimony complexes showed anti-amastigote effects in vitro with IC 50 values of 0.52 to 14.50 µM., Conclusions: All flavonol Sb(V) complexes showed higher activity compared to meglumine antimonate in anti-amastigote effect. Inside the host macrophages, by breaking down the complex into antimony and quercetin or kaempferol analogs, the observed antiparasitic effects may have been related to both Sb(V)/Sb(III) conversion and flavonoid antileishmanial activities., Competing Interests: Conflict of Interests: The authors have no conflict of interests, but SMA and MG as editorial board members have conflict of interests., (Copyright © 2022, Author(s).)

Propolis, a resinous substance produced by honeybees from various plant sources, has been used for thousands of years in traditional medicine for several purposes all over the world. The precise composition of propolis varies according to plant source, seasons harvesting, geography, type of bee flora, climate changes, and honeybee species at the site of collection. This apiary product has broad clinical applications such as antioxidant, anti-inflammatory, antimicrobial, anticancer, analgesic, antidepressant, and anxiolytic as well asimmunomodulatory effects. It is also well known from traditional uses in treating purulent disorders, improving the wound healing, and alleviating many of the related discomforts. Even if its use was already widespread since ancient times, after the First and Second World War, it has grown even more as well as the studies to identify its chemical and pharmacological features, allowing to discriminate the qualities of propolis in terms of the chemical profile and relative biological activity based on the geographic place of origin. Recently, several in vitro and in vivo studies have been carried out and new insights into the pharmaceutical prospects of this bee product in the management of different disorders, have been highlighted. Specifically, the available literature confirms the efficacy of propolis and its bioactive compounds in the reduction of cancer progression, inhibition of bacterial and viral infections as well as mitigation of parasitic-related symptoms, paving the way to the use of propolis as an alternative approach to improve the human health. However, a more conscious use of propolis in terms of standardized extracts as well as new clinical studies are needed to substantiate these health claims., (© 2022. The Author(s).)

Background: Rosa canina has been traditionally known as a medicinal plant. Different applications of fruits (Rose hip) comprise the food, perfume, and cosmetic industries., Objectives: This study aimed to prepare an enriched polyphenolic fraction from Rosa canina in addition to its biological activities., Methods: Poly phenolic enriched fraction was prepared using Amberlite XAD-7 for removing unwanted components. Phenols, flavonoids, and anthocyanins content analyses showed that they increased significantly compared to the extract. HPLC analysis showed that this fraction is a rich source of ascorbic acid., Results: The results of the DPPH, ferric-reducing antioxidant power (FRAP), ABTS, and nitric oxide assay confirmed that the antioxidant activities of the fraction had been increased compared to the extract. The oxygen radical absorbance capacity (ORAC) assay and cellular antioxidant activity of the fraction also confirmed its potential antioxidant activity. This fraction showed xanthine oxidase inhibitory activity at 100 µg/mL concentration. Comet assay analysis revealed that this fraction at 25 - 100 µg/mL concentrations inhibited H 2 O 2 genotoxicity in human lymphocytes., Conclutions: This study suggests that the fruit of Rosa canina could be considered as a potential antioxidant, a xanthine oxidase inhibitor, and an antigenotoxic source, and the application of Amberlite XAD-7 improves extraction efficiencies through enrichment of phenolic compounds in this plant., Competing Interests: Conflict of Interests: No conflict of interests is declared by the authors., (Copyright © 2022, Author(s).)

Circular RNAs are a group of ancient but recently appreciated transcripts that affect carcinogenesis. An example of cancer-related circular RNAs is circ&#95;CDR1as. It is mostly regarded as an oncogenic circular RNA, yet in bladder cancer and glioma it has the opposite effect. In gastric and ovarian cancer, both roles have been reported for this circular RNA. Circ&#95;CDR1as has regulatory effects on miR-1270/AFP, miR-1287/Raf1, miR-7-5p/KLF4, miR-641/HOXA9, miR-219a-5p/SOX5, miR-7/HOXB13 and miR-876-5p/MAGE-A molecular axes. miR-7 is the most appreciated interacting miRNA with circ&#95;CDR1as, since its interaction with circ&#95;CDR1as has been validated in liver cancer, lung cancer, colorectal cancer, esophageal carcinoma, gastric cancer, pancreatic cancer, thyroid cancer, oral squamous cell carcinoma, nasopharyngeal carcinoma and osteosarcoma. The present article aims at summarization of the role of circ&#95;CDR1as in neoplasms and its application as a biomarker in human cancers., (Copyright © 2022. Published by Elsevier GmbH.)

Anthraquinones are an interesting chemical class of polyketides since they not only exhibit a myriad of biological activities but also contribute to managing ecological roles. In this review article, we provide a current knowledge on the anthraquinoids reported from marine-derived fungi, isolated from various resources in both shallow waters such as mangrove plants and sediments of the mangrove habitat, coral reef, algae, sponges, and deep sea. This review also tentatively categorizes anthraquinone metabolites from the simplest to the most complicated scaffolds such as conjugated xanthone-anthraquinone derivatives and bianthraquinones, which have been isolated from marine-derived fungi , especially from the genera Apergillus , Penicillium , Eurotium , Altenaria , Fusarium , Stemphylium , Trichoderma , Acremonium , and other fungal strains. The present review, covering a range from 2000 to 2021, was elaborated through a comprehensive literature search using the following databases: ACS publications, Elsevier, Taylor and Francis, Wiley Online Library, MDPI, Springer, and Thieme. Thereupon, we have summarized and categorized 296 anthraquinones and their derivatives, some of which showed a variety of biological properties such as enzyme inhibition, antibacterial, antifungal, antiviral, antitubercular (against Mycobacterium tuberculosis ), cytotoxic, anti-inflammatory, antifouling, and antioxidant activities. In addition, proposed biogenetic pathways of some anthraquinone derivatives are also discussed.

Ginsenosides belong to a group of steroid glycosides that are extracted from the plant genus Panax (ginseng). This plant has been used for a long time for the treatment of a variety of disorders in traditional medicine. Recent studies have assessed the biological impact of Ginsenosides in cell culture or animal models. Animal studies have shown their beneficial impacts in the remedy of pathological conditions in different tissues. The ameliorating effects of Ginsenosides in diverse pathogenic conditions can be attributed to their effects on the production of reactive oxygen species. These substances mainly affect the activity of AMPK/AKT and PI3K/AKT pathways. The beneficial effects of Ginsenosides have been appraised in diabetes-related complications, spinal cord injury, cerebral ischemia, myocardial ischemia, and other disorders which are associated with oxidative stress. Moreover, these substances have been shown to interfere with the pathologic conditions during carcinogenesis. In the current study, we explain these impacts in two distinct sections including non-neoplastic conditions and neoplastic conditions., (© 2022. The Author(s).)

Background: Candida albicans cause oral and vaginal mucosa infections as well as bloodstream and deep-tissue infections. Commonly, clotrimazole as a broad-spectrum antimitotic drug applied for treatment of Candida albicans infections. Bacterial ghosts are dead cells that have the broad potential to target the various body tissues and cells as drug vector., Objectives: We hope to conquest this resistance by using clotrimazole loaded on bacterial ghosts., Methods: Lactobacillus ghosts were produced by using tween 80 and lactic acid according to the protocol and the amount of the DNA and protein in supernatant was measured by Nano-drop spectrophotometry. Ghost's morphological characteristics were detected by using light microscopy, SEM and AFM. Antifungal activities of the synthesized ghosts were measured by plate methods. Three independent vertical Franz cells were used to evaluate drug release profile. BG-clotrimazole was added into cream base and was examined for dispensability as well as uniformity of the formulation on the skin., Results: Results of the Nano-drop analysis showed that protein and DNA was seen in supernatant of treatment compared to control groups. AFM results showed well-dispersed and rod-shaped L. casei ghost cells. Lysis pores formation in the L. casei ghosts was indicated by SEM micrographs. BGs represent an excellent drug delivery system because of the high loading capability. Nearly, 50% of clotrimazole was released from BGs during 90 min. Highest anticandidal activity occurred using 100 mg/l clotrimazole-BG, while toxic effects were also seen with 10 mg/l clotrimazole. IC 50 clotrimazole-BG was found at 0.001 mg/l. Chemical stability results showed that about 90% of clotrimazole remained in the formulation., Conclusion: It could be concluded that the bacterial ghosts are very talented to high loading capability, keeping and releasing drug during six months, therefore these could act as an excellent drug delivery system., (© 2022. Springer Nature Switzerland AG.)

Curcumin is a natural polyphenol with antioxidant, antibacterial, anti-cancer, and anti-inflammation effects. This substance has been shown to affect the activity of Nrf2 signaling, a pathway that is activated in response to stress and decreases levels of reactive oxygen species and electrophilic substances. Nrf2-related effects of curcumin have been investigated in different contexts, including gastrointestinal disorders, ischemia-reperfusion injury, diabetes mellitus, nervous system diseases, renal diseases, pulmonary diseases, cardiovascular diseases as well as cancers. In the current review, we discuss the Nrf2-mediated therapeutic effects of curcumin in these conditions. The data reviewed in the current manuscript indicates curcumin as a potential activator of Nrf2 and a therapeutic substance for the protection of cells in several pathological conditions.

Gastric cancer (GC) is one of the most commonly diagnosed neoplasms in the world. A number of environmental and lifestyle factors, particularly chronic infection with Helicobacter pylori, have been found to partake in the pathogenesis of GC. The advent of high-throughput genome and transcriptome analysis has enhanced the knowledge about molecular mechanisms of the pathogenesis of GC. However, data regarding the expression of several circRNAs, such as circLMTK2, are not consistent. We explain the role of circRNAs in the development of GC. We searched databases for the newest publications using the terms gastric cancer and circRNA. Each circRNA alteration, downstream targets, its impacts on cancer cells, and the prognostic and diagnostic roles of these circRNAs have been discussed. Taken together, circRNAs can be putative biomarkers in GC and potential targets for the treatment of this cancer. Yet, this field is still in its infancy and needs further experiments for reaching the clinical application. As these transcripts are stable in circulation, they can be used in non-invasive methods of cancer detection and patients' follow-up., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Paclitaxel is a broad-spectrum anticancer compound, which was derived mainly from a medicinal plant, in particular, from the bark of the yew tree Taxus brevifolia Nutt. It is a representative of a class of diterpene taxanes, which are nowadays used as the most common chemotherapeutic agent against many forms of cancer. It possesses scientifically proven anticancer activity against, e.g., ovarian, lung, and breast cancers. The application of this compound is difficult because of limited solubility, recrystalization upon dilution, and cosolvent-induced toxicity. In these cases, nanotechnology and nanoparticles provide certain advantages such as increased drug half-life, lowered toxicity, and specific and selective delivery over free drugs. Nanodrugs possess the capability to buildup in the tissue which might be linked to enhanced permeability and retention as well as enhanced antitumour influence possessing minimal toxicity in normal tissues. This article presents information about paclitaxel, its chemical structure, formulations, mechanism of action, and toxicity. Attention is drawn on nanotechnology, the usefulness of nanoparticles containing paclitaxel, its opportunities, and also future perspective. This review article is aimed at summarizing the current state of continuous pharmaceutical development and employment of nanotechnology in the enhancement of the pharmacokinetic and pharmacodynamic features of paclitaxel as a chemotherapeutic agent., Competing Interests: The authors report no declarations of interest., (Copyright © 2021 Javad Sharifi-Rad et al.)

Treatment of cancer in young adults is associated with several side effects, particularly in the reproductive system. Detrimental effects of chemotherapy on the germ cells depend on many factors including primary semen parameters, the way of drug administration, the kind and dose of chemotherapeutic regimens, and the phase of spermatogenesis during the time of drug administration. Lack of appropriate fertility preservation treatments particularly in the affected children necessitates the introduction of methods to amend the harmful effects of chemotherapeutic agents on male germ cells. Several studies have assessed the toxic effects of chemotherapeutic agents in rodent models and tested a number of antioxidants to evaluate their possible impact on the preservation of sperm cells. In the present manuscript, we describe the effects of the mostly investigated chemotherapeutic drugs in this regard i.e., cisplatin, doxorubicin, paclitaxel, 5-fluorouracil, and cyclophosphamide. As several in vivo and in vitro studies have shown the impact of antioxidants on chemotherapy-induced damage of sperms, we also describe the protective effects of antioxidants in this regard., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The genus Diplazium (family: Athyriaceae) comprises approximately 350 species of pteridophytes . Diplazium esculentum (Retz.) Sw. is an important member of this genus and commonly known as a wild vegetable in the Himalayan and sub-Himalayan communities. According to the literature analysis, D. esculentum was traditionally used for the prevention or treatment of several diseases such as diabetes, smallpox, asthma, diarrhea, rheumatism, dysentery, headache, fever, wounds, pain, measles, hypertension, constipation, oligospermia, bone fracture, and glandular swellings. Various extracts of D. esculentum were evaluated to elucidate their phytochemical and pharmacological activities. A wide array of pharmacological properties such as antioxidant, antimicrobial, antidiabetic, immunomodulatory, CNS stimulant, and antianaphylactic activities have been recognized in different parts of D. esculentum . The review covers a systematic examination of pharmacognosy, phytochemistry, and pharmacological applications of D. esculentum , but scientifically, it is not fully assessed regarding complete therapeutic effects, toxicity, and safety in the human body. The published literature on D. esculentum and its therapeutic properties were collected from different search engines including Wiley online, PubMed, Springer Link, Scopus, Science Direct, Web of Science, Google Scholar, and ACS publications by using specific terms such as " Diplazium esculentum, bioactive compounds, biological activities and health benefits" from 1984 to 2021 (March). Therefore, further studies are required to identify the detailed action mechanism of D. esculentum in vitro/in vivo , and also, more studies should focus on conservation, cultivation, and sustainable utilization of the species., Competing Interests: The authors declared that they have no conflict of interest regarding this manuscript., (Copyright © 2021 Prabhakar Semwal et al.)

Quercetin is a flavonoid existing in different herbs, fruits, seeds, nuts and tea. It has beneficial effects on human health through mediating antioxidant activities, immune-modulatory impacts and regulating metabolic pathways. These effects are most probably induced through modulation of activity of signaling pathways and expression of genes. Several in vitro studies have verified anti-proliferative effects of quercetin and its effect on expression of apoptotic genes and cell cycle-related genes. Moreover, through modulation of a number of proteins such as NF-kB, PARP, STAT3, Bax, Bcl-2, COX2, and cytokines, quercetin has beneficial effects in neurodegenerative disorders, liver diseases and diabetes. PI3K/AKT is the mostly linked pathway with beneficial effects of quercetin. In the current manuscript, we explain the impact of quercetin on expression of genes and function of cellular signaling cascades in different contexts., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Prostate cancer is one of the common cancers with a high mortality rate in men. Therefore, there is always a necessity to discover new medications for treatment or alleviating its symptoms. In recent years, anticancer properties of a number of delphinium species were reported, but there is no study on the anticancer effects of Delphinium semibarbatum ( D. semibarbatum ) alkaloid contents. Therefore, this survey aimed to check the cytotoxicity and apoptotic properties of D. semibarbatum alkaloid fractions (DSAFs) against prostate cancer cells. Cytotoxicity was measured by MTT assay. We examined the apoptosis by detecting annexin V-FITC/PI staining, the mitochondrial membrane potential (ΔΨm) disruption, reactive oxygen species (ROS) generation, the activity of caspase-3, and expression of the Bax and Bcl-2 in cancer cells. DSAFs treatment inhibited the growth of LNCaP and DU-145 cells by the increase of apoptotic (Q2+Q3) cells detected by annexin V/PI assay. We found over-generation of intracellular ROS and ΔΨm loss in mitochondrial membrane potential treated cell lines. Attenuation of anti-apoptotic Bcl-2 followed by the increase in pro-apoptotic Bax bands, as well as activation of the caspase-3 enzyme was shown in Western blot analysis. Phytochemical analysis suggested that hetisine type diterpene alkaloids were probably responsible for apoptotic activities. Conclusively, the present study demonstrated that D. semibarbatum alkaloid content exerted antiproliferative effects against prostate cancer cells by inducing the intrinsic pathway of apoptosis.

Cardiovascular diseases (CVD) are one of the main causes of mortality in the world. The development of these diseases has a specific factor-alteration in blood platelet activation. It has been shown that phenolic compounds have antiplatelet aggregation abilities and a positive impact in the management of CVD, exerting prominent antioxidant, anti-inflammatory, antitumor, cardioprotective, antihyperglycemic, and antimicrobial effects. Thus, this review is intended to address the antiplatelet activity of phenolic compounds with special emphasis in preventing CVD, along with the mechanisms of action through which they are able to prevent and treat CVD. In vitro and in vivo studies have shown beneficial effects of phenolic compound-rich plant extracts and isolated compounds against CVD, despite that the scientific literature available on the antiplatelet aggregation ability of phenolic compounds in vivo is scarce. Thus, despite the current advances, further studies are needed to confirm the cardioprotective potential of phenolic compounds towards their use alone or in combination with conventional drugs for effective therapeutic interventions., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Javad Sharifi-Rad et al.)

Circular RNAs (cirRNAs) are generally considered as non-coding RNAs which can act as molecular sponges for miRNAs, exert regulatory roles in transcription or splicing, and interplay with RNA binding proteins. These single-stranded transcripts can affect tumor growth, the metastatic ability of cancer cells, stemness properties, and resistance to therapeutic options. Recent investigations have shown the crucial effects of circrNAs in the evolution of breast cancer. Signature of circRNAs in breast cancer samples has been mostly assessed through microarray-based methods revealing up-regulation of some circRNAs such as circ-TFF1, circACAP2, circ-TFCP2L1, hsa&#95;circ&#95;0000519, circDENND4C, circPLK1 and circRNA&#95;069718, while down-regulation of other circRNAs such as hsa&#95;circ&#95;0000375, circYap, hsa&#95;circ&#95;0025202, circTADA2A-E6, circASS1 and circRNA&#95;BARD1 in breast cancer samples. Mechanistically, these transcripts mainly affect breast cancer tumorigenesis via serving as sponges for miRNAs. In the current manuscript, we explore the results of researches that appraised the role of circRNAs in breast cancer., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

The current coronavirus disease (COVID-19) outbreak is a significant threat to human health and the worldwide economy. Coronaviruses cause a variety of diseases, such as pneumonia-like upper respiratory tract illnesses, gastroenteritis, encephalitis, multiple organ failure involving lungs and kidneys which might cause death. Since the pandemic started there have been more than 107 million COVID-19 infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ∼2.4 million deaths globally. SARS-CoV-2 is easily transmitted from person-to-person and has spread quickly across all continents. With the continued increase in morbidity and mortality caused by COVID-19, and the damage to the global economy, there is an urgent need for effective prevention and treatment strategies. The advent of safe and effective vaccines has been a significant step forward in the battle against COVID-19, however treatment of the symptoms associated with the disease still requires new anti-viral and anti-inflammatory drug therapies. To this end, scientists have been investigating available natural products that may be effective against SARS-CoV-2, with some products showing promise in fighting several viral infections. Since many natural products are dietary components or are prepared as dietary supplements people tend to consider them safer than synthetic drugs. For example, Traditional Chinese Medicines have been effectively utilized to treat SARS-CoV-2 infected patients with promising results. In this review, we summarize the current knowledge of COVID-19 therapies and the therapeutic potential of medicinal plant extracts and natural compounds for the treatment of several viral infections, with special emphasis on SARS-CoV-2 infection. Realistic strategies that can be employed for the effective use of bioactive compounds for anti-SARS-CoV-2 research are also provided., Competing Interests: The authors declare that the paper was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ayatollahi, Sharifi-Rad, Tsouh Fokou, Mahady, Ansar Rasul Suleria, Krishna Kapuganti, Gadhave, Giri, Garg, Sharma, Ribeiro, Rodrigues, Reiner, Taheri and Cruz-Martins.)

Two novel fluorescent peptide-based chemosensors, including A (2-amino-benzoyl-Ser-Glu-Glu-NH 2 ) and B (2-amino-benzoyl-Ala-Glu-Pro-Glu-Ala-Glu-Pro-NH 2 ) were synthesized and characterized by nuclear magnetic resonance (NMR) spectra. These fluorescent probes exhibited excellent selective and sensitive responses to Al 3+ ions over other metal ions in aqueous buffered solutions. The limits of detection for both chemosensors towards the Al 3+ ions were in the order of ∼10 -7  M (A: 155 nM and B: 195 nM), which clearly indicates that these probes have significant potential for biological applications. They also displayed high binding affinity (1.3029 × 10 4  M -1 and 1.7586 × 10 4  M -1 relevant to A and B respectively). These two chemosensors are great analytical probes that produce turn-on responses upon binding to Al 3+ ions through an intramolecular charge transfer (ICT) mechanism. In addition, the application of both chemosensors was examined over a wide range of pH. The fluorescent peptide-based probes and Al 3+ form a 1:1 coordination complex according to the ESI-MS and Job's plot analysis. Notably, upon addition of Al 3+ to these chemosensors, a fluorescence enhancement of approximately 8-fold was observed and the binding mode was determined using NMR titration and fluorescence emission data.

Prosopis farcta (Banks & Sol.) J.F.Macbr. is an emerging medicinal plant containing a diverse array of phytochemicals, including protein, fat, carbohydrate, fibre, alkaloids, fatty acids, glycosides, and polyphenols, with strong antioxidant potential. However, the screening and characterization of phenolic compounds in P. farcta is limited. This study is conducted to determine the polyphenol contents and their antioxidant activity in P. farcta leaves samples via liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS) and high-performance liquid chromatography-photodiode array (HPLC-PDA). Total phenolic content (TPC), total flavonoid content (TFC), and total tannins content (TTC) were determined for polyphenol estimation. The antioxidant properties were measured by total antioxidant capacity (TAC), 2,2'-Diphenyl-2-picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Power (FRAP), and 2,2"²-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). LC-ESI-QTOF-MS/MS was used to identify and characterize 47 phenolic compounds, which mainly included phenolic acids (13), flavonoids (28), other polyphenols (4), lignans (1), and stilbenes (1). According to HPLC-PDA quantification, chlorogenic acid (9.78 ± 2.15 mg/g dw) was the most abundant phenolic acid, while the main flavonoids included catechin (12.73 ± 1.29 mg/g dw) and kaempferol (7.93 ± 1.47 mg/g dw). The study demonstrated the significance of P. farcta as a rich source of phenolic compounds with antioxidant capacity that can be widely used in food, beverage, feed, and pharmaceutical applications.

This study aimed to investigate the high-performance thin-layer chromatography (HPTLC) fingerprinting and in-vivo anti-inflammatory and antinociceptive activities of different leaf extracts (ethanolic extract, n-hexane, chloroform, and ethyl acetate) of Pyracantha coccinea M.Roem. plant. A total of one hundred and twenty-four Wistar rats for anti-inflammatory and antinociceptive tests (carrageenan and formalin tests, respectively) were treated with two doses of the ethanolic extract (100 and 300 mg/kg), two doses of other plant fractions (30 and 100 mg/kg), Diclofenac (25 mg/kg) as the positive control, and normal saline as the negative control group, by oral gavage route. HPTLC fingerprinting is used for assay of terpenoids, flavonoids, alkaloids, and antioxidant activity. Treatment of the animal with the ethanolic extract at doses of 100 and 300 mg/kg, both ethyl acetate and chloroform fractions at the dose of 30 mg/kg and 100 mg/kg decreased the pain score in the formalin test and paw edema caused by carrageenan relative to control group significantly. Moreover, these extracts reported the highest amounts of flavonoid contents. In conclusion, phytochemicals present in Pyracantha coccinea M.Roem. leaves have anti-inflammatory and antinociceptive activities. Future studies are needed to identify the compounds with the anti-inflammatory and antinociceptive potential present in the plant.

Tuberculosis is a highly infectious disease declared a global health emergency by the World Health Organization, with approximately one third of the world's population being latently infected with Mycobacterium tuberculosis. Tuberculosis treatment consists in an intensive phase and a continuation phase. Unfortunately, the appearance of multi drug-resistant tuberculosis, mainly due to low adherence to prescribed therapies or inefficient healthcare structures, requires at least 20 months of treatment with second-line, more toxic and less efficient drugs, i.e., capreomycin, kanamycin, amikacin and fluoroquinolones. Therefore, there exists an urgent need for discovery and development of new drugs to reduce the global burden of this disease, including the multi-drug-resistant tuberculosis. To this end, many plant species, as well as marine organisms and fungi have been and continue to be used in various traditional healing systems around the world to treat tuberculosis, thus representing a nearly unlimited source of active ingredients. Besides their antimycobacterial activity, natural products can be useful in adjuvant therapy to improve the efficacy of conventional antimycobacterial therapies, to decrease their adverse effects and to reverse mycobacterial multi-drug resistance due to the genetic plasticity and environmental adaptability of Mycobacterium. However, even if some natural products have still been investigated in preclinical and clinical studies, the validation of their efficacy and safety as antituberculosis agents is far from being reached, and, therefore, according to an evidence-based approach, more high-level randomized clinical trials are urgently needed., (Copyright © 2020. Published by Elsevier Inc.)

Cardiovascular diseases are a leading cause of worldwide death and excessive platelet is closely related with their pathogenesis. Different plants and natural compounds have demonstrated anti-platelet effects. The aim of this study was to report the high-performance thin-layer chromatography (HPTLC) fingerprinting and anti-platelet-aggregation activities of different leaf extracts (n-hexane, chloroform, ethyl acetate, methanol and aqueous) of Prosopis farcta (Syrian mesquite) plant. The results showed a 100% inhibition of aggregation activity after plasmatic adenosine diphosphate (ADP) aggregation activation of ethyl acetate, ethanolic, methanolic and aqueous extracts, at 60 mg/mL concentration. The IC50 ADP value of these extracts ranged between 4.07 and 11.39 mg/mL. Moreover, these extracts reported the highest amounts of phenolic and flavonoid contents. In conclusion, phytochemicals present in P. farcta leaves have anti-platelet-aggregation activities. Future studies are needed to identify the compounds with anti-platelet potential present in P. farcta.

Pyracantha spp. are commonly called firethorn, and attract human attention due to their colorful berries. These berries are eaten globally as a traditional remedy for treating different stomach abnormalities, and as a cooking ingredient for folk diets. The present review aims to provide an overview on Pyracantha genus' geographical distribution and botanical description, traditional uses, phytochemical composition, biological activities and safety issues. Several biological activities have been reported to Pyracantha species, namely antioxidant, anti-inflammatory, antimicrobial, larvicidal and cytotoxic properties, most of them attributed to the use of their fruits. Pyracantha species phytochemical composition reveal the presence of interesting bioactive molecules, such as pyracrenic acid and fortuneanosides. The currently reported biological activities to these plants derive from in vitro and in vivo studies, so that clinical trials are needed to confirm these preclinical results. Nonetheless, Pyracantha species can be suggested as a safe herb useful to develop future drug formulations and functional foods.

Phytol (PHY) is an acyclic natural diterpene alcohol and a chlorophyll constituent that exhibits several pharmacological effects, such as anticancer, antioxidant, and antimicrobial. Here, we aimed to assess the PHY anti-inflammatory effect in vitro and in vivo, and to deepen knowledge on the possible mechanism of action. For this purpose, egg albumin (in vitro) test was performed by using acetyl salicylic acid (ASA) as a standard nonsteroidal anti-inflammatory drugs (NSAID). For in vivo test, male Wistar albino rats were treated (intraperitoneally) with 100 mg/kg of PHY and/or standard NSAIDs ASA (100 mg/kg) and diclofenac sodium (Diclo-Na, 10 mg/kg) to evaluate the combined effect of PHY in formalin-induced paw edema model. Furthermore, an in silico (CADD) study was accomplished to assess the effect of PHY against cyclooxygenase (COX)-1 and 2 enzymes, nuclear factor kappa B (NF-κB), and interleukin-1β (IL-1β). Results revealed that PHY exhibits dose-dependent anti-inflammatory effect using the egg albumin method. PHY (100 mg/kg) co-treated with ASA and/or Diclo-Na reduced paw edema better than PHY alone or NSAIDs individual groups. Computational study showed that PHY efficiently interacts with COX-1 and 2, NF-κB, and IL-1β. In conclusion, PHY exhibits anti-inflammatory activity, possibly via COX-1 and 2, NF-κB, and IL-1β dependent pathways.

Alstonia sholaris is an evergreen tree commonly found in South East Asia. In traditional medicine pharmacological activities are attributed to the leaves and bark of this plant. The aim of this study is characterizing the chemicals present in A. sholaris leaves and bark extracts and study their antimicrobial activities. Solvent extractions with Soxhlet apparatus of leaves and bark were obtained using hexane, benzene, isopropanol, methanol, and water. The crude extracts were concentrated and screened for qualitative phytochemical analysis and thin layer chromatography, and the antibacterial, antifungal an antiviral activity of crude extracts were measured by in vitro methods. Isopropanol and methanol extracts showed significant antibacterial activity and it was more pronounced against Gram positive than against Gram negative bacteria. Hexane, benzene, isopropanol and methanol fractions of A. scholaris bark and leaf showed activity against Enterobacter cloacae. Isopropanol extract showed maximum activity against selected human pathogenic fungus. In conclusion, the leaves and bark of A. scholaris are rich in phytochemicals with antimicrobial activities against human pathogens, being the isopropanol fraction the one with the highest antibacterial, antifungal, antiviral and anti-mycobacterial activities.

Alstonia venenata is a plant commonly found in South India and used in traditional medicine. The aim of this study was to characterize the phytochemicals present in A. venenata leaf and bark extracts and study their antimicrobial activities. Solvent extractions with Soxhlet apparatus of leaves and bark were obtained using hexane, benzene, isopropanol, methanol, and water. The crude extracts were concentrated and screened for qualitative phytochemical content and analyzed by thin layer chromatography. The antibacterial, antifungal and antiviral activities of crude extracts were measured by in vitro methods. Alkaloids, carbohydrates, tannins, phenolic compounds, terpenoids, cardiac glycosides and amino acids were found in the different crude extracts analyzed. Isopropanol extracts showed antifungal activity and it was more pronounced in the bark extract than the leaf extract. Moreover, the isopropanol extract exhibited antibacterial and antiviral activity. In conclusion, the leaves and bark of A. venenata have antimicrobial components which are more present in the isopropanol fraction.

Telomere length is correlated with cell proliferation, and cancer cells are characterized by an uncontrolled cell cycle. Being apoptosis one of the checks and balances incorporated into cells cycle, due to its characteristics, cancer cells are able to overcome this process. In particular, the tumour suppressor protein p53 loss or inactivation can lead to activation of telomerase enzyme, which can make cells unable to detect DNA damages that spurs apoptosis. Some bioactive compounds, in particular phenolic compounds, saponins and alkaloids have revealed good abilities to affect p53 expression and indirectly control the telomere length. In this sense, this review gives a key emphasis to the ability of these compounds in blocking cancer progression by acting on p53 expression and controlling telomere length. As main findings, phenolic compounds, saponins and alkaloids interfere with cancer progression by stimulating p53 expression, which can cause pro-apoptotic onset and restrict the anti-apoptotic activity, in addition to preventing telomerase enzyme activity.