Protective effects of Rubus tereticaulis leaves ethanol extract on rats with ulcerative colitis and bio-guided isolation of its active compounds: A combined in silico, in vitro and in vivo study.

The aim of this study was to evaluate the therapeutic effect of active ethanol extract obtained from the leaves of Rubus tereticaulis (RTME) against colitis, and to purify major compounds from this extract by bioassay-directed isolation. Rats with colitis induced via intra-rectal acetic acid administration (5%, v/v) received RTME or sulfasalazine for three consecutive days. On day four, all rats were decapitated, and the colonic tissue samples were collected for macroscopic score, colon weight, reduced glutathione (GSH), myeloperoxidase (MPO), and malondialdehyde (MDA) analyses. The active compounds and chemical composition of RTME were determined by bio-guided isolation and LC-MS/MS, respectively. Compared to the colitis group, the rats treated with RTME displayed significantly lowered macroscopic scores and colon wet weights (p < 0.001). These effects were confirmed biochemically by a decrease in colonic MPO activity (p < 0.001), MDA levels (p < 0.001), and an increase in GSH levels (p < 0.001). Kaempferol-3-O-ß-d-glucuronide (RT1) and quercetin-3-O-ß-d-glucuronide (RT2) were found to be the major compounds of RTME, as evidenced by in vitro anti-inflammatory and antioxidant activity-guided isolation. Their anti-inflammatory/antioxidant activities were also predicted by docking simulations. Additionally, quinic acid, 5-caffeoylquinic acid, quercetin pentoside, quercetin glucoside, quercetin-3-O-ß-d-glucuronide, kaempferol-3-O-ß-d-glucuronide, and kaempferol rutinoside were identified in RTME via using LC-MS/MS. RT2, along with other compounds, may be responsible for the observed protective action of RTME against colitis. This study represents the first report on the beneficial effects of RTME in an experimental model of colitis and highlights the potential future use of RTME as a natural alternative to alleviate colitis.

An Ethnobotanical study of medicinal plants in Tasköprü (Kastamonu-Turkey).

This pharmaceutical ethnobotanical research was carried out in Tasköprü District in Kastamonu, in northern Anatolia. It assembles the elaborations of plants used as folk medicines, and the ethnopharmacological data collected in the course of in-person semi-structured interviews with an open-ended questionnaire. The study's aims were two-fold: gathering and identifying plants that the local inhabitants use therapeutically, and recording information related to traditional folk medicine (primarily for humans, and if extant for animals). The plants were gathered during several outings between May 2016 and July 2018. The organization of the data was based on the use-reports (UR) and was done according to the ICPC-2 classification. In addition, cultural importance index (CI) and informant consensus factor (FIC) calculations were made for the data collected. The research identified 101 plant taxa of 31 families used in folk medicine. Of these, 89 were wild and 12 were cultivated taxa. In total, 499 medicinal uses were determined. The CI values indicated that the most significant medicinal plant specimens were Pinus nigra subsp. pallasiana (0.78), P. sylvestris var. hamata (0.75) and Plantago lanceolata, P. major subsp. intermedia and P. major subsp. major (0.58 each). The most prevalent families were Asteraceae (2.14), Rosaceae (1.93), Pinaceae (1.81) and Plantaginaceae (1.74). Respiratory system (0.95), skin and subcutaneous tissue (0.94), nervous system (0.92) and circulatory system disorders (0.88) and ethnoveterinary uses (0.89) had the highest FIC values. The most frequently used preparation process was observed to be decoction (38.4%) and the most commonly utilized plant parts were aerial (21%). Along with recording 20 plant taxa as medicinal plants for the first time, this study documented a total of 303 new therapeutic uses. This study concludes with the finding that traditional knowledge of medicinal plants remains prevalent in Ta rticularly among its rural inhabitants.

The Clinical Significance of Vitamin D and Zinc Levels with Respect to Immune Response in COVID-19 Positive Children.

AIM: In this study, we aimed to evaluate serum vitamin D and zinc levels in children diagnosed with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: In this study, 88 children with COVID-19 disease and 88 healthy children aged 1-18 years were enrolled between 01 July 2021 and 30 October 2021 in the Pediatrics Clinic of Tekirdag Çorlu State Hospital. Serum vitamin D and zinc levels have been measured and NCSS (Number Cruncher Statistical System) program has been utilized for statistical analysis. RESULTS: We included 88 COVID-19 positive pediatric patients [50% (n = 44) female] and 88 healthy children [48.86% (n = 43) female] in this study. The mean serum vitamin D levels of COVID-19 positive patients were statistically significantly lower than the control group (p = 0.0001). The zinc mean values of the study group were found to be statistically significantly lower than the control group (p = 0.0001). There was a statistically significant correlation between serum vitamin D and zinc values in all patient groups (r = 0.245, p = 0.001). CONCLUSION: As a result, zinc and vitamin D levels were observed lower in COVID-19 patients than in healthy individuals. Since there is no defined treatment protocol for COVID-19 infection on children yet, zinc and vitamin D supplementation can be used as a supportive treatment in COVID-19 infection.

An Ethnobotanical Study of Medicinal Plants in Mersin (Turkey).

This comprehensive ethnobotanical study carried out in Mersin province, which is located in the southern part of Anatolia, east of the Mediterranean Sea, compiles details on plants used in folk medicine and ethnopharmacological information obtained through face-to-face interviews. The aim was to collect and identify plants used for therapeutic purposes by local people and to record information on traditional herbal medicine. Plant specimens were collected in numerous excursions. Additionally, informant consensus factor and use value (UV) were calculated for information gathered. This study identifies 93 plant taxa belonging to 43 families and records their usage in folk medicine; 83 taxa are wild and the remaining 10 are cultivated. The most commonly used plants belong to Lamiaceae, representing 15.0% of the total, while the Rosaceae, Malvaceae, Hypericaceae, Asteraceae and Cupressaceae families each represented another 5.4%. As a result of this investigation, we determine 189 medicinal usages of 93 taxa. The UV values indicate that the most important medicine plants are Hypericum perforatum (0.80), Cedrus libani (0.78), Quercus coccifera (0.77), Arum dioscoridis (0.76) and Juniperus drupaceae (0.74). We observed that most of the drugs are prepared using the infusion method (27.6%). As a conclusion, the study finds that traditional folk medicine usage is still common, especially among the rural population of Mersin.

Multicenter analysis of outcomes in blastic plasmacytoid dendritic cell neoplasm offers a pretargeted therapy benchmark.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an uncommon hematologic malignancy with poor outcomes. Existing data on the clinical behavior of BPDCN are limited because reported outcomes are from small retrospective series, and standardized treatment guidelines are lacking. The interleukin-3 cytotoxin conjugate tagraxofusp was recently tested in phase 1/2 trials that led to US Food and Drug Administration approval, the first ever for BPDCN. However, because there was no matched internal comparator in this or any clinical study to date, results of BPDCN trials testing new drugs are difficult to compare with alternative therapies. We therefore sought to define the clinical characteristics and outcomes of a group of patients with BPDCN treated at 3 US cancer centers in the modern era but before tagraxofusp was available. In 59 studied patients with BPDCN, the median overall survival from diagnosis was 24 months, and outcomes were similar in patients with "skin only" or with systemic disease at presentation. Intensive first-line therapy and "lymphoid-type" chemotherapy regimens were associated with better outcomes. Only 55% of patients received intensive chemotherapy, and 42% of patients underwent stem cell transplantation. Clinical characteristics at diagnosis associated with poorer outcomes included age >60 years, abnormal karyotype, and terminal deoxynucleotidyltransferase (TdT) negativity in the BPDCN cells. We also identified disease responses to pralatrexate and enasidenib in some patients. This study highlights poor outcomes for patients with BPDCN in the modern era and the need for new treatments. Outcomes from ongoing clinical trials for BPDCN can be evaluated relative to this contemporary cohort.

Influence of different extraction techniques on the chemical profile and biological properties of Anthemis cotula L.: Multifunctional aspects for potential pharmaceutical applications.

The phytochemical composition of different extracts obtained from stinking chamomile (Anthemis cotula L.) was investigated. Ethanol was used as solvent and accelerated solvent extraction (ASE), microwave assisted extraction (MAE), maceration, soxhlet extraction (SE), and ultrasound assisted extraction (UAE) were applied on plant material. Comparison of the phytochemical contents, antioxidant, and enzyme inhibitory properties were performed. The most abundant sesquiterpene in the extracts was anthecotuloide, while the most present phenolics were caffeoyl quinic acid, quercetin, and kaempferol derivatives. UAE extract was the most efficient in the extraction of sesquiterpenoids and polyphenols. Considering the assays on antioxidant activity and enzyme inhibition, ASE extract showed highest phenolic content (62.92 mg gallic acid equivalent/g extract). Likewise, this extract showed highest radical scavenging (103.44 mg trolox equivalent [TE]/g extract and 155.70 mg TE/g extract, for DPPH and ABTS assays respectively) and reducing power potential (435.32 and 317.89 mg TE/g extract, for CUPRAC and FRAP assays, respectively). The different extracts showed similar results in the enzyme inhibition assays suggesting that the extraction methods used have no effect on observed enzyme activities. Novelty of our findings are the inhibitory action of the ethanol extract of A. cotula aerial parts on key enzymes associated with Alzheimer's disease (acetyl cholinesterase, butyryl cholinesterase), type 2 diabetes (α-amylase, α-glucosidase), and skin hyperpigmentation disorders (tyrosinase). Data collected from the present work further appraises the multiple potential biological properties of stinking chamomile suggesting the need for further investigation on its constituents.

Anti-quorum sensing and anti-biofilm activities of Hypericum perforatum extracts against Pseudomonas aeruginosa.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypericum perforatum L. (Hypericaceae) has been used as a traditional therapeutic for skin wounds, burns, cuts and stomach ailments including stomach ache, ulcers for a long time in many societies. Although many studies about its antibacterial properties can be found, there is a lack of studies about its quorum sensing inhibition properties, which effects bacterial vulnerability directly, on Pseudomonas aeruginosa. AIM OF THE STUDY: Evaluation of anti-quorum sensing (anti-QS) and anti-biofilm activity of ethanol, methanol, acetone and ultra-sonicated extracts of Hypericum perforatum L. (HP) which is a well-known wound healer, against P. aeruginosa. MATERIALS AND METHODS: Aerial parts of HP were extracted with ethanol, methanol and acetone. In addition, separate extractions with ultrasonication were carried out with same solvents. Anti-QS activity tests with different doses of HP extracts were performed by employing biomonitor strains, of which the promoter of QS regulating and green fluorescent protein (GFP) genes were fusioned. For anti-biofilm activity, HP extracts were applied to wild type PAO1 strains and biofilm inhibition was quantified via crystal violet staining method. RESULTS: HP's ethanol, methanol and acetone extracts (250 µg/ml doses) inhibited LasIR signalling pathway up to 65.43%, 59.60%, 55.95% and same solvent extracts obtained with ultrasonication inhibited 71.33%, 64.47%, 57.35% respectively. Moreover, inhibition rates of RhlIR pathway were 28.80%, 50.83%, 45.84% for ethanol, methanol, acetone extracts (250 µg/ml doses) and 51.43%, 57.41%, 50.02% for ultrasonication extracts (250 µg/ml doses), compared to untreated controls. In the experiments, ethanol, methanol, acetone and ultra-sonicated extracts of HP did not inhibit biofilm formation. CONCLUSIONS: This study shows that HP plant is capable for blocking of las and rhl QS systems of P. aeruginosa. However, it was observed that ethanol, methanol and acetone extract of the plant samples did not show anti-biofilm activity against P. aeruginosa. This led us to thinking that biofilm formation was caused via another pathway such as IQS or PQS. Further studies with isolated active compounds of HP might give a better understanding of the effects on biofilm formation of P. aeruginosa.

Biologically active compounds from two members of the Asteraceae family: Tragopogon dubius Scop. and Tussilago farfara L.

Tragopogon dubius and Tussilago farfara are consumed as vegetables and used in folk medicine to manage common diseases. Herein, the chemical compositions and biological activities of different leaf extracts (ethyl acetate, methanol, and water) of T. dubius and T. farfara were evaluated. The antibacterial, antifungal, and antioxidant abilities of the extracts were tested using different assays including free radical scavenging, reducing power, phosphomolybdenum, and metal chelating assays. Enzyme inhibitory potentials were evaluated against cholinesterases, tyrosinase, α-amylase and α-glucosidase. Complexes of bioactive compounds (chlorogenic and rosmarinic acid) were docked into the enzymatic cavity of α-glucosidase and subjected to molecular dynamic calculation, enzyme conformational stability, and flexibility analysis. T. dubius and T. farfara extracts showed remarkable antioxidant potentials. Ethyl acetate extracts of T. dubius and T. farfara were the most potent inhibitors of acetylcholinesterase and butyrylcholinesterase. T. dubius ethyl acetate extract and T. farfara methanolic extract showed noteworthy activity against α-glucosidase. High performance liquid chromatography analysis revealed the abundance of some phenolic compounds including chlorogenic and rosmarinic acids. Ethyl acetate extract of T. dubius showed notable antifungal activity against all strains. Docking studies showed best pose for chlorogenic acid was stabilized by a network of hydrogen bonds with residues Asp1157, Asp1279, whereas rosmarinic acid showed several hydrogen bonds with Asp1157, Asp1420, Asp1526, Lys1460 and Trp1369. This study further validates the use of T. dubius and T. farfara in traditional medicine, as well as act as a stimulus for further studies for future biomedicine development. Communicated by Ramaswamy H. Sarma.

Paeonia arietina and Paeonia kesrounansis bioactive constituents: NMR, LC-DAD-MS fingerprinting and in vitro assays.

Paeonia species have been valued for their ethnomedicinal uses in various countries and received much interest among the scientific community for their therapeutic properties, including anti-microbial, anti-inflammatory, anti-cancer, nephroprotective and hepatoprotective effects. The multiple phytotherapeutical applications of Paeonia species inspired us to establish the phytochemical fingerprint and to evaluate the biological properties of ethyl acetate, methanol, and aqueous extracts from the roots and aerial parts of two Paeonia species (P. arietina G. Anderson and P. kesrounansis Thiébaut). Phytoconstituents of P. arietina and P. kesrounansis extracts were analyzed using 1D and 2D NMR and LC-DAD-ESI-MS. The total content of phenolics (TPC) and flavonoids (TFC) in the extracts was also evaluated. The antioxidant activity was profiled using DPPH, ABTS, CUPRAC, FRAP, phosphomolybdenum, and metal chelation assays. Enzyme inhibitory properties were evaluated against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, α-amylase, and α-glucosidase. Phytochemical analysis of P. arietina and P. kesrounansis extracts showed the presence of galloyl esters of sugars, galloyl monoterpenes, and glycosylated flavonoids. The three solvent extracts presented different behavior in the bioassays. The highest antioxidant activity, tyrosinase and AChE inhibition were observed for the methanolic extract of the aerial parts of P. kesrounansis. In addition, the ethyl acetate extracts of the aerial parts of both plants were the most effective inhibitors of α-amylase. The highest BChE inhibition was observed for root methanolic extract of P. kesrounansis while the root ethyl acetate extract of P. arietina exerted the strongest inhibition of α-glucosidase. Methanol extract of P. kesrounansis aerial parts presented the highest TPC, while TFC was greatest in the corresponding extract of P. arietina. Our findings can be considered as a starting point for future studies to further validate the effectiveness and safety profiles of these plants in folk medicine.

Targetable vulnerabilities in T- and NK-cell lymphomas identified through preclinical models.

T- and NK-cell lymphomas (TCL) are a heterogenous group of lymphoid malignancies with poor prognosis. In contrast to B-cell and myeloid malignancies, there are few preclinical models of TCLs, which has hampered the development of effective therapeutics. Here we establish and characterize preclinical models of TCL. We identify multiple vulnerabilities that are targetable with currently available agents (e.g., inhibitors of JAK2 or IKZF1) and demonstrate proof-of-principle for biomarker-driven therapies using patient-derived xenografts (PDXs). We show that MDM2 and MDMX are targetable vulnerabilities within TP53-wild-type TCLs. ALRN-6924, a stapled peptide that blocks interactions between p53 and both MDM2 and MDMX has potent in vitro activity and superior in vivo activity across 8 different PDX models compared to the standard-of-care agent romidepsin. ALRN-6924 induced a complete remission in a patient with TP53-wild-type angioimmunoblastic T-cell lymphoma, demonstrating the potential for rapid translation of discoveries from subtype-specific preclinical models.

New insights into the in vitro biological effects, in silico docking and chemical profile of clary sage - Salvia sclarea L.

Salvia sclarea L. is traditionally used to manage common human ailments and is consumed as a food product. This study aimed to establish the phytochemical profile and antioxidant potential of ethyl acetate, methanol, and water extracts of Salvia sclarea. The inhibitory action of the extracts against α-amylase, α-glucosidase, acetylcholinesterase, butyrylcholinesterase, and tyrosinase was also investigated. Methanol extract showed the highest phenolic and flavonoid contents (81.78 mg GAE/g extract and 40.59 mg RE/g extract, respectively). Reversed phase high performance liquid chromatography with diode array detector analysis revealed that S. sclarea was rich in rosmarinic acid. The water extract exhibited the lowest inhibitory activity against α-amylase but the upmost activity against α-glucosidase (0.19 and 18.24 mmol ACAE/g extract, respectively). Experimental data showed that only the water extract (8.86 mg KAE/g extract) significantly inhibited tyrosinase. Docking studies showed that quercetin binds to tyrosinase by two hydrogen and a pi-pi bonds. Salvia sclarea showed interesting biological activity against key enzymes involved in the pathogenesis of common ailments.

Phenolic components and assessment of biological properties of Tchihatchewia isatidea Boiss. extracts: Docking and functional approaches for designing novel products.

The potentiality of bioactive phenolic compounds may result in plant extracts having multiple biological activities. The aim of this study was to investigate into the biological activities of the methanolic, ethyl acetate, and water extracts of Tchihatchewia isatidea Boiss, an endemic medicinal plant of Turkey. The phenolic compositions of the extracts were confirmed using RP-HPLC. Extracts were screened for their potential antioxidant through a panoply of assays; their anti-diabetic potential, and plausible inhibitory activity against tyrosinase and acetylcholinesterase. Molecular modelling methods were also used to assess the docking properties of phenolic compounds on tyrosinase. The major and most abundant compounds were rosmarinic acid (570 ± 14 µg/g extract in the methanolic extract), ferrulic acid (336 ± 6 µg/g extract in the methanolic extract), (+)-catechin (340 ± 4 µg/g extract in the water extract), apigenin (182 ± 4 µg/g extract in the methanolic extract), and epicatechin (188 ± 12 µg/g extract in the water extract). Radical scavenging, reducing capacity, and metal chelating activities were detected in the extracts, with preponderance activity observed in the methanolic extract. In conclusion, the potential clinical applications observed during this study may provide new insights into the molecular aspect particularly for neuroprotective and anti-diabetic mechanisms involving oxidative stress.

Bioactivities of Achillea phrygia and Bupleurum croceum based on the composition of phenolic compounds: In vitro and in silico approaches.

This study presents the effects of the Achillea phrygia Boiss. et Bal. and Bupleurum croceum Fenzl. extracts obtained by different solvents (ethyl acetate, methanol and water) on selected enzyme inhibitory effects and antioxidant ability with screening bioactive compounds. Total and individual bioactive compounds were detected by spectrophotometric and HPLC-DAD techniques. Antioxidant abilities were evaluated by different methods including free radical scavenging (ABTS and DPPH), reducing power (CUPRAC and FRAP), phosphomolybdenum and metal chelating. Enzyme inhibitory effects were tested against cholinesterases, tyrosinase, amylase, glucosidase and lipase. Total phenolic contents were ranged from 20.52 mgGAE/g extract (B. croceum methanol extract) to 41.13 mgGAE/g extract (A. phrygia methanol extract). Generally, methanol and water extracts showed the strongest antioxidant abilities, while the ethyl acetate extracts had the most promising enzyme inhibitory effects. HPLC analysis revealed the abundance of some phenolics including rutin, quercetin, sinapic acid and chlorogenic acid, respectively. These components were also assessed using molecular modelling with the aim to study their docking properties on a set of six enzymes used in this study. Overall, these species could be suggested as valuable sources of natural-bioactive agents for developing new functional, pharmacological and health-promoting ingredients.

Gene expression profiling of pulmonary mucosa-associated lymphoid tissue lymphoma identifies new biologic insights with potential diagnostic and therapeutic applications.

We conducted comprehensive gene expression profiling (GEP) of primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma (n = 33) and compared the results to GEP of other B- and T-cell lymphomas and normal lymphocytes to identify novel markers and deregulated pathways. MALT has a prominent T-cell signature and a marginal zone/memory B-cell profile. Four novel transcripts were specifically overexpressed in MALT, and 2 of these, MMP7 and SIGLEC6, were validated at the protein level. GEP also revealed distinct molecular subsets in MALT. One subset, characterized by MALT1 translocations, showed overexpression of nuclear factor-kappaB (NF-KB) pathway genes but also was enriched for chemokine signaling pathways. Another subset showed increased plasma cells and a prominent plasma cell gene signature. By analyzing several genes with very high ("spiked") expression in individual cases, we identified clusters with different biologic characteristics, such as samples with MALT1 translocations having high expression of MALT1 and RARA, samples with plasmacytic differentiation having high FKBP11 expression, and samples with high RGS13 expression tending to have trisomy 3 and reactive follicles. In conclusion, MALT subgroups with distinct pathologic features defined by distinct groups of deregulated genes were identified. These genes could represent novel diagnostic and therapeutic targets.

Del(6)(q22) and BCL6 rearrangements in primary CNS lymphoma are indicators of an aggressive clinical course.

PURPOSE: Primary CNS lymphoma (PCNSL) is an aggressive lymphoma but clinically validated biologic markers that can predict natural history to tailor treatment according to risk are lacking. Several genetic changes including BCL6 rearrangements and deletion of 6q22, containing the putative tumor suppressor gene PTPRK, are potential risk predictors. Herein we determined the prevalence and survival impact of del(6)(q22) and BCL6, immunoglobulin heavy chain (IGH), and MYC gene rearrangements in a large PCNSL cohort treated in a single center. PATIENTS AND METHODS: Interphase fluorescence in situ hybridization was performed using two-color probes for BCL6, MYC, IGH-BCL6, and del(6)(q22) on thin sections of 75 paraffin-embedded samples from 75 HIV-negative, immunocompetent patients newly diagnosed with PCNSL. Survival data were analyzed using Kaplan-Meier survival curves, log-rank tests, and proportional hazards regression adjusting for age, deep structure involvement, and high-dose methotrexate (HDMTX) treatment. RESULTS: The prevalence of del(6)(q22) and BCL6, IGH, and MYC translocations was 45%,17%, 13%, and 3%, respectively. The presence of del(6)(q22) and/or a BCL6 translocation was associated with inferior overall survival (OS; P = .0097). The presence of either del(6)(q22) alone or a BCL6 translocation alone was also associated with inferior OS (P = .0087). Univariable results held after adjusting for age, deep structure involvement, and HDMTX. CONCLUSION: Del (6)(q22) and BCL6 rearrangements are common in PCNSL and predict for decreased OS independent of deep structure involvement and HDMTX. Unlike systemic diffuse large B-cell lymphoma, del(6)(q22) is common and IGH translocations are infrequent and usually involve BCL6 rather than BCL2, suggesting a distinct pathogenesis.