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We recently reported the cellular signal-modulating properties of altersolanol B (AB), a minor fungal tetrahydroanthraquinone (THAQ) metabolite, in the estrogen receptor positive (ER+) human breast adenocarcinoma cell lines, MCF-7 and T47D. MCF-7 (IC50 5.5 µM) and T47D (IC50 8.8 µM) were observed to be 4- and 2.4-fold more sensitive to the antiproliferative effects of AB, respectively, compared to MDA-MB-231 (triple-negative, IC50 21.3 µM). AB disrupted both AKT and ERK1/2 signaling leading to intrinsic apoptosis in MCF-7. The clinical limitations of multi-agent combination therapy that targets multiple pathways in cancer may potentially be circumvented by using a single molecule, such as AB, that inhibits both AKT and ERK1/2 signaling. The THAQ pharmacophore, with its disrupted conjugated ring system and relative redox inactivity, may possess greater mechanistic advantage against ER+ breast cancer when compared to the fully conjugated ring systems of the anthracyclines (doxorubicin) and anthraquinone (mitoxantrone) that are associated with nonselective mechanisms. The present phase of our study provides evidence that AB downregulated ERα expression at the post-translational level through the induction of proteasome-dependent degradation similar to a classical selective estrogen receptor degrader (SERD). AB dose-dependently downregulated both wild-type (WT)- and 17β-estradiol (E2)-stimulated ERα protein expression without altering mRNA expression in ER+ cells. This was corroborated by the marked reduction in the expression of downstream ERα target genes (cathepsin D and pS2). AB also dose-dependently downregulated cyclin D1, the estrogen-independent activator of ER. Antiproliferative effects were enhanced when ER+ cells were exposed to a combination of AB and the ERα-selective antagonist, MPP dihydrochloride. The AKT activator, SC79, showed that the AB-induced ERα protein downregulation was independent of the inhibition of AKT-FOXO1 signaling. The expression of Hsp90 was not affected. Co-treatment with the protein synthesis inhibitor, cycloheximide, revealed that AB downregulated ERα expression at the post-translational level. The proteosome inhibitor, MG-132, effectively suppressed AB-induced ERα degradation and restored cellular proliferation. In silico approaches were adopted to probe the direct binding of AB to ERα. AB demonstrated significant binding affinity with human ERα (PDB ID - 3ert) compared to the binding of the standard SERD, fulvestrant. Non-covalent bonding interaction analysis further revealed that, much like fulvestrant, AB successfully interacted with 5 major amino acid residues (i.e., Ala350, Asp351, Leu525, Leu536 and Trp383) at the ligand-binding domain of ERα which is stabilized by 7 non-bonding interactions. Principal component analysis indicated that binding with AB improved the compactness of 3ert folding. Molecular dynamics simulation indicated that the 3ert-AB interaction was stable even in the 100 ns simulated physiological environment. Citation Format: Md Afjalus Siraj, Md Sajjadur Rahman, Aaron T. Jacobs, Ghee T. Tan. Altersolanol B, a fungal metabolite, induces proteasome-dependent degradation of estrogen receptor α (ERα) and inhibits downstream signaling targets in ER+ breast adenocarcinoma cells [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-24-08.

Financiaciado para publicación en acceso aberto: Universidade de Vigo/CISUG Gout is an inflammatory disease caused by metabolic disorder or genetic inheritance. People throughout the world are strongly dependent on eth- nomedicine for the treatment of gout and some receive satisfactory curative treatment. The natural remedies as well as established drugs derived from natural sources or synthetically made exert their action by mechanisms that are closely associated with anticancer treatment mechanisms regarding inhibition of xanthine oxidase, feedback inhibition of de novo purine synthesis, depolymerization and disappearance of microtubule, inhibition of NF- ĸ B activation, induction of TRAIL, promotion of apoptosis, and caspase activation and proteasome inhibition. Some anti-gout and anticancer novel compounds interact with same receptors for their action, e.g ., colchicine and colchicine analogues. Dietary flavonoids, i.e ., chrysin, kaempferol, quercetin, fisetin, pelargonidin, apigenin, luteolin, myricetin, isorhamnetin, phloretinetc etc. have comparable IC 50 values with established anti-gout drug and effective against both cancer and gout. Moreover, a noticeable number of newer anticancer compounds have already been isolated from plants that have been using by local traditional healers and herbal practitioners to treat gout. Therefore, the anti-gout plants might have greater potentiality to become selective candidates for screening of newer anticancer leads.

Many cancers carry change-of-function mutations affecting RNA splicing factors, however, less is known about the functional consequences of upregulated RNA splicing factors in cancer. Here, we demonstrate that SMNDC1, a poorly studied splicing factor, which we found to be upregulated in multiple carcinomas and associated with poor patient prognosis, promotes cell proliferation, clonal expansion, and tumor growth by promoting the retention of G-rich exons, which otherwise would be excluded or retained at a lower rate after RNA splicing in normal cells. Inclusion of exon 4 (E4) of MAPK3 (ERK1), which encodes both kinase phosphorylation sites (Thr202/Tyr204), was among the promoted exons by SMNDC1. Forced exclusion of MAPK3-E4 using anti-sense oligos inhibited the ERK1 phosphorylation, expression of target genes and decreased tumor cell growth. These data support that cancer cells exploit a “splicing switch” to promote ERK kinase activity and offer a druggable alternative to block oncogenic signaling and altered RNA splicing in cancer cellsSIGNIFICANCEERK signaling promotes tumor growth and survival. Exon 4 of MAPK3 (ERK1) encodes the activation phosphorylation sites of ERK1 kinase. Aberrant RNA splicing induced by SMNDC1 in cancer cells increases the retention of exon 4 during mRNA splicing, unleashes the kinase activity. SMNDC1 potentializes as a cancer therapeutic target.

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer death. We previously reported keratin 17 (K17) as a novel negative prognostic and predictive biomarker, whose overexpression confers the resistance to chemotherapies. Here, we investigated the mechanisms of chemoresistance and tumor-specific vulnerabilities that can be exploited for targeted therapies for K17-expressing PDAC. Unbiased metabolomic studies in isogenic PDAC models identified several key metabolic pathways that are upregulated in the presence of K17. We demonstrate that K17 increases pyrimidine biosynthesis, a pathway that has been linked to chemoresistance. Patient dataset analysis revealed that K17 expression and enzymes involved in pyrimidine, but not purine, de novo biosynthesis is associated with shorter patient survival. Rescue experiments showed that deoxycytidine (dC) and deoxythymidine (dT) were sufficient to promote resistance to Gemcitabine (a dC analog) and 5-fluorouracil (a dT analog), respectively. Furthermore, K17-expressing cells were more sensitive to Brequinar, a specific inhibitor of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme in de novo pyrimidine biosynthetic pathway. Targeting DHODH by small interfering RNA or by Brequinar with Gemcitabine synergistically inhibited the viability of K17-positive PDAC cells. Importantly, the combination of Gemcitabine and Brequinar significantly inhibited the growth of K17-expressing tumors and extended survival of mice bearing K17-expressing PDACs. Overall, we identified a novel pathway of chemoresistance and a metabolic target of which could lead to the development of a biomarker-based therapy for K17-expressing PDAC.

Prostate cancer-associated transcript 1 (PCAT1) is a long non-coding RNA (lncRNA), composed of more than 200 nucleotides. Its expression controls the proliferation, migration, invasion, and metastasis of different cancer. In the current study, we conducted a patient data derived metanalysis to study the possible role of PCAT1 as a prognostic biomarker for the invasive breast cancer (IBC). Our analysis demonstrated that, PCAT1 highly expressed in BRCA mutated BC patients’ cells compared to normal cells (fold change ~ 1.56). The overall survival rate of patients with higher PCAT1 expression significantly (p- 5.539e− 5) reduced over time. Moreover, PCAT1 was significantly altered in PR (p- 1.672e-6), HER2 (p- 3.190e-6) negative and ER (p- 3.920e-4) positive primary IBC samples. In addition, alteration of PCAT1 also correlated with the histologic grade of the IBC (p- >10− 10). On top of that, we found co-occurrence of PCAT1 with the oncogenes of CASC family i.e., CASC8, CASC11, and CASC19 in IBC. The genomic location of PCAT1, CASC8, CASC11, and CASC19 was chr8q24 and chr8q24 respectively which contains the loci responsible for different cancers including BC. In addition, the CASC8 and CASC19 overlapped with PCAT1 in genomic sequence. Taken together, PCAT1 expression is associated with poor clinical outcomes and co-occur with previously established oncogenes and biomarkers which suggest its usefulness as a prognostic biomarker for IBC.

When tested in the acetic acid-induced writhing and formalin-induced paw-licking tests, the ethanol extract of Vernonia patula (VP) aerial parts showed significant antinociceptive activity. In neuropharmacological tests, it also significantly delayed the onset of sleep, increased the duration of sleeping time, and significantly reduced the locomotor activity and exploratory behaviour of mice. Five phenolic compounds, namely gallic acid, vanillic acid, caffeic acid, quercetin and kaempferol, were detected in VP following HPLC-DAD analysis. The presence of these phenolic compounds in VP provides some support for the observed antinociceptive and sedative effects. A computational study was performed to predict the binding affinity of gallic acid, vanillic acid, caffeic acid, quercetin and kaempferol towards the cannabinoid type 1 (CB1) receptor. Caffeic and vanillic acid showed the highest probable ligand efficiency indices towards the CB1 target. Vanillic acid displayed the best blood brain barrier penetration prediction score. These findings provide some evidence for the traditional use of VP to treat pain.

ROS, RNS, and carcinogenic metabolites generate excessive oxidative stress, which changes the basal cellular status and leads to epigenetic modification, genomic instability, and initiation of cancer. Epigenetic modification may inhibit tumor-suppressor genes and activate oncogenes, enabling cells to have cancer promoting properties. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that in humans is encoded by the NFE2L2 gene, and is activated in response to cellular stress. It can regulate redox homoeostasis by expressing several cytoprotective enzymes, including NADPH quinine oxidoreductase, heme oxygenase-1, UDP-glucuronosyltransferase, glutathione peroxidase, glutathione-S-transferase, etc. There is accumulating evidence supporting the idea that dietary nutraceuticals derived from commonly used fruits, vegetables, and spices have the ability to produce cancer chemopreventive activity by inducing Nrf2-mediated detoxifying enzymes. In this review, we discuss the importance of these nutraceuticals in cancer chemoprevention and summarize the role of dietary terpenoids in this respect. This approach was taken to accumulate the mechanistic function of these terpenoids to develop a comprehensive understanding of their direct and indirect roles in modulating the Keap1-Nrf2-ARE signaling system.

Many cancers carry recurrent, change-of-function mutations affecting RNA splicing factors, however, less is known about the consequences of upregulated RNA splicing factors (SFs) in cancer. Here, we describe a role of survival motor neuron domain containing 1 (SMNDC1) protein, a poorly studied SF that we found to be upregulated in pancreatic ductal adenocarcinoma (PDAC) and high-grade serous ovarian cancers (HGSOCs) and associated with poor patient prognosis. By loss- and gain-of- function approaches we found that SMNDC1 promotes cancer cell proliferation, clonal expansion and tumor growth. Mechanistically, SMNDC1 promoted the retention of A/C-rich exons which otherwise would be excluded or less retained after RNA splicing in normal cells. Inclusion of exon 4 (E4) of MAPK3 (ERK1), which encodes both phosphorylation sites (Thr202/Tyr204) of the kinase, was among the promoted exons by SMNDC1. Forced exclusion of MAPK3 E4 using anti-sense oligos in vitro and in vivo, inhibited the phosphorylation of ERK1/2, the expression of downstream genes (Cyclin D1, Elk1) and increased proapoptotic proteins. These data provide a novel mechanism by which PDAC and HGSOC cells exploit a “splicing switch” that increases ERK1 phosphorylation, and offer a druggable alternative to target these cancer cells by jointly blocking oncogenic signaling and altered RNA splicing. Citation Format: Yushan Zhang, Md Afjalus Siraj, Prabir Chakrabarty, Robert Tseng, Shamik Das, Resham Bhattacharya, Luisa Escobar-Hoyos, Priyabrata Mukherjee. Activation of the MAPK pathway by altered RNA splicing in cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B062.

Pancreatic ductal adenocarcinomas (PDACs) are highly lethal, mostly because they quickly develop resistance to current chemotherapies: Gemcitabine (GEM)/paclitaxel or cocktail FOLFIRINOX. Both chemotherapies rely on nucleoside analogues (GEM and 5-fluorouracil [5-FU], and resistance is developed without acquiring mutations, suggesting the role of non-mutational mechanisms for therapy resistance. Our recent findings demonstrated that PDACs depend on RNA splicing proteins to maintain tumors and are exquisitely susceptible to a range of therapies directed at RNA splicing, supporting the role of aberrant RNA splicing in PDAC therapy resistance. Here we evaluated the role of altered RNA splicing in PDAC therapy resistance. Three murine and human isogenic lines with either sensitivity or resistance to GEM were developed. We performed deep RNA sequencing (RNASeq, 80-100 million reads, traditional is 20-40 million reads), differential gene expression, and splicing analyses. GEM resistant PDAC cells demonstrated >40% of non-canonical RNA splice variants and altered expression of 30% of RNA-binding proteins encoded in the human/murine genome, compared to GEM sensitive ones. Specific alternatively spliced exons with common cis-elements were identified in therapy resistant cells, suggesting that these splicing changes are guided by a splicing factor or other RNA-binding protein(s) (RBPs). Top splicing changes were associated to mRNAs encoding ether lipid and pyruvate metabolism. This finding is important as previous studies have linked these metabolic pathways to therapy resistance, however, they have overlooked if protein isoforms, resulting from aberrant splicing, have different impacts in therapy resistance. In addition, GEM and H3B-8800, a novel spliceosome inhibitor showed higher synergistic activity in GEM resistant PDAC cells compared to GEM sensitive cells, suggesting that the development of resistance in PDAC is highly dependent on RNA splicing. Combinedly, these data strongly suggest that resistance to chemotherapeutic agents in PDAC cells requires altered RNA splicing and aberrant expression of associated proteins. Further investigation is ongoing to identify the splicing events and RBPs related to chemotherapy resistance, which will uncover novel mechanisms of therapy resistance and therapeutic modalities by targeting RNA splicing in pancreatic cancer. Citation Format: Md Afjalus Siraj, Xinning Shan, Robert Tseng, Luisa Escobar-Hoyos. Evaluating the role of altered RNA metabolism in pancreatic cancer therapy resistance [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B045.

Objective: Oxidative stress leads to numerous physiological disorders including infectious diseases, inflammation, and cancer. The present study was carried out to investigate antioxidant, antibacterial, and cytotoxic activity of methanol crude extract of leaves and fruits of the Ficus racemosa (LCME and FCME, resp.) and to analyse its major bioactive polyphenols by HPLC-DAD. F. racemosa has various uses in traditional medicine in the subcontinent for treating an array of diseases. Methods: Antioxidant capacity of the extracts was evaluated by DPPH free radical scavenging, reducing power, total phenolic, total flavonoid, total tannin content assay, superoxide radical, hydroxyl radical, and hydrogen peroxide scavenging assay. Identification and quantification of bioactive polyphenols were done by HPLC-DAD method. Antibacterial activity was tested by “disc diffusion” method. Brine shrimp lethality assay was carried out to check the cytotoxic potential. Results: Both LCME and FCME showed DPPH scavenging ability and concentration dependent reducing power activity. They had phenolic content, flavonoid content, and tannin content. Both the extracts showed superoxide radical scavenging ability, hydroxyl radical scavenging ability, and hydrogen peroxide scavenging ability. HPLC analysis of LCME and FCME indicated the presence of significant amount of gallic acid along with other phenolic constituents. Conclusion: Significant amount of gallic acid along with other phenolic constituents might have played an important role in the observed antioxidant, antibacterial, and cytotoxic activity.

A molecular docking approach was employed to evaluate the binding affinity of six triterpenes, namely epifriedelanol, friedelin, α-amyrin, α-amyrin acetate, β-amyrin acetate, and bauerenyl acetate, towards the cannabinoid type 1 receptor (CB1). Molecular docking studies showed that friedelin, α-amyrin, and epifriedelanol had the strongest binding affinity towards CB1. Molecular dynamics simulation studies revealed that friedelin and α-amyrin engaged in stable non-bonding interactions by binding to a pocket close to the active site on the surface of the CB1 target protein. The studied triterpenes showed a good capacity to penetrate the blood–brain barrier. These results help to provide some evidence to justify, at least in part, the previously reported antinociceptive and sedative properties of Vernonia patula.

A molecular docking approach was employed to evaluate the binding affinity of six triterpenes, namely epifriedelanol, friedelin, α-amyrin, α-amyrin acetate, β-amyrin acetate, and bauerenyl acetate, towards the cannabinoid type 1 receptor (CB1). Molecular docking studies showed that friedelin, α-amyrin, and epifriedelanol had the strongest binding affinity towards CB1. Molecular dynamics simulation studies revealed that friedelin and α-amyrin engaged in stable non-bonding interactions by binding to a pocket close to the active site on the surface of the CB1 target protein. The studied triterpenes showed a good capacity to penetrate the blood–brain barrier. These results help to provide some evidence to justify, at least in part, the previously reported antinociceptive and sedative properties of Vernonia patula.

The present study focused on the apoptosis-inducing effects and cellular signal-modulating properties of altersolanol B (AB), a minor fungal tetrahydroanthraquinone (THAQ) metabolite, in the estrogen receptor positive (ER+) human breast adenocarcinoma cell line, MCF-7. AB demonstrated approximately 4-fold greater antiproliferative activity in ER+ MCF-7 cells (IC

The Sundarbans forest in Bangladesh is the world's largest mangrove. It is a unique ecosystem where living organisms face extreme challenges to compete for survival. Such competition results in the production of bioactive molecules which are useful for agriculture and human health. In this study, eighty fungal endophytes from nine mangrove plants growing in a region, as yet unexplored, of the Sundarbans were isolated by surface sterilisation and pure culture techniques. Among the eighty isolates subjected to a preliminary antimicrobial screening using an agar plug diffusion assay, only fifteen showed some promising activity. These were subsequently identified by polymerase chain reaction of their ITS gene. Extracts prepared from the identified isolates were screened for antimicrobial, antioxidant, cytotoxic and α-glucosidase inhibitory activities. Their total polyphenol and flavonoid content and their FRAP value were also determined. All endophytes are reported for the first time in the plants under investigation.

Ethnopharmacological relevance The present study was designed to investigate the regulation of the redox signaling and inflammation by ethanolic leaf extract of Terminalia myriocarpa Van Heurck & Muller (ETM), inspired by the reported antioxidant potential of the plant bark and the anti-edema effect of the same genus. Materials and methods HPLC-DAD dereplication study was conducted to detect the major polyphenolic secondary metabolites. In-vitro DPPH free radical scavenging assay, nitric oxide (NO) scavenging assay, Fe2+ ion chelating ability assay and reducing power assay were conducted to evaluate the antioxidant capacity. The molecular mechanism of anti-inflammation was investigated via assessing the NO and NF-ĸB inhibiting properties in different cell lines. In-vivo carrageenan and histamine-induced edema tests were conducted using established animal models. Pro-inflammatory proteins iNOS and NF-κB were docked against the major metabolites of ETM in the in-silico study. Results HPLC dereplication analysis revealed the presence of considerable amount of ellagic acid, where methyl-(S)-flavogallonate was previously reported in T. myriocarpa. Significant antioxidant activity was found in every in- vitro redox assay conducted. NO was reduced in RAW 264.7 cells, showing 83.67 ± 4.18% inhibitory activity at the highest tested concentration. TNF-α induced NF-κB was also observed to be reduced in 293/NF-кB-luc cells with an inhibitory activity of 66.23 ± 0.81% at the highest dose tested. In-vivo carrageenan-induced edema test demonstrated significant anti-inflammatory activity (p Conclusion Mentionable basis was found on behalf of the anti-inflammatory and antioxidant potentials of ETM which might be correlated with its NF-ĸB inhibiting properties.

Purpose: Inflammation and oxidative stress can lead to different chronic diseases including cancer and atherosclerosis. Many medicinal plants have the potential to show as anti-inflammatory activity. Present investigation was performed to investigate anti-inflammatory, antioxidant activity, and quantification of selected bioactive plant polyphenols of the ethanol (EAH) and aqueous (AAH) extracts of Acalypha hispida (Euphorbiaceae) leaves. Methods: Anti-inflammatory activity was evaluated by carragenan and histamine induced rat paw edema models while antioxidant capacity was evaluated by DPPH free radical scavenging, Fe+2 chelating ability, reducing power, NO scavenging, total phenolic and total flavonoid content assay. Identification and quantification of bioactive polyphenols was done by HPLC. Results: At the doses of 200 and 400 mg/kg, both EAH and AAH showed statistically significant inhibition of paw volume in the anti-inflammatory activity test. Both the extracts showed DPPH scavenging (IC50: 14 and 17 µg/ml, respectively), Fe+2 ion chelating (IC50: 40 and 46 µg/ml, respectively), NO scavenging activity (65.49 and 60.66% inhibition at 100 µg/ml), and concentration dependent reducing power ability. For EAH and AAH, flavonoid content was 126.30 and 149.72 mg QE/g dry extract, while phenolic content was 130.51 and 173.80 mg GAE/g dry extract, respectively. HPLC analysis of EAH and AAH indicated the presence of high content of ellagic acid along with other phenolic constituents. Conclusion: High content of ellagic acid along with other phenolic constituents might have played an important role in the observed anti-inflammatory and antioxidant activity.

The objective of the present study was to investigate the phytochemical nature (group determination of plant constituents) as well as the antioxidant and analgesic activity of ethanolic extract of the Cerbera manghas L. leaves (Family: Apocynaceae) . Phy tochemical an alysis of ethanolic extract of Cerbera manghas leaves indicated the presence of carbohydrate (reducing sugars), alkaloids, tannins, steroids, flavonoids & glycosides. The extract exhibited significant (P

Background. Ficus hispida is traditionally used in the ailment of pain, inflammation, and neurological disorders. The present study set out to evaluate the in vivo antinociceptive, anti-inflammatory, and sedative activity of the ethanol extract of Ficus hispida bark (EFHB). Methods. The antinociceptive activity of EFHB was evaluated by using acetic acid induced writhing, formalin, hot plate, and tail immersion methods in Swiss albino mice. Its anti-inflammatory activity was assessed by using carrageenan and histamine induced rat paw oedema test in Wister rats. The central stimulating activity was studied by using pentobarbital induced hypnosis, hole cross, and open field tests in Swiss albino mice. Results. EFHB demonstrated antinociceptive activity both centrally and peripherally. It showed 62.24% of writhing inhibition. It significantly inhibited licking responses in early (59.29%) and late phase (71.61%). It increased the reaction time to the thermal stimulus in both hot plate and tail immersion. It inhibited the inflammation to the extent of 59.49%. A substantial increase in duration of sleep up to 60.80 min and decrease of locomotion up to 21.70 at 400 mg/kg were also observed. Conclusion. We found significant dose dependent antinociceptive, anti-inflammatory, and sedative properties of EFHB in experimental animal models.

Objective. Oxidative stress leads to numerous physiological disorders including infectious diseases, inflammation, and cancer. The present study was carried out to investigate antioxidant, antibacterial, and cytotoxic activity of methanol crude extract of leaves and fruits of the Ficus racemosa (LCME and FCME, resp.) and to analyse its major bioactive polyphenols by HPLC-DAD. Methods. Antioxidant capacity of the extracts was evaluated by DPPH free radical scavenging, reducing power, total phenolic, total flavonoid, total tannin content assay, superoxide radical, hydroxyl radical, and hydrogen peroxide scavenging assay. Identification and quantification of bioactive polyphenols were done by HPLC-DAD method. Antibacterial activity was tested by “disc diffusion” method. Brine shrimp lethality assay was carried out to check the cytotoxic potential. Result. Both LCME and FCME showed DPPH scavenging ability and concentration dependent reducing power activity. They had phenolic content, flavonoid content, and tannin content. Both the extracts showed superoxide radical scavenging ability, hydroxyl radical scavenging ability, and hydrogen peroxide scavenging ability. HPLC analysis of LCME and FCME indicated the presence of significant amount of gallic acid along with other phenolic constituents. Conclusion. Significant amount of gallic acid along with other phenolic constituents might have played an important role in the observed antioxidant, antibacterial, and cytotoxic activity.

Central pontine myelinolysis (CPM) is a complication of treatment of patients with severe hyponatremia. The microscopic appearance of central pontine myelinolysis is loss of myelin with sparing of axons, without evidence of inflammation. The abnormalities associated with central pontine myelinolysis are readily identified on magnetic resonance imaging scans. A patient with central pontine myelinolysis following rapid correction of hyponatremia was studied with magnetic resonance imaging soon after onset of tetraplegia & dysarthria. Affected central pontine white matter showed restricted diffusion on diffusion-weighted images associated with hyper signal on T2-W & FLAIR images. MRI with dedicated sequences is the modality of choice for early detection of osmotic changes in the brain.DOI: http://dx.doi.org/10.3329/cmoshmcj.v13i1.19427

Background Garo Hills represents one of earliest human habitation in Bangladesh preserving its ancient cultures due to the geographic location. It is situated in the most northern part of Durgapur sub-district having border with Meghalaya of India. Durgapur is rich in ethnic diversity with Garo and Hajong as the major ethnic groups along with Bangalee settlers from the mainstream population. Thus the ethnomedicinal practice in Garo Hills is considered rich as it encompasses three different groups. Present survey was undertaken to compile the medicinal plant usage among the various communities of the Garo Hills. Methods The ethnomedicinal data was collected through open and focussed group discussions, and personal interviews using semi-structured questionnaire. A total of 185 people were interviewed, including the three community people and their traditional health practitioners (THPs). The usage of the plants were further analysed and are presented as use value (UV), informant consensus factor (ICF) and fidelity level (FL). Results A total of 71 plants from 46 families and 64 genera were documented during our survey. Gastrointestinal disorders represented the major ailment category with the use of 36 plant species followed by dermatological problems (25 species). The ICF ranged from 0.90 to 0.99, with an average value of 0.96. Leaves (41) were the principle source of medication followed by fruits (27). Trees (33) were the major plant type used in the ethnobotanical practice. A total of 25 plants showed high FL (70.91 to 100 %) with 12 plants showing maximum FL (100 %). A number of the plants appear to have unique ethnomedicinal uses. Conclusion Present investigation revealed a rich traditional practice in the studied region, which provides primary health care to the local community. This compilation of the ethnobotanical knowledge can help researchers to identify the uses of various medicinal plants that have a long history of use.