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Antibacterial and cytotoxic activities of the Syzygium polyanthum leaf extract from Malaysia

Nordin ML, Othman AA, Kadir AA, Shaari R, Osman AY, Mohamed M

Vet World, 2019;12(2):236-242.
PMID: 31040564 DOI: 10.14202/vetworld.2019.236-242

Background and Aim: The increasing prevalence of drug resistance eventually leads scientist to discover new drugs that could solve the problem. Since ancient immemorial times, medicinal plants generally known as herbs were widely used in every culture throughout the world. In fact, currently up to 70,000 plant species have been screened for biological activities and about 70% ends up for commercialization. Therefore, this study was aimed to evaluate the potential cytotoxic and antibacterial effect of Syzygium polyanthum leaves which are local Malaysia plants, against 4T1 and MCF-7 mammary carcinoma cells, respectively, and also against bacteria causing mastitis in cows.
Materials and Methods: The cytotoxic effect of hydromethanolic extract of S. polyanthum against 4T1 and MCF-7 mammary carcinoma cells was evaluated using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The cells were treated with the concentration of extracts ranging from 15.63 µg/mL to 1000 µg/ml for 72 h, and the percentage of cell survivability was determined based on minimum concentration that was able to allow at least 50% growth of cancer cells (IC50) after 72 h. The antibacterial activity was tested against common bacteria causing mastitis in cow. The bacteria were isolated from milk samples. The antibacterial activity of the extract was determined by disk diffusion method and susceptibility test based on minimum inhibitory concentration (MIC).
Results: Staphylococcus aureus, Staphylococcus hyicus, and Staphylococcus intermedius were isolated from the milk samples that positive for mastitis. The MIC values range from 7.12 mm to 13.5 mm. The extract exhibits the widest zone of inhibition (13.5±0.20 mm) at 1000 mg/ml of concentrations. The extract relatively has low cytotoxicity effect against 4T1 and MCF-7 cells with IC50 values ranging from 672.57±59.42 and 126.05±50.89 µg/ml, respectively.
Conclusion: S. polyanthum exerts weak antibacterial activity and cytotoxic effect to mammary carcinoma cells. The extract does not toxic to cells. However, further study is recommended, especially, this plant should be tested for in vivo.

Matched MeSH terms: MCF-7 Cells
Preparation of letrozole dispersed pHEMA/AAm-g-LDPE drug release system: In-vitro release kinetics for the treatment of endometriosis

Siddiqa AJ, Shrivastava NK, Ali Mohsin ME, Abidi MH, Shaikh TA, El-Meligy MA

Colloids Surf B Biointerfaces, 2019 Jul 01;179:445-452.
PMID: 31005739 DOI: 10.1016/j.colsurfb.2019.04.014

This paper focuses on the development of a drug delivery system for systemically controlled release of a poorly soluble drug, letrozole. The work meticulously describes the preparation and characterizations of 2-hydroxyethyl methacrylate (HEMA) polymerization onto hydrophilic acrylamide grafted low-density polyethylene (AAm-g-LDPE) surface for targeted drug release system. The surface morphology and thickness measurement of coated pHEMA layer were measured using scanning electron microscopy (SEM). The swelling study was done in deionized (DI) water and simulated uterine fluid (SUF, pH = 7.6). In vitro release of letrozole from the system was performed in SUF. Further, the release kinetics of letrozole from the system was studied using different mathematical models. The results, suggest that the rate of drug release can be altered by varying the concentrations of cross-linker in pHEMA. The optimized sample released 72% drug at the end of 72 h of measurement.

Matched MeSH terms: NIH 3T3 Cells
Probing the characteristics and biofunctional effects of disease-affected cells and drug response via machine learning applications

Mudali D, Jeevanandam J, Danquah MK

Crit Rev Biotechnol, 2020 Nov;40(7):951-977.
PMID: 32633615 DOI: 10.1080/07388551.2020.1789062

Drug-induced transformations in disease characteristics at the cellular and molecular level offers the opportunity to predict and evaluate the efficacy of pharmaceutical ingredients whilst enabling the optimal design of new and improved drugs with enhanced pharmacokinetics and pharmacodynamics. Machine learning is a promising in-silico tool used to simulate cells with specific disease properties and to determine their response toward drug uptake. Differences in the properties of normal and infected cells, including biophysical, biochemical and physiological characteristics, plays a key role in developing fundamental cellular probing platforms for machine learning applications. Cellular features can be extracted periodically from both the drug treated, infected, and normal cells via image segmentations in order to probe dynamic differences in cell behavior. Cellular segmentation can be evaluated to reflect the levels of drug effect on a distinct cell or group of cells via probability scoring. This article provides an account for the use of machine learning methods to probe differences in the biophysical, biochemical and physiological characteristics of infected cells in response to pharmacokinetics uptake of drug ingredients for application in cancer, diabetes and neurodegenerative disease therapies.

Matched MeSH terms: Cells, Cultured
Fulltext A Synthetic Curcuminoid Analogue, 2,6-Bis-4-(Hydroxyl-3-Methoxybenzylidine)-Cyclohexanone (BHMC) Ameliorates Acute Airway Inflammation of Allergic Asthma in Ovalbumin-Sensitized Mice

Tham CL, Yeoh SY, Ong CH, Harith HH, Israf DA

Mediators Inflamm, 2021;2021:9725903.
PMID: 33883974 DOI: 10.1155/2021/9725903

2,6-Bis-(4-hydroxyl-3-methoxybenzylidine) cyclohexanone (BHMC), a synthetic curcuminoid analogue, has been shown to exhibit anti-inflammatory properties in cellular models of inflammation and improve the survival of mice from lethal sepsis. We further evaluated the therapeutic effect of BHMC on acute airway inflammation in a mouse model of allergic asthma. Mice were sensitized and challenged with ovalbumin (OVA), followed by intraperitoneal administration of 0.1, 1, and 10 mg/kg of BHMC. Bronchoalveolar lavage fluid, blood, and lung samples were collected, and the respiratory function was measured. OVA sensitization and challenge increased airway hyperresponsiveness (AHR) and pulmonary inflammation. All three doses of BHMC (0.1-10 mg/kg) significantly reduced the number of eosinophils, lymphocytes, macrophages, and neutrophils, as well as the levels of Th2 cytokines (IL-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF) as compared to OVA-challenged mice. However, serum level of IgE was not affected. All three doses of BHMC (0.1-10 mg/kg) were effective in suppressing the infiltration of inflammatory cells at the peribronchial and perivascular regions, with the greatest effect observed at 1 mg/kg which was comparable to dexamethasone. Goblet cell hyperplasia was inhibited by 1 and 10 mg/kg of BHMC, while the lowest dose (0.1 mg/kg) had no significant inhibitory effect. These findings demonstrate that BHMC, a synthetic nonsteroidal small molecule, ameliorates acute airway inflammation associated with allergic asthma, primarily by suppressing the release of inflammatory mediators and goblet cell hyperplasia to a lesser extent in acute airway inflammation of allergic asthma.

Matched MeSH terms: Goblet Cells
Cutaneous involvement of multiple myeloma

Mohtarrudin N, Bakrin IH, Ambrose D, Jo Lyn L, Mukhtar NSA

Malays J Pathol, 2021 Apr;43(1):75-79.
PMID: 33903309

Cutaneous multiple myeloma (MM) is a rare disease. It can be primary or secondary in origin. The secondary type is further classified into specific and nonspecific types. The specific type is uncommon and is known as a secondary cutaneous plasmacytoma. We report a case of secondary cutaneous plasmacytoma in a 58-year-old man who had a history of plasma cell tumour of the lung and multiple myeloma. He achieved complete remission after the completion of chemotherapy and autologous stem cell transplant (ASCT). However, five months later, he developed multiple erythematous nodules on the whole body. Skin biopsy revealed diffuse neoplastic cells infiltrate in the reticular dermis with sparing of the upper papillary dermis and epidermis. The neoplastic cells were monotonous and homogenous with variable degrees of cytological atypia. Occasional cells showed distinctive plasma cell features. Plasma cell lineage was confirmed with CD138. The cells were immunoreactive to Kappa. Ki-67 was greater than 90%. They were non-immunoreactive to CD45, CD3, CD20, CD79 alpha and CK AE1/AE3. The findings were consistent with secondary cutaneous plasmacytoma. Our case illustrates that MM may present with nonspecific dermatological manifestations. As specific cutaneous involvement of MM is very uncommon; a high degree of clinical suspicion, detailed medical history and histopathological examination are required to arrive at an early diagnosis.

Matched MeSH terms: Plasma Cells
Fulltext Pharmacological Evaluation of Safoof-e-Pathar Phori- A Polyherbal Unani Formulation for Urolithiasis

Ahmad W, Khan MA, Ashraf K, Ahmad A, Daud Ali M, Ansari MN, et al.

Front Pharmacol, 2021;12:597990.
PMID: 33935697 DOI: 10.3389/fphar.2021.597990

Safoof-e-Pathar phori (SPP) is an Unani poly-herbomineral formulation, which has for a long time been used as a medicine due to its antiurolithiatic activity, as per the Unani Pharmacopoeia. This powder formulation is prepared using six different plant/mineral constituents. In this study, we explored the antiurolithiatic and antioxidant potentials of SPP (at 700 and 1,000 mg/kg) in albino Wistar rats with urolithiasis induced by 0.75% ethylene glycol (EG) and 1% ammonium chloride (AC). Long-term oral toxicity studies were performed according to the Organization for Economic Co-operation and Development (OECD) guidelines for 90 days at an oral dose of 700 mg/kg of SPP. The EG urolithiatic toxicant group had significantly higher levels of urinary calcium, serum creatinine, blood urea, and tissue lipid peroxidation and significantly (p < 0.001 vs control) lower levels of urinary sodium and potassium than the normal control group. Histopathological examination revealed the presence of refractile crystals in the tubular epithelial cell and damage to proximal tubular epithelium in the toxicant group but not in the SPP treatment groups. Treatment of SPP at 700 and 1,000 mg/kg significantly (p < 0.001 vs toxicant) lowered urinary calcium, serum creatinine, blood urea, and lipid peroxidation in urolithiatic rats, 21 days after induction of urolithiasis compared to the toxicant group. A long-term oral toxicity study revealed the normal growth of animals without any significant change in hematological, hepatic, and renal parameters; there was no evidence of abnormal histology of the heart, kidney, liver, spleen, or stomach tissues. These results suggest the usefulness of SPP as an antiurolithiatic and an antioxidant agent, and long-term daily oral consumption of SPP was found to be safe in albino Wistar rats for up to 3 months. Thus, SPP may be safe for clinical use as an antiurolithiatic formulation.

Matched MeSH terms: Epithelial Cells
Metabolic role of fatty acid binding protein 7 in mediating triple-negative breast cancer cell death via PPAR-α signaling

Kwong SC, Jamil AHA, Rhodes A, Taib NA, Chung I

J Lipid Res, 2019 11;60(11):1807-1817.
PMID: 31484694 DOI: 10.1194/jlr.M092379

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, partly due to the lack of targeted therapy available. Cancer cells heavily reprogram their metabolism and acquire metabolic plasticity to satisfy the high-energy demand due to uncontrolled proliferation. Accumulating evidence shows that deregulated lipid metabolism affects cancer cell survival, and therefore we sought to understand the function of fatty acid binding protein 7 (FABP7), which is expressed predominantly in TNBC tissues. As FABP7 was not detected in the TNBC cell lines tested, Hs578T and MDA-MB-231 cells were transduced with lentiviral particles containing either FABP7 open reading frame or red fluorescent protein. During serum starvation, when lipids were significantly reduced, FABP7 decreased the viability of Hs578T, but not of MDA-MB-231, cells. FABP7-overexpressing Hs578T (Hs-FABP7) cells failed to efficiently utilize other available bioenergetic substrates such as glucose to sustain ATP production, which led to S/G2 phase arrest and cell death. We further showed that this metabolic phenotype was mediated by PPAR-α signaling, despite the lack of fatty acids in culture media, as Hs-FABP7 cells attempted to survive. This study provides imperative evidence of metabolic vulnerabilities driven by FABP7 via PPAR-α signaling.

Matched MeSH terms: Tumor Cells, Cultured
Edible Bird's Nest: The Functional Values of the Prized Animal-Based Bioproduct From Southeast Asia-A Review

Lee TH, Wani WA, Lee CH, Cheng KK, Shreaz S, Wong S, et al.

Front Pharmacol, 2021;12:626233.
PMID: 33953670 DOI: 10.3389/fphar.2021.626233

Edible Bird's Nest (EBN) is the most prized health delicacy among the Chinese population in the world. Although some scientific characterization and its bioactivities have been studied and researched, no lights have been shed on its actual composition or mechanism. The aim of this review paper is to address the advances of EBN as a therapeutic animal bioproduct, challenges and future perspectives of research involving EBN. The methodology of this review primarily involved a thorough search from the literature undertaken on Web of Science (WoS) using the keyword "edible bird nest". Other information were obtained from the field/market in Malaysia, one of the largest EBN-producing countries. This article collects and describes the publications related to EBN and its therapeutic with diverse functional values. EBN extracts display anti-aging effects, inhibition of influenza virus infection, alternative traditional medicine in athletes and cancer patients, corneal wound healing effects, stimulation of proliferation of human adipose-derived stem cells, potentiate of mitogenic response, epidermal growth factor-like activities, enhancement of bone strength and dermal thickness, eye care, neuroprotective and antioxidant effects. In-depth literature study based on scientific findings were carried out on EBN and its properties. More importantly, the future direction of EBN in research and development as health-promoting ingredients in food and the potential treatment of certain diseases have been outlined.

Matched MeSH terms: Stem Cells
Fulltext Case Series of Pancytopenia Secondary to Pernicious Anaemia

Low, Qin Jian, Hong, Eric Qiu Weng, Cheo Seng Wee

Borneo Journal of Medical Sciences, 2019;13(2):55-59.
MyJurnal

Pernicious anaemia is an autoimmune disorder where vitamin B12 deficiency is caused by autoantibodies that interfere with vitamin B12 absorption by targeting intrinsic factor or parietal cells or both. It is commonly associated with anaemia, rarely pancytopenia. Here we reported two cases of pancytopenia due to undiagnosed pernicious anaemia. First case was a 26-year-old man presented with lethargy and reduced effort tolerance, associated with postural giddiness and palpitation. Clinically, he was pale with no other findings. On blood investigations, the patient was diagnosed pancytopenia secondary to pernicious anaemia. He was treated with daily subcutaneous injection of vitamin B12 cyanocobalamin 1 mg for one week followed by weekly injection for a month and subsequently with lifelong monthly subcutaneous injection. After receiving 2 weeks of B12 replacement, his full blood count had normalized and his symptoms resolved. Second case was a 65-year-old man presented with yellowish discolouration of the eyes with lethargy. On examination, he was pale with jaundice. On blood investigations, the patient was diagnosed pancytopenia secondary to pernicious anaemia. He was started with intramuscular injection of 1000 mcg vitamin B12 replacement daily for one week followed by monthly for 6 months. After one week of B12 replacement, his full blood count had normalized. He was started on lifelong 3 monthly injections of vitamin B12 replacement and he remained symptom free. Patients with pernicious anaemia often present with general signs and symptoms which occur insidiously. It is important that early diagnosis is made to avoid harmful complications such as neuropsychiatric disorders.

Matched MeSH terms: Parietal Cells, Gastric
Fulltext Heterometrus Spinifer: An Untapped Source of Anti-Tumor Molecules

Soopramanien M, Khan NA, Ghimire A, Sagathevan K, Siddiqui R

Biology (Basel), 2020 Jul 02;9(7).
PMID: 32630812 DOI: 10.3390/biology9070150

Despite intensive research, cancer incidence and mortality continue to rise. Consequently, the necessity to develop effective anti-cancer therapy is apparent. We have recently shown that the gut bacteria of animals living in polluted environments, such as crocodiles, are a potential source of novel anti-tumor molecules. To extend this work to other resilient species, we investigated the anti-tumor effects of gut bacteria of Heterometrus spinifer (a scorpion). Bacteria from the feces and gut were isolated, identified and evaluated for their anti-tumor effects. Bacterial-conditioned media was prepared in Roswell Park Memorial Institute (RPMI) 1640 media, and cytotoxicity and growth inhibitory properties were examined against cervical (HeLa) cancer cells. Liquid chromatography-mass spectrometry (LC-MS) was conducted to establish the identity of the molecules. Eighteen bacteria species from the gut (HSG01-18) and ten bacteria species from feces (HSF01-10) were tested for anti-tumor effects. Bacterial-conditioned media from scorpion gut and feces exhibited significant growth inhibitory effects against HeLa cells of 66.9% and 83.8%, respectively. Microscopic analysis of cancer cells treated with conditioned media HSG12 and HSG16 revealed apoptosis-like effects. HSG12 was identified as Pseudomonas aeruginosa and HSG16 was identified as Bacillus subtilis. Both conditioned media exhibited 100% growth inhibitory effects versus a selection of cancer cells, comprising cervical, breast and prostate cancer cells. LC-MS indicated the presence of 72 and 38 compounds, detected from HSG12 and HSG16, respectively. Out of these compounds, 47 were successfully identified while the remainder were unidentified and are possibly novel. This study suggests that the fecal and gut microbiota of scorpions might possess molecules with anti-cancer properties, however, further intensive research is needed to assess these expectations.

Matched MeSH terms: HeLa Cells
Fulltext Proteins from Lignosus tigris with selective apoptotic cytotoxicity towards MCF7 cell line and suppresses MCF7-xenograft tumor growth

Kong BH, Teoh KH, Tan NH, Tan CS, Ng ST, Fung SY

PeerJ, 2020;8:e9650.
PMID: 32832273 DOI: 10.7717/peerj.9650

Background: Lignosus tigris, a recently discovered species of the unique Lignosus family, has been traditionally used by the indigenous communities in Peninsular Malaysia to treat various ailments and as an alternative medicine for cancer treatment. The L. tigris cultivar sclerotia (Ligno TG-K) was found to contain numerous bioactive compounds with beneficial biomedicinal properties and the sclerotial extract exhibited potent antioxidant activity. However, the anticancer property of the Ligno TG-K including in vitro and in vivo antitumor effects as well as its anticancer active compounds and the mechanisms has yet to be investigated.
Methods: The cytotoxicity of the Ligno TG-K against human breast (MCF7), prostate (PC3) and lung (A549) adenocarcinoma cell lines was evaluated using MTT cytotoxicity assay. The cytotoxic mechanisms of the active high molecular weight proteins (HMWp) fraction were investigated through detection of caspases activity and apoptotic-related proteins expression by Western blotting. The in vivo antitumor activity of the isolated HMWp was examined using MCF7 mouse xenograft model. Shotgun LC-MS/MS analysis was performed to identify the proteins in the HMWp.
Results and Discussion: Cold water extract of the sclerotia inhibited proliferation of MCF7, A549 and PC3 cells with IC50 ranged from 28.9 to 95.0 µg/mL. Bioassay guided fractionation of the extract revealed that HMWp exhibited selective cytotoxicity against MCF7 cells via induction of cellular apoptosis by the activation of extrinsic and intrinsic signaling pathways. HMWp activated expression of caspase-8 and -9 enzymes, and pro-apoptotic Bax protein whilst inhibiting expression of tumor survivor protein, Bcl-2. HMWp induced tumor-cell apoptosis and suppressed growth of tumor in MCF-7 xenograft mice. Lectins, serine proteases, RNase Gf29 and a 230NA deoxyribonuclease are the major cytotoxic proteins that accounted for 55.93% of the HMWp.
Conclusion: The findings from this study provided scientific evidences to support the traditional use of the L. tigris sclerotia for treatment of breast cancer. Several cytotoxic proteins with high abundance have been identified in the HMWp of the sclerotial extract and these proteins have potential to be developed into new anticancer agents or as adjunct cancer therapy.

Matched MeSH terms: MCF-7 Cells
Fulltext Electrosprayed Alginate Nanoparticles as CRISPR Plasmid DNA Delivery Carrier: Preparation, Optimization, and Characterization

Alallam B, Altahhan S, Taher M, Mohd Nasir MH, Doolaanea AA

Pharmaceuticals (Basel), 2020 Jul 22;13(8).
PMID: 32707857 DOI: 10.3390/ph13080158

Therapeutic gene editing is becoming more feasible with the emergence of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) system. However, the successful implementation of CRISPR/Cas9-based therapeutics requires a safe and efficient in vivo delivery of the CRISPR components, which remains challenging. This study presents successful preparation, optimization, and characterization of alginate nanoparticles (ALG NPs), loaded with two CRISPR plasmids, using electrospray technique. The aim of this delivery system is to edit a target gene in another plasmid (green fluorescent protein (GFP)). The effect of formulation and process variables were evaluated. CRISPR ALG NPs showed mean size and zeta potential of 228 nm and -4.42 mV, respectively. Over 99.0% encapsulation efficiency was achieved while preserving payload integrity. The presence of CRISPR plasmids in the ALG NPs was confirmed by Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy. The tests revealed that the nanoparticles were cytocompatible and successfully introduced the Cas9 transgene in HepG2 cells. Nanoparticles-transfected HepG2 was able to edit its target plasmid by introducing double-strand break (DSB) in GFP gene, indicating the bioactivity of CRISPR plasmids encapsulated in alginate nanoparticles. This suggests that this method is suitable for biomedical application in vitro or ex vivo. Future investigation of theses nanoparticles might result in nanocarrier suitable for in vivo delivery of CRISPR/Cas9 system.

Matched MeSH terms: Hep G2 Cells
Fulltext Structure Characterization and Biological Activity of 2-Arylbenzofurans from an Indonesian Plant, Sesbania grandiflora (L.) Pers

Noviany N, Samadi A, Yuliyan N, Hadi S, Aziz M, Purwitasari N, et al.

Phytochem Lett, 2020 Feb;35:211-215.
PMID: 32863985 DOI: 10.1016/j.phytol.2019.12.008

A new 2-arylbenzofuran, sesbagrandiflorain C (1), together with four known compounds, 2-(3,4-dihydroxy-2-methoxyphenyl)-4-hydroxy-6-methoxybenzofuran-3-carbaldehyde (2), 2-(4-hydroxy-2-methoxyphenyl)-5,6-dimethoxybenzofuran-3-carboxaldehyde (3), sesbagrandiflorain A (4) and sesbagrandiflorain B (5), have been isolated from the stem bark of an Indonesian plant, Sesbania grandiflora (L.) Pers. The chemical structure of compound 1 was elucidated by UV, IR, MS, and NMR spectroscopic techniques. The proton and carbon NMR resonances of 1 were also compared with the predicted chemical shifts obtained from DFT quantum mechanical calculations with Gaussian. None of the compounds showed antibacterial activity against Bacillus subtilis, Escherichia coli, Mycobacterium smegmatis, Pseudomonas aeruginosa, and Staphylococcus aureus in an agar diffusion assay. However, sesbagrandiflorains A (4) and B (5) exhibited moderate activity against Mycobacterium tuberculosis H37Rv. In addition, compounds 1 - 5 have moderate cytotoxicity against HeLa, HepG2, and MCF-7 cancer cell lines.

Matched MeSH terms: MCF-7 Cells
Understanding of the Role of Pretreatment Methods on Rapeseed Oil from the Perspective of Phenolic Compounds

Xu YJ, Jiang F, Song J, Yang X, Shu N, Yuan L, et al.

J Agric Food Chem, 2020 Aug 19;68(33):8847-8854.
PMID: 32806128 DOI: 10.1021/acs.jafc.0c03539

The thermal pretreatment of oilseed prior to oil extraction could increase the oil yield and improve the oil quality. Phenolic compounds are important antioxidants in rapeseed oil. In this study, we investigated the impact of thermal pretreatment method on the rapeseed oil based on phenolic compound levels. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis showed that the phenolic compound contents in the microwave-pretreated oil were higher than those in the oven- and infrared-treated oils. Sinapic acid (SA) and canolol (CA), which are the top two phenolic compounds in rapeseed oil, exerted well 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity with IC50 values of 8.45 and 8.80 μmol/L. The cell experiment uncovered that SA and CA have significant biological activities related to rapeseed oil quality, including increase of antioxidant enzymes superoxide dismutase (SOD), alleviation of reactive oxygen species (ROS), and cytotoxicity of HepG2 cells after the intake of excessive oleic acid. Further investigation indicated that SA and CA reduced cell apoptosis rate through Bax-Bcl-2-caspase-3 and p53-Bax-Bcl-2-caspase-3, respectively. Taken together, our findings suggest that microwave pretreatment is the best method to improve the content of phenolic compounds in rapeseed oil compared with oven and infrared pretreatments.

Matched MeSH terms: Hep G2 Cells
Fulltext Nutritional compositions, biological activities, and phytochemical contents of the edible bamboo shoot, Dendrocalamus asper, from Malaysia

Kong, C. K., Tan, Y. N., Chye, F. Y., Sit, N. W.

International Food Research Journal, 2020;27(3):546-556.
MyJurnal

The edible shoots of Dendrocalamus asper (family Poaceae) is an underutilised food. The
present work was conducted to evaluate the nutritional compositions, biological activities, and
phytochemical contents of the shoots of D. asper obtained from different regions of Malaysia,
Peninsular (DP) and East Malaysia (DS). The nutritional analysis was conducted using the
Official Methods of Analysis of the AOAC International. All minerals were quantified using
an inductively coupled plasma-mass spectrometer, except for potassium which was measured
using a flame atomic absorption spectrometer. Total phenolic content (TPC) was determined
using the Folin-Ciocalteu method. Antibacterial and antifungal activities were assayed using
a colourimetric broth microdilution method, while antioxidant activity was tested using DPPH
radical scavenging activity, ferric-reducing antioxidant power, and cellular antioxidant activity (CAA) assays. Enzyme inhibitory activities were examined using α-amylase and α-glucosidase. Both bamboo shoots (boiled at 100°C for 20 min) were high in moisture (> 93 g/100 g
FW), crude protein (> 21 g/100 g DW), and crude fibre contents (> 9 g/100 g DW), but low in
fat content (< 4 g/100 g DW). Potassium was the most abundant mineral at 205.67 and 203.83
µg/100 g DW of bamboo shoots of DP and DS, respectively. The extracts (hexane, ethyl
acetate, ethanol, and water) of both shoots showed stronger antifungal activity than antibacterial activity against selected human pathogens. All extracts of DP shoots demonstrated higher
CAA in HeLa cells and α-amylase inhibitory activity than that of DS shoots. In contrast, the
extracts of DS shoots exhibited stronger inhibition on α-glucosidase and contained higher
TPC than that of DP shoots. The D. asper shoots obtained from the Peninsular Malaysia and
East Malaysia contained different types of secondary metabolites which account for the differences in the biological activities. In conclusion, D. asper shoots have potential as a nutritional
and functional food.

Matched MeSH terms: HeLa Cells
Fulltext Primary plasma cell leukaemia in a 39-year-old man

Kasinathan G

BMJ Case Rep, 2020 Jul 23;13(7).
PMID: 32709663 DOI: 10.1136/bcr-2020-235543

Plasma cell leukaemia (PCL) is an aggressive haematological malignancy which is classified into primary (pPCL) and secondary PCL. A 39-year-old Indian man presented to the Department of Hematology with a 2-week history of fever and lethargy. Clinically, he was pale and febrile. Haemogram revealed bicytopenia with leucocytosis. The peripheral blood film portrayed rouleax formation with 45% of circulating plasma cells. Serum protein electrophoresis and immunofixation revealed IgG lambda paraproteinaemia of 48 g/L. Bone marrow aspirate, flow cytometry and trephine were consistent with IgG lambda pPCL. He was treated with six cycles of bortezomib, thalidomide and dexamethasone combination chemotherapy followed by high-dose melphalan conditioning and autologous stem cell transplant. Currently, he is in complete remission for the past 18 months and is on oral lenalidomide maintenance therapy. Prognosis is often dismal in pPCL with the median overall survival below 1 year if treatment is delayed.

Matched MeSH terms: Plasma Cells
Scopoletin, an active principle of tree tobacco (Nicotiana glauca) inhibits human tumor vascularization in xenograft models and modulates ERK1, VEGF-A, and FGF-2 in computer model

Tabana YM, Hassan LE, Ahamed MB, Dahham SS, Iqbal MA, Saeed MA, et al.

Microvasc Res, 2016 09;107:17-33.
PMID: 27133199 DOI: 10.1016/j.mvr.2016.04.009

We recently reported the antineovascularization effect of scopoletin on rat aorta and identified its potential anti-angiogenic activity. Scopoletin could be useful as a systemic chemotherapeutic agent against angiogenesis-dependent malignancies if its antitumorigenic activity is investigated and scientifically proven using a suitable human tumor xenograft model. In the present study, bioassay-guided (anti-angiogenesis) phytochemical investigation was conducted on Nicotiana glauca extract which led to the isolation of scopoletin. Further, anti-angiogenic activity of scopoletin was characterized using ex vivo, in vivo and in silico angiogenesis models. Finally, the antitumorigenic efficacy of scopoletin was studied in human colorectal tumor xenograft model using athymic nude mice. For the first time, an in vivo anticancer activity of scopoletin was reported and characterized using xenograft models. Scopoletin caused significant suppression of sprouting of microvessels in rat aortic explants with IC50 (median inhibitory concentration) 0.06μM. Scopoletin (100 and 200mg/kg) strongly inhibited (59.72 and 89.4%, respectively) vascularization in matrigel plugs implanted in nude mice. In the tumor xenograft model, scopoletin showed remarkable inhibition on tumor growth (34.2 and 94.7% at 100 and 200mg/kg, respectively). Tumor histology revealed drastic reduction of the extent of vascularization. Further, immunostaining of CD31 and NG2 receptors in the histological sections confirmed the antivascular effect of scopoletin in tumor vasculature. In computer modeling, scopoletin showed strong ligand affinity and binding energies toward the following angiogenic factors: protein kinase (ERK1), vascular endothelial growth factor A (VEGF-A), and fibroblast growth factor 2 (FGF-2). These results suggest that the antitumor activity of scopoletin may be due to its strong anti-angiogenic effect, which may be mediated by its effective inhibition of ERK1, VEGF-A, and FGF-2.

Matched MeSH terms: HCT116 Cells; Human Umbilical Vein Endothelial Cells/drug effects; Human Umbilical Vein Endothelial Cells/metabolism
Intrauterine Gardnerella vaginalis Infection Results in Fetal Growth Restriction and Alveolar Septal Hypertrophy in a Rabbit Model

Cheah FC, Lai CH, Tan GC, Swaminathan A, Wong KK, Wong YP, et al.

Front Pediatr, 2020;8:593802.
PMID: 33553066 DOI: 10.3389/fped.2020.593802

Background:Gardnerella vaginalis (GV) is most frequently associated with bacterial vaginosis and is the second most common etiology causing intrauterine infection after Ureaplasma urealyticum. Intrauterine GV infection adversely affects pregnancy outcomes, resulting in preterm birth, fetal growth restriction, and neonatal pneumonia. The knowledge of how GV exerts its effects is limited. We developed an in vivo animal model to study its effects on fetal development. Materials and Methods: A survival mini-laparotomy was conducted on New Zealand rabbits on gestational day 21 (28 weeks of human pregnancy). In each dam, fetuses in the right uterine horn received intra-amniotic 0.5 × 102 colony-forming units of GV injections each, while their littermate controls in the left horn received sterile saline injections. A second laparotomy was performed seven days later. Assessment of the fetal pups, histopathology of the placenta and histomorphometric examination of the fetal lung tissues was done. Results: Three dams with a combined total of 12 fetuses were exposed to intra-amniotic GV, and 9 fetuses were unexposed. The weights of fetuses, placenta, and fetal lung were significantly lower in the GV group than the saline-inoculated control group [mean gross weight, GV (19.8 ± 3.8 g) vs. control (27.9 ± 1.7 g), p < 0.001; mean placenta weight, GV (5.5 ± 1.0 g) vs. control (6.5 ± 0.7 g), p = 0.027; mean fetal lung weight, GV (0.59 ± 0.11 g) vs. control (0.91 ± 0.08 g), p = 0.002. There was a two-fold increase in the multinucleated syncytiotrophoblasts in the placenta of the GV group than their littermate controls (82.9 ± 14.9 vs. 41.6 ± 13.4, p < 0.001). The mean alveolar septae of GV fetuses was significantly thicker than the control (14.8 ± 2.8 μm vs. 12.4 ± 3.8 μm, p = 0.007). Correspondingly, the proliferative index in the interalveolar septum was 1.8-fold higher in the GV group than controls (24.9 ± 6.6% vs. 14.2 ± 2.9%, p = 0.011). The number of alveoli and alveolar surface area did not vary between groups. Discussion: Low-dose intra-amniotic GV injection induces fetal growth restriction, increased placental multinucleated syncytiotrophoblasts and fetal lung re-modeling characterized by alveolar septal hypertrophy with cellular proliferative changes. Conclusion: This intra-amniotic model could be utilized in future studies to elucidate the acute and chronic effects of GV intrauterine infections.

Matched MeSH terms: Stem Cells
Synthesis and antileishmanial activity of fluorinated rhodacyanine analogues: The 'fluorine-walk' analysis

Lasing T, Phumee A, Siriyasatien P, Chitchak K, Vanalabhpatana P, Mak KK, et al.

Bioorg Med Chem, 2020 01 01;28(1):115187.
PMID: 31761725 DOI: 10.1016/j.bmc.2019.115187

In a search for potent antileishmanial drug candidates, eighteen rhodacyanine analogues bearing fluorine or perfluoroalkyl substituents at various positions were synthesized. These compounds were tested for their inhibitory activities against Leishmania martiniquensis and L. orientalis. This 'fluorine-walk' analysis revealed that the introduction of fluorine atom at C-5, 6, 5', or 6' on the benzothiazole units led to significant enhancement of the activity, correlating with the less negative reduction potentials of the fluorinated analogues confirmed by the electrochemical study. On the other hand, CF3 and OCF3 groups were found to have detrimental effects, which agreed with the poor aqueous solubility predicted by the in silico ADMET analysis. In addition, some of the analogues including the difluorinated species showed exceptional potency against the promastigote and axenic amastigote stages (IC50 = 40-85 nM), with the activities surpassing both amphotericin B and miltefosine.

Matched MeSH terms: Cells, Cultured
Conodiparines A-D, new bisindoles from Tabernaemontana. Reversal of vincristine-resistance with cultured cells

Kam TS, Sim KM, Koyano T, Toyoshima M, Hayashi M, Komiyama K

Bioorg Med Chem Lett, 1998 Jul 07;8(13):1693-6.
PMID: 9873417

Four new bisindoles of the vobasine-iboga type, conodiparines A-D were obtained from Tabernaemontana corymbosa which showed appreciable activity in reversing resistance in vincristine-resistant KB cells.

Matched MeSH terms: Tumor Cells, Cultured

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