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γ-Synuclein confers both pro-invasive and doxorubicin-mediated pro-apoptotic properties to the colon adenocarcinoma LS 174T cell line

Goh KW, Say YH

Tumour Biol., 2015 Sep;36(10):7947-60.
PMID: 25956278 DOI: 10.1007/s13277-015-3455-6

γ-synuclein, a neuronal protein of the synuclein family, is involved in carcinogenesis. To investigate its role in colorectal cancer carcinogenesis, we overexpressed γ-synuclein in LS 174T colon adenocarcinoma cell line (termed LS 174T-γsyn). When compared with untransfected/mock transfectants, LS 174T-γsyn had higher mobility in scratch wound assay, tend to scatter more in cell-scattering assay, and had enhanced lamellipodia and filopodia formation in cell-spreading assay. Enhanced adhesion of LS 174T-γsyn to fibronectin and collagen and significantly higher proliferation rate showed that γ-synuclein was able to increase extracellular matrix interaction and promoted proliferation of LS 174T. Higher invasiveness of LS 174T-γsyn was evidenced by enhanced invasion to the bottom of the basement membrane in Boyden chamber assay. However, LS 174T-γsyn were significantly more vulnerable to doxorubicin, vincristine and hydrogen peroxide insults, via apoptotic cell death. LS 174T-γsyn also had reduced anchorage-independent growth as shown by reduced colony formation and reduced anoikis resistance. We found that overexpression of γ-synuclein confers both pro-invasive and doxorubicin-mediated pro-apoptotic properties to LS 174T, where the former was mediated through enhanced cyclic adenosine monophosphate response element binding protein (CREB) phosphorylation, while the latter involved hepatocyte growth factor (HGF) downregulation and subsequent downstream signalling pathways possibly involving extracellular signal-regulated kinases (ERK)1/2, p38α, c-Jun N-terminal kinase (JNK) pan and Signal Transducers and Activators of Transcription (STATs). This unexpected contrasting finding as compared to other similar studies on colon cancer cell lines might be correlated with the degree of tumour advancement from which the cell lines were derived from.
Pattern of biopsy-proven renal disease in Sabah: A retrospective cross-sectional study over 3.5 years

Lee AV, Pang HC, Linus Lojikip S, Wong KW, Goh KW, Chan FS

Med J Malaysia, 2020 03;75(2):152-157.
PMID: 32281597

OBJECTIVES: To explore the epidemiological and histopathological patterns of glomerular diseases in Sabah.
METHODS: A state-wide cross-sectional study was conducted. There were 336 native renal biopsies in 296 eligible patients from 1st January 2013 to 30th June 2016. All patients aged ≥12 years with sufficient sampling (≥8 glomeruli) for histopathological assessment were included. Graft kidney biopsies, protocol-based biopsies and patients with uncertain demographics were excluded. Demographics of patients, clinical data, laboratory parameters prior to biopsy, and histology findings of renal biopsies were collected from local unit database and recorded into a standardised data collection form. Descriptive statistical analyses were employed and factors associated with Lupus nephritis (LN) were explored using logistic regression.
RESULTS: The mean age during biopsy was 34.53 years (Standard Deviation 0.759). Primary glomerulonephritis (PGN) accounted for 42.6% (126) of all native renal biopsies. The commonest cause of PGN was minimal change disease (38.9%, 49) followed by focal segmental glomerulosclerosis (33.3%, 42) and IgA nephropathy (14.3%, 18). LN is the leading cause for secondary glomerulonephritis (SGN) (87.2%, 136). Younger age (Odds Ratio, OR 0.978; 95% Confidence Interval, 95%CI 0.960, 0.996); female gender (OR 17.53; p<0.001); significant proteinuria (OR 132.0; p<0.001); creatinine level at biopsy (OR 11.26; p=0.004); positive antinuclear antibody (ANA) (OR 46.7; p<0.001); and ANA patterns (OR 8.038; p=0.018) were significant in predicting the odds of having LN.
CONCLUSION: This is the first epidemiology study of glomerular diseases in Sabah. The predominance of LN suggests lower threshold for renal biopsy in patients with suspected glomerular disorders. We have identified significant predictors for early detection and treatment of LN.
Fulltext Newly diagnosed end stage kidney disease in a single centre in Sabah

Wong KW, Lojikip S, Chan FS, Goh KW, Pang HC

Med J Malaysia, 2017 06;72(3):179-185.
PMID: 28733566 MyJurnal

AIM: To study the epidemiology, clinical characteristics, vascular access, and the short term survival of ESRD patients initiated on dialysis from Hospital Queen Elizabeth (HQE).

BACKGROUND: The number of patients with ESRD is increasing in Sabah, Malaysia. Most patients present late and some live in remote areas with difficult access to healthcare services. Many therefore present with potentially fatal complications.

METHODS: All the newly confirmed ESRD patients who were initiated on renal replacement therapy (RRT) from 1 January to 31 December 2014 were included. The basic epidemiological and clinical data were collected. They were divided into three groups: Group 1 - those known to the medical service and had been prepared properly for the initiation of RRT; Group 2 - those known to the medical service, but were not prepared for the RRT; Group 3 - those with undiagnosed CKD. Outcome is mainly survival at 3rd, 6th, 9th and 12th month.

RESULTS: There were 249 ESRD patients. 153 (61.4%) were male. The average age was 53.3 (range 12 - 83). The main cause of ESRD was diabetic nephropathy (128 patients, 51.4%). Most patients were started on RRT with a catheter (74.3%), 47 patients (18.9%) with a fistula, and 17 patients (6.8%) with a Tenckhoff catheter. 185 (74.3%) patients were not prepared properly (Group 2 - 66.3%, and Group 3 - 8.0%). The survival for 249 patients were 86.3% at 6 months, 77.9% at 12 months. Group 2 has the worst survival (81.9% at 6 months, 71.1% at 12 months).

CONCLUSIONS: Our data showed that most patients (74.3%) were started on dialysis in an unplanned manner with poor survival. A comprehensive and well-supported predialysis programme is needed.
A prospective study of incidence and outcome of acute kidney injury among hospitalised patients in Malaysia (My-AKI)

Goh CY, Visvanathan R, Leong CT, Hooi LS, Ch'ng CC, Yee SY, et al.

Med J Malaysia, 2023 Nov;78(6):733-742.
PMID: 38031214

INTRODUCTION: The incidence of acute kidney injury (AKI) among hospitalised patients has not been well studied in Malaysia.
MATERIALS AND METHODS: We conducted a prospective, multicentre study in seven hospitals in West Malaysia. All the adults admitted in March 2017 fulfilling Kidney Disease Improving Global Outcomes (KDIGO) criteria for AKI were included.
RESULTS: Of the 34,204 patients screened, 2,457 developed AKI (7.18%), 13.1% of which occurred in intensive care unit (ICU). There were 60.2% males with a mean age of 57.8 (±17.5) years. The most common comorbidities were hypertension (55.0%), diabetes (46.6%), ischaemic heart disease (15.1%) and chronic kidney disease (12.0%). The commonest causes of AKI were sepsis (41.7%), pre-renal (24.2%) and cardiorenal syndrome (10.8%). Nephrotoxin exposure was reported in 31%. At diagnosis, the proportion of AKI stages 1, 2 and 3 were 79.1%, 9.7%, 11.2%, respectively. Referral to nephrologists was reported in 16.5%. Dialysis was required in 176 (7.2%) patients and 55.6% were performed in the ICU. Acidosis (46.2%), uraemia (31.6%) and electrolyte disturbance (11.1%) were the commonest indications. Continuous renal replacement therapy (CRRT) was required in 14%. The average length of hospital stay was 9.5 days. In-hospital mortality was 16.4%. Among survivors, full and partial renal recovery was seen in 74.7% and 16.4% respectively while 8.9% failed to recover. After a mean follow-up of 13.7 months, 593 (30.2%) of survivors died and 38 (1.9%) initiated chronic dialysis. Mortality was highest among those with malignancies (Hazard Ratio, HR 2.14), chronic liver disease (HR 2.13), neurological disease (HR 1.56) and cardiovascular disease (HR 1.17).
CONCLUSION: AKI is common in hospitalised patients and is with associated high mortality during and after hospitalisation.
Fulltext Proximate composition, lipid and elemental profiling of eight varieties of avocado (Persea americana)

Nasri C, Halabi Y, Hajib A, Choukri H, Harhar H, Lee LH, et al.

Sci Rep, 2023 Dec 20;13(1):22767.
PMID: 38123687 DOI: 10.1038/s41598-023-50119-y

Eight Moroccan avocado varieties were analyzed for their nutritional composition and physicochemical properties. The nutritional contents of the sample were determined through the evaluation of the moisture, oil, ash, protein, and carbohydrate contents, and energy value calculation. Additionally, macroelements (Ca, Mg, and Na) and microelements (Fe, Zn, Cu, and Mn) were determined in the mineral profile. Oils were examined also for their fatty acid, phytosterol, and tocopherol profiles. As a result of the study, the avocado presents significant differences between the eight studied varieties (p
Fulltext Design of three-component essential oil extract mixture from Cymbopogon flexuosus, Carum carvi, and Acorus calamus with enhanced antioxidant activity

Assaggaf H, Jeddi M, Mrabti HN, Ez-Zoubi A, Qasem A, Attar A, et al.

Sci Rep, 2024 Apr 22;14(1):9195.
PMID: 38649707 DOI: 10.1038/s41598-024-59708-x

The development of novel antioxidant compounds with high efficacy and low toxicity is of utmost importance in the medicine and food industries. Moreover, with increasing concerns about the safety of synthetic components, scientists are beginning to search for natural sources of antioxidants, especially essential oils (EOs). The combination of EOs may produce a higher scavenging profile than a single oil due to better chemical diversity in the mixture. Therefore, this exploratory study aims to assess the antioxidant activity of three EOs extracted from Cymbopogon flexuosus, Carum carvi, and Acorus calamus in individual and combined forms using the augmented-simplex design methodology. The in vitro antioxidant assays were performed using DPPH and ABTS radical scavenging approaches. The results of the Chromatography Gas-Mass spectrometry (CG-MS) characterization showed that citral (29.62%) and niral (27.32%) are the main components for C. flexuosus, while D-carvone (62.09%) and D-limonene (29.58%) are the most dominant substances in C. carvi. By contrast, β-asarone (69.11%) was identified as the principal component of A. calamus (30.2%). The individual EO exhibits variable scavenging activities against ABTS and DPPH radicals. These effects were enhanced through the mixture of the three EOs. The optimal antioxidant formulation consisted of 20% C. flexuosus, 53% C. carvi, and 27% A. calamus for DPPHIC50. Whereas 17% C. flexuosus, 43% C. carvi, and 40% A. calamus is the best combination leading to the highest scavenging activity against ABTS radical. These findings suggest a new research avenue for EOs combinations to be developed as novel natural formulations useful in food and biopharmaceutical products.
Fulltext Comparative analysis of potential drug-drug interactions in a public and private hospital among chronic kidney disease patients in Khyber Pakhtunkhwa: A retrospective cross-sectional study

Zafar R, Rehman IU, Shah Y, Ming LC, Goh HP, Goh KW

PLoS One, 2023;18(9):e0291417.
PMID: 37773947 DOI: 10.1371/journal.pone.0291417

INTRODUCTION: Chronic kidney disease (CKD) is a significant public health challenge due to its rising incidence, mortality, and morbidity. Patients with kidney diseases often suffer from various comorbid conditions, making them susceptible to potential drug-drug interactions (pDDIs) due to polypharmacy and multiple prescribers. Inappropriate prescriptions for CKD patients and their consequences in the form of pDDIs are a major challenge in Pakistan.
AIM: This study aimed to compare the incidence and associated risk factors of pDDIs among a public and private sector hospital in Khyber Pakhtunkhwa, Pakistan.
METHOD: A retrospective cross-sectional study design was conducted to compare pDDIs among public and private sector hospitals from January 2023 to February 2023. Patients profile data for the full year starting from January 1 2022 to December 302022, was accessed All adult patients aged 18 years and above, of both genders, who currently have or have previously been diagnosed with end-stage renal disease (ESRD) were included. For assessing pDDIs, patient data was retrieved and checked using Lexicomp UpToDate® for severity and documentation of potential drug-drug interactions.
RESULTS: A total of 358 patients' data was retrieved (with n = 179 in each hospital); however, due to incomplete data, n = 4 patients were excluded from the final analysis. The prevalence of pDDIs was found to be significantly higher in private hospitals (84.7%) than in public hospitals (26.6%), with a p-value <0.001. Patients in the age category of 41-60 years (AOR = 6.2; p = 0.008) and those prescribed a higher number of drugs (AOR = 1.2; p = 0.027) were independently associated with pDDIs in private hospitals, while the higher number of prescribed drugs (AOR = 2.9; p = <0.001) was an independent risk factor for pDDIs in public hospitals. The majority of pDDIs (79.0%) were of moderate severity, and a significant number of patients (15.1%) also experienced major pDDIs, with a p-value <0.001. The majority of pDDIs had fair documentation for reliability rating in both public and private hospitals.
CONCLUSION: The prevalence of pDDIs was higher among CKD patients at private hospitals, and most of the pDDIs were of moderate severity. A considerable number of patients also experienced major pDDIs. The risk of experiencing pDDIs was found to be higher in older patients and among those prescribed a higher number of drugs.
Fulltext Cellular prion protein and γ-synuclein overexpression in LS 174T colorectal cancer cell drives endothelial proliferation-to-differentiation switch

Ong SH, Goh KW, Chieng CK, Say YH

PeerJ, 2018;6:e4506.
PMID: 29527422 DOI: 10.7717/peerj.4506

Background: Tumor-induced angiogenesis is an imperative event in pledging new vasculature for tumor metastasis. Since overexpression of neuronal proteins gamma-synuclein (γ-Syn) and cellular prion protein (PrPC) is always detected in advanced stages of cancer diseases which involve metastasis, this study aimed to investigate whether γ-Syn or PrPCoverexpression in colorectal adenocarcinoma, LS 174T cells affects angiogenesis of endothelial cells, EA.hy 926 (EA).
Methods: EA cells were treated with conditioned media (CM) of LS 174T-γ-Syn or LS 174T-PrP, and their proliferation, invasion, migration, adhesion and ability to form angiogenic tubes were assessed using a range of biological assays. To investigate plausible background mechanisms in conferring the properties of EA cells above, nitrite oxide (NO) levels were measured and the expression of angiogenesis-related factors was assessed using a human angiogenesis antibody array.
Results: EA proliferation was significantly inhibited by LS 174T-PrP CM whereas its telomerase activity was reduced by CM of LS 174T-γ-Syn or LS 174T-PrP, as compared to EA incubated with LS 174T CM. Besides, LS 174T-γ-Syn CM or LS 174T-PrP CM inhibited EA invasion and migration in Boyden chamber assay. Furthermore, LS 174T-γ-Syn CM significantly inhibited EA migration in scratch wound assay. Gelatin zymography revealed reduced secretion of MMP-2 and MMP-9 by EA treated with LS 174T-γ-Syn CM or LS 174T-PrP CM. In addition, cell adhesion assay showed lesser LS 174T-γ-Syn or LS 174T-PrP cells adhered onto EA, as compared to LS 174T. In tube formation assay, LS 174T-γ-Syn CM or LS 174T-PrP CM induced EA tube formation. Increased NO secretion by EA treated with LS 174T-γ-Syn CM or LS 174T-PrP CM was also detected. Lastly, decreased expression of pro-angiogenic factors like CXCL16, IGFBP-2 and amphiregulin in LS 174T-γ-Syn CM or LS 174T-PrP CM was detected using the angiogenesis antibody array.
Discussion: These results suggest that overexpression of γ-Syn or PrPCcould possibly be involved in colorectal cancer-induced angiogenesis by inducing an endothelial proliferation-differentiation switch. NO could be the main factor in governing this switch, and modulation on the secretion patterns of angiogenesis-related proteins could be the strategy of colorectal cancer cells overexpressing γ-Syn or PrPCin ensuring this transition.
Saussurea costus (Falc.) Lipsch.: a comprehensive review of its pharmacology, phytochemicals, ethnobotanical uses, and therapeutic potential

Kumari R, Negi M, Thakur P, Mahajan H, Raina K, Sharma R, et al.

Naunyn Schmiedebergs Arch Pharmacol, 2024 Mar;397(3):1505-1524.
PMID: 37755516 DOI: 10.1007/s00210-023-02694-0

Saussurea costus (Falc.) Lipsch., commonly known as costus, is a perennial herb that has been traditionally used in various indigenous medicinal systems across Asia. Its historical prominence in traditional remedies underscores the need to explore its phytochemical composition, pharmacological properties, and potential therapeutic benefits. This review aims to provide a comprehensive overview of the available literature on the pharmacological properties, phytochemical constituents, ethnobotanical uses, and therapeutic potential of S. costus. An exhaustive search was performed across multiple electronic databases, including PubMed/MedLine, Google Scholar, Web of Science, Scopus, TRIP database, and Science Direct. Both experimental and clinical studies, as well as traditional ethnobotanical records, were considered for inclusion. The phytochemical analysis revealed that S. costus contains a plethora of bioactive compounds, including sesquiterpenes, flavonoids, and essential oils, which are responsible for its myriad of medicinal properties. The pharmacological studies have demonstrated its anti-inflammatory, anti-oxidant, anti-cancer, hepatoprotective, and immunomodulatory effects, among others. Ethnobotanical data showcased its extensive use in treating ailments like asthma, digestive disorders, and skin conditions. Some clinical trials also underscore its efficacy in certain health conditions, corroborating its traditional uses. S. costus possesses significant therapeutic potential, largely attributable to its rich phytochemical composition; the convergence of its traditional uses and modern pharmacological findings suggests promising avenues for future research, especially in drug development and understanding its mechanism of action in various ailments.
Fulltext Variations in Antioxidant Capacity, Oxidative Stability, and Physicochemical Quality Parameters of Walnut (Juglans regia) Oil with Roasting and Accelerated Storage Conditions

Elouafy Y, El Idrissi ZL, El Yadini A, Harhar H, Alshahrani MM, Al Awadh AA, et al.

Molecules, 2022 Nov 09;27(22).
PMID: 36431794 DOI: 10.3390/molecules27227693

Walnut oil, like all vegetable oils, is chemically unstable because of the sensitivity of its unsaturated fatty acids to the oxidation phenomenon. This phenomenon is based on a succession of chemical reactions, under the influence of temperature or storage conditions, that always lead to a considerable change in the quality of the oil by promoting the oxidation of unsaturated fatty acids through the degradation of their C-C double bonds, leading to the formation of secondary oxidation products that reduce the nutritional values of the oil. This research examines the oxidative stability of roasted and unroasted cold-pressed walnut oils under accelerated storage conditions. The oxidative stability of both oils was evaluated using physicochemical parameters: chemical composition (fatty acids, phytosterols, and tocopherols), pigment content (chlorophyll and carotenoids), specific extinction coefficients (K232 and K270), and quality indicators (acid and peroxide value) as well as the evaluation of radical scavenging activity by the DPPH method. The changes in these parameters were evaluated within 60 days at 60 ± 2 °C. The results showed that the levels of total phytosterols, the parameters of the acid and peroxide value, K232 and K270, increased slightly for both oils as well as the total tocopherol content and the antioxidant activity affected by the roasting process. In contrast, the fatty acid profiles did not change considerably during the 60 days of our study. After two months of oil treatment at 60 °C, the studied oils still showed an excellent physicochemical profile, which allows us to conclude that these oils are stable and can withstand such conditions. This may be due to the considerable content of tocopherols (vitamin E), which acts as an antioxidant.
Fulltext Effects of Extraction Methods on the Bioactivities and Nutritional Value of Virginia and Valencia-Type Peanut Oil

Idrissi ZLE, El Moudden H, Mghazli N, Bouyahya A, Guezzane CE, Alshahrani MM, et al.

Molecules, 2022 Nov 09;27(22).
PMID: 36431807 DOI: 10.3390/molecules27227709

This study aimed to evaluate the effects of peanut varieties cultivated in Morocco (Virginia and Valencia) and extraction methods (cold press, CP; Soxhlet, Sox and maceration, and Mac) on the fatty acid profile, phytosterol, and tocopherol contents, quality characteristics, and antioxidant potential of peanut seed oil. The DPPH method was used to determine the antioxidant activity of the oils. The results revealed that fatty acid content was slightly affected by the extraction technique. However, the CP method was shown to be an excellent approach for extracting oil with desirable quality features compared to the Sox and Mac methods. Furthermore, the peanut oil extracted via CP carried a higher amount of bioactive compounds and exhibited remarkable antioxidant activities. The findings also revealed higher oleic acid levels from the Virginia oil, ranging from 56.46% to 56.99%. Besides, a higher total phytosterol and tocopherol content and DPPH scavenging capacity were obtained from the Valencia oil. Analyzing the study, it can be inferred that extraction method and variety both affect the composition of the peanut oil's bioactive compounds and antioxidant activity. This information is relevant for extracting peanut oil with a greater level of compounds of industrial interest.
Fulltext In Vitro Influence of ZnO, CrZnO, RuZnO, and BaZnO Nanomaterials on Bacterial Growth

Abdallah EM, Modwi A, Al-Mijalli SH, Mohammed AE, Idriss H, Omar AS, et al.

Molecules, 2022 Nov 28;27(23).
PMID: 36500402 DOI: 10.3390/molecules27238309

In this work, ZnO, CrZnO, RuZnO, and BaZnO nanomaterials were synthesized and characterized in order to study their antibacterial activity. The agar well diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays were used to determine the antibacterial activity of the fabricated nanomaterials against Staphylococcus aureus ATCC 29213, Escherichia coli ATCC35218, Klebsiella pneumoniae ATCC 7000603, and Pseudomonas aeruginosa ATCC 278533. The well-diffusion test revealed significant antibacterial activity against all investigated bacteria when compared to vancomycin at a concentration of 1 mg/mL. The most susceptible bacteria to BaZnO, RuZnO, and CrZnO were Staphylococcus aureus (15.5 ± 0.5 mm), Pseudomonas aeruginosa (19.2 ± 0.5 mm), and Pseudomonas aeruginosa (19.7 ± 0.5), respectively. The MIC values indicated that they were in the range of 0.02 to 0.2 mg/mL. The MBC values showed that the tested bacteria's growth could be inhibited at concentrations ranging from 0.2 to 2.0 mg/mL. According to the MBC/MIC ratio, BaZnO, RuZnO, and CrZnO exhibit bacteriostatic effects and may target bacterial protein synthesis based on the results of the tolerance test. This study shows the efficacy of the above-mentioned nanoparticles on bacterial growth. Further biotechnological and toxicological studies on the nanoparticles fabricated here are recommended to benefit from these findings.
Fulltext A Comprehensive Review of the Pharmacological Properties and Bioactive Components of Retama monosperma

El Yadini A, Elouafy Y, Amiri-Ardekani E, Shafiee M, Firouzi A, Sasani N, et al.

Molecules, 2023 Feb 10;28(4).
PMID: 36838696 DOI: 10.3390/molecules28041708

Retama monosperma L. (Boiss.) or Genista monosperma L. (Lam.), known locally as "R'tam", is a spontaneous and annual herb that belongs to the Fabaceae family. It is native to the Mediterranean regions, specifically in the desert areas and across the Middle Atlas in Morocco. This plant has been extensively used in folk medicine and it is rich in bioactive compounds, including polyphenols, flavonoids, and alkaloids. Current research efforts are focusing on the development of novel natural drugs as alternatives to various organic and non-organic chemical products from Retama monosperma. In addition, extract, and isolated compounds obtained from different parts of the chosen plant have been described to exhibit multiple biological and pharmacological properties such as antioxidant, anti-aging, anti-inflammatory, antihypertensive, anti-helminthic, disinfectant, diuretic, and hypoglycemic effects. The plant-derived extract also acts as an antimicrobial agent, which is highly efficient in the treatment of bacterial, viral, and fungal infections. Its antiproliferative effects are associated with some mechanisms, such as the inhibition of cell cycle arrest and apoptosis. In light of these assessments, we critically highlight the beneficial effects of the flowers, stems, seeds extracts, and isolated compounds from R. monosperma (L.) Boiss in human health care, industrial, and other applications, as well as the possible ways to be employed as a potential natural source for future drug discovery.
Fulltext Influence of the Extraction Method on the Quality and Chemical Composition of Walnut (Juglans regia L.) Oil

Elouafy Y, El Yadini A, El Moudden H, Harhar H, Alshahrani MM, Awadh AAA, et al.

Molecules, 2022 Nov 08;27(22).
PMID: 36431782 DOI: 10.3390/molecules27227681

The present study investigated and compared the quality and chemical composition of Moroccan walnut (Juglans regia L.) oil. This study used three extraction techniques: cold pressing (CP), soxhlet extraction (SE), and ultrasonic extraction (UE). The findings showed that soxhlet extraction gave a significantly higher oil yield compared to the other techniques used in this work (65.10% with p < 0.05), while cold pressing and ultrasonic extraction gave similar yields: 54.51% and 56.66%, respectively (p > 0.05). Chemical composition analysis was carried out by GC−MS and allowed 11 compounds to be identified, of which the major compound was linoleic acid (C18:2), with a similar percentage (between 57.08% and 57.84%) for the three extractions (p > 0.05). Regarding the carotenoid pigment, the extraction technique significantly affected its content (p < 0.05) with values between 10.11 mg/kg and 14.83 mg/kg. The chlorophyll pigment presented a similar content in both oils extracted by SE and UE (p > 0.05), 0.20 mg/kg and 0.16 mg/kg, respectively, while the lowest content was recorded in the cold-pressed oil with 0.13 mg/kg. Moreover, the analysis of phytosterols in walnut oil revealed significantly different contents (p < 0.05) for the three extraction techniques (between 1168.55 mg/kg and 1306.03 mg/kg). In addition, the analyses of tocopherol composition revealed that γ-tocopherol represented the main tocopherol isomer in all studied oils and the CP technique provided the highest content of total tocopherol with 857.65 mg/kg, followed by SE and UE with contents of 454.97 mg/kg and 146.31 mg/kg, respectively, which were significantly different (p < 0.05). This study presents essential information for producers of nutritional oils and, in particular, walnut oil; this information helps to select the appropriate method to produce walnut oil with the targeted quality properties and chemical compositions for the desired purpose. It also helps to form a scientific basis for further research on this plant in order to provide a vision for the possibility of exploiting these oils in the pharmaceutical, cosmetic, and food fields.
Fulltext Comparative Investigation of Chemical Constituents of Kernels, Leaves, Husk, and Bark of Juglans regia L., Using HPLC-DAD-ESI-MS/MS Analysis and Evaluation of Their Antioxidant, Antidiabetic, and Anti-Inflammatory Activities

Bourais I, Elmarrkechy S, Taha D, Badaoui B, Mourabit Y, Salhi N, et al.

Molecules, 2022 Dec 16;27(24).
PMID: 36558122 DOI: 10.3390/molecules27248989

Leaves, husk, kernels, and bark methanolic extracts of Juglans regia L. were tested for their in vitro antidiabetic, anti-inflammatory, and antioxidant activities. For these purposes, α-amylase and α-glucosidase were used as the main enzymes to evaluate antidiabetic activities. Moreover, lipoxidase and tyrosinase activities were tested to estimate anti-inflammatory properties. Antioxidant properties of Juglans regia L., extracts were determined using three different assays. Leaves extract has an important radical scavenging activity and a-amylase inhibition. Similarly, husk extracts showed high total phenolic content (306.36 ± 4.74 mg gallic acid equivalent/g dry extract) with an important α-amylase inhibition (IC50 = 75.42 ± 0.99 µg/mL). Kernels exhibit significant tyrosinase (IC50 = 51.38 ± 0.81 µg/mL) correlated with antioxidant activities (p < 0.05). Husk and bark extracts also showed strong anti-lipoxidase activities with IC50 equal to 29.48 ± 0.28 and 28.58 ± 0.35 µg/mL, respectively. HPLC-DAD-ESI-MS/MS analysis highlights the phenolic profile of methanolic extracts of Juglans regia L. plant parts. The identified polyphenols were known for their antioxidant, antidiabetic (dicaffeoyl-quinic acid glycoside in kernels), and anti-inflammatory (3,4-dihydroxybenzoic acid in leaves) activities. Further investigations are needed to determine molecular mechanisms involved in these effects as well as to study the properties of the main identified compounds.
Fulltext Mentha longifolia Essential Oil and Pulegone in Edible Coatings of Alginate and Chitosan: Effects on Pathogenic Bacteria in Lactic Cheese

Shahdadi F, Faryabi M, Khan H, Sardoei AS, Fazeli-Nasab B, Goh BH, et al.

Molecules, 2023 Jun 05;28(11).
PMID: 37299028 DOI: 10.3390/molecules28114554

Mentha longifolia is a valuable medicinal and aromatic plant that belongs to Lamiaceae family. This study looked at the antibacterial effects of M. longifolia essential oil and pulegone in edible coatings made of chitosan and alginate on the growth of Staphylococcus aureus, Listeria monocytogenes, and Escherichia coli in cheese. For this purpose, first fresh mint plant was collected from the cold region of Jiroft in Kerman province. Plant samples were dried in the shade at ambient temperature, and essential oil was prepared using Clevenger. The essential oil was analyzed by gas chromatography using mass spectrometric (GC/MS) detection. The major composition of M. longifolia oil was pulegone (26.07%), piperitone oxide (19.72%), and piperitone (11.88%). The results showed that adding M. longifolia essential oils and pulegone to edible coatings significantly reduced the growth of bacteria during storage. The bacterial population decreased by increasing the concentration of chitosan, M. longifolia, and pulegone in edible coatings. When the effects of pulegone and M. longifolia essential oils on bacteria were compared, it was found that pulegone had a stronger effect on bacterial population reduction. Coating treatments showed more antibacterial activity on E. coli than other bacteria. In general, the results of this research showed that alginate and chitosan coatings along with M. longifolia essential oil and its active ingredient pulegone had antibacterial effects against S. aureus, L. monocytogenes, and E. coli in cheese.
Fulltext Antioxidant, Volatile Compounds; Antimicrobial, Anti-Inflammatory, and Dermatoprotective Properties of Cedrus atlantica (Endl.) Manetti Ex Carriere Essential Oil: In Vitro and In Silico Investigations

El Hachlafi N, Mrabti HN, Al-Mijalli SH, Jeddi M, Abdallah EM, Benkhaira N, et al.

Molecules, 2023 Aug 06;28(15).
PMID: 37570883 DOI: 10.3390/molecules28155913

Cedrus atlantica (Endl.) Manetti ex Carriere is an endemic tree possessing valuable health benefits which has been widely used since time immemorial in international traditional pharmacopoeia. The aim of this exploratory investigation is to determine the volatile compounds of C. atlantica essential oils (CAEOs) and to examine their in vitro antimicrobial, antioxidant, anti-inflammatory, and dermatoprotective properties. In silico simulations, including molecular docking and pharmacokinetics absorption, distribution, metabolism, excretion, and toxicity (ADMET), and drug-likeness prediction were used to reveal the processes underlying in vitro biological properties. Gas chromatography-mass spectrophotometry (GC-MS) was used for the chemical screening of CAEO. The antioxidant activity of CAEO was investigated using four in vitro complementary techniques, including ABTS and DPPH radicals scavenging activity, ferric reductive power, and inhibition of lipid peroxidation (β-carotene test). Lipoxygenase (5-LOX) inhibition and tyrosinase inhibitory assays were used for testing the anti-inflammatory and dermatoprotective properties. GC-MS analysis indicated that the main components of CAEO are β-himachalene (28.99%), α-himachalene (14.43%), and longifolene (12.2%). An in vitro antimicrobial activity of CAEO was examined against eleven strains of Gram-positive bacteria (three strains), Gram-negative bacteria (four strains), and fungi (four strains). The results demonstrated high antibacterial and antifungal activity against ten of them (>15 mm zone of inhibition) using the disc-diffusion assay. The microdilution test showed that the lowest values of MIC and MBC were recorded with the Gram-positive bacteria in particular, which ranged from 0.0625 to 0.25 % v/v for MIC and from 0.5 to 0.125 % v/v for MBC. The MIC and MFC of the fungal strains ranged from 0.5 to 4.0% (MIC) and 0.5 to 8.0% v/v (MFC). According to the MBC/MIC and MFC/MIC ratios, CAEO has bactericidal and fungicidal activity. The results of the in vitro antioxidant assays revealed that CAEO possesses remarkable antioxidant activity. The inhibitory effects on 5-LOX and tyrosinase enzymes was also significant (p < 0.05). ADMET investigation suggests that the main compounds of CAEO possess favorable pharmacokinetic properties. These findings provide scientific validation of the traditional uses of this plant and suggest its potential application as natural drugs.
Fulltext Assessing the Protective Role of Epigallocatechin Gallate (EGCG) against Water-Pipe Smoke-Induced Toxicity: A Comparative Study on Gene Expression and Histopathology

Al-Awaida W, Goh KW, Al-Ameer HJ, Gushchina YS, Torshin VI, Severin AE, et al.

Molecules, 2023 Nov 09;28(22).
PMID: 38005223 DOI: 10.3390/molecules28227502

Exposure to water-pipe smoking, whether flavored or unflavored, has been shown to instigate inflammation and oxidative stress in BALB/c mice. This consequently results in alterations in the expression of inflammatory markers and antioxidant genes. This study aimed to scrutinize the impact of Epigallocatechin gallate (EGCG)-a key active component of green tea-on inflammation and oxidative stress in BALB/c mice exposed to water-pipe smoke. The experimental setup included a control group, a flavored water-pipe smoke (FWP) group, an unflavored water-pipe smoke (UFWP) group, and EGCG-treated flavored and unflavored groups (FWP + EGCG and UFWP + EGCG). Expression levels of IL-6, IL1B, TNF-α, CAT, GPXI, MT-I, MT-II, SOD-I, SOD-II, and SOD-III were evaluated in lung, liver, and kidney tissues. Histopathological changes were also assessed. The findings revealed that the EGCG-treated groups manifested a significant decline in the expression of inflammatory markers and antioxidant genes compared to the FWP and UFWP groups. This insinuates that EGCG holds the capacity to alleviate the damaging effects of water-pipe smoke-induced inflammation and oxidative stress. Moreover, enhancements in histopathological features were observed in the EGCG-treated groups, signifying a protective effect against tissue damage induced by water-pipe smoking. These results underscore the potential of EGCG as a protective agent against the adverse effects of water-pipe smoking. By curbing inflammation and oxidative stress, EGCG may aid in the prevention or mitigation of smoking-associated diseases.
Fulltext Stroke Patients' Characteristics and Clinical Outcomes: A Pre-Post COVID-19 Comparison Study

Loh HC, Neoh KK, Tang ASN, Chin CJ, Suppiah PD, Looi I, et al.

Medicina (Kaunas), 2021 May 19;57(5).
PMID: 34069433 DOI: 10.3390/medicina57050507

Background and Objectives: The Coronavirus disease 2019 (COVID-19) pandemic caused significant disruption to established medical care systems globally. Thus, this study was aimed to compare the admission and outcome variables such as number of patient and its severity, acute recanalisation therapy given pre-post COVID-19 at a primary stroke centre located in Malaysia. Methods: This cross-sectional hospital-based study included adult ischaemic stroke patients. Variables of the study included the number of ischaemic stroke patients, the proportions of recanalisation therapies, stroke severity during admission based on the National Institutes of Health Stroke Scale, functional outcome at discharge based on the modified Rankin Scale, and relevant workflow metrics. We compared the outcome between two six-month periods, namely the pre-COVID-19 period (March 2019 to September 2019) and the COVID-19 period (March 2020 to September 2020). Results: There were 131 and 156 patients, respectively, from the pre-COVID-19 period and the COVID-19 period. The median door-to-scan time and the median door-to-reperfusion time were both significantly shorter in the COVID-19 period (24.5 min versus 12.0 min, p = 0.047) and (93.5 min versus 60.0 min, p = 0.015), respectively. There were also significantly more patients who received intravenous thrombolysis (7.6% versus 17.3%, p = 0.015) and mechanical thrombectomy (0.8% versus 6.4%, p = 0.013) in the COVID-19 period, respectively. Conclusions: The COVID-19 pandemic may not have caused disruptions of acute stroke care in our primary stroke centre. Our data indicated that the number of ischaemic stroke events remained stable, with a significant increase of recanalisation therapies and better in-hospital workflow metrics during the COVID-19 pandemic period. However, we would like to highlight that the burden of COVID-19 cases in the study area was very low. Therefore, the study may not have captured the true burden (and relevant delays in stroke patient management) during the COVID-19 pandemic. The effect of the pandemic crisis is ongoing and both pre-hospital and in-hospital care systems must continue to provide optimal, highly time-dependent stroke care services.
Fulltext Prolonged Maternal Separation Reduces Anxiety State and Increases Compulsive Burying Activity in the Offspring of BALB/c Mice

Jarrar Q, Ayoub R, Alhussine K, Goh KW, Moshawih S, Ardianto C, et al.

J Pers Med, 2022 Nov 17;12(11).
PMID: 36422097 DOI: 10.3390/jpm12111921

BACKGROUND: The elevated plus maze (EPM) and the marble burying (MB) tests are common behavioral tests used for behavioral phenotyping in mouse models for neurodevelopmental disorders. However, the behavioral effects of maternal separation (MS), a standard paradigm for early life stress in animals, in both the EPM and MB tests remain incompletely known.
OBJECTIVES: This study aimed to investigate the behavioral effects of prolonged MS in the offspring of mice using the EPM and MB tests.
METHODS: Male BALB/c mice were isolated from their mothers for 4 h each day during the first 30 days after birth. On day 50 postnatal, groups of separated and non-separated mice (n = 18/each group) were subjected to the EPM and MB tests for comparative behavioral evaluations. In addition, the locomotor activity of mice was evaluated using the actophotometer test.
RESULTS: The findings of the EPM test revealed that separated mice exhibited anxiolytic-like behaviors, as evidenced by a significant increase in the latency to closed arms and the time spent in the open arms compared with non-separated mice. Separated mice also showed compulsive burying activity in the MB test, as determined by a significant increase in the number of buried marbles. The results of the actophotometer test did not show any significant change in locomotor activity.
CONCLUSIONS: Prolonged MS caused the adult offspring of mice to exhibit a decrease in anxiety state and increased compulsive burying activity, which were not associated with a change in locomotor activity. Further investigations with validated tests are needed to support these findings.

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