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Cytokine storm and neuropathological alterations in patients with neurological manifestations of COVID-19

Tsagkaris C, Bilal M, Aktar I, Aboufandi Y, Tas A, Aborode AT, et al.

Curr Alzheimer Res, 2022 Sep 08.
PMID: 36089786 DOI: 10.2174/1567205019666220908084559

The COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), a respiratory pathogen with neuroinvasive potential. Neurological COVID-19 manifestations include loss of smell and taste, headache, dizziness, stroke, and potentially fatal encephalitis. Several studies found elevated proinflammatory cytokines such as TNF-α, IFN-γ, IL-6 IL-8, IL-10 IL-16, IL-17A, and IL-18 in severely and critically ill COVID-19 patients, which may persist even after apparent recovery from infection. Biomarker studies on CSF and plasma and serum from COVID-19 patients have also shown a high level of IL-6, intrathecal IgG, neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and tau protein. Emerging evidence on the matter has established the concept of COVID-19 associated neuroinflammation, in the context of COVID-19 associated cytokine storm. While the short-term implications of this condition are extensively documented, its long-term implications are yet to be understood. The association of the aforementioned cytokines with the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington disease, and amyotrophic lateral sclerosis, may increase COVID-19 patients' risk to develop neurodegenerative diseases. Analysis of proinflammatory cytokines and CSF biomarkers in patients with COVID-19 can contribute to the early detection of the disease's exacerbation, monitoring the neurological implications of the disease and devising risk scales, and identifying treatment targets.
Fulltext Case Series of Genetically Confirmed Index Cases of Familial Hypercholesterolemia in Primary Care

Kamal A, Kanchau JD, Shahuri NS, Mohamed-Yassin MS, Baharudin N, Abdul Razak S, et al.

Am J Case Rep, 2023 Apr 27;24:e939489.
PMID: 37185657 DOI: 10.12659/AJCR.939489

BACKGROUND In Malaysia, the prevalence of genetically confirmed heterozygous familial hypercholesterolemia (FH) was reported as 1 in 427. Despite this, FH remains largely underdiagnosed and undertreated in primary care. CASE REPORT In this case series, we report 3 FH cases detected in primary care due to mutations in the low-density lipoprotein receptor (LDLR), apolipoprotein-B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. The mutations in case 1 (frameshift c.660del pathogenic variant in LDLR gene) and case 2 (missense c.10579C>T pathogenic variant in APOB gene) were confirmed as pathogenic, while the mutation in case 3 (missense c.277C>T mutation in PCSK9 gene) may have been benign. In case 1, the patient had the highest LDL-c level, 8.6 mmol/L, and prominent tendon xanthomas. In case 2, the patient had an LDL-c level of 5.7 mmol/L and premature corneal arcus. In case 3, the patient had an LDL-c level of 5.4 mmol/L but had neither of the classical physical findings. Genetic counseling and diagnosis were delivered by primary care physicians. These index cases were initially managed in primary care with statins and therapeutic lifestyle modifications. They were referred to the lipid specialists for up-titration of lipid lowering medications. First-degree relatives were identified and referred for cascade testing. CONCLUSIONS This case series highlights different phenotypical expressions in patients with 3 different FH genetic mutations. Primary care physicians should play a pivotal role in the detection of FH index cases, genetic testing, management, and cascade screening of family members, in partnership with lipid specialists.
Fulltext Stigma, Sociodemographic Factors, and Clinical Factors Associated with Psychological Distress among COVID-19 Survivors during the Convalescence Period: A Multi-Centre Study in Malaysia

Abdul Taib NI, Nik Jaafar NR, Azman N, Leong Bin Abdullah MFI, Mohamad Kamal NA, Baharudin A, et al.

Int J Environ Res Public Health, 2023 Feb 21;20(5).
PMID: 36900807 DOI: 10.3390/ijerph20053795

High rates of psychological distress among COVID-19 survivors and stigmatisation have been reported in both early and late convalescence. This study aimed to compare the severity of psychological distress and to determine the associations among sociodemographic and clinical characteristics, stigma, and psychological distress among COVID-19 survivors across two different cohorts at two different time points. Data were collected cross-sectionally in two groups at one month and six months post-hospitalisation among COVID-19 patient from three hospitals in Malaysia. This study assessed psychological distress and the level of stigma using the Kessler Screening Scale for Psychological Distress (K6) and the Explanatory Model Interview Catalogue (EMIC) stigma scale, respectively. At one month after discharge, significantly lower psychological distress was found among retirees (B = -2.207, 95% confidence interval [95% CI] = -4.139 to -0.068, p = 0.034), those who received up to primary education (B = -2.474, 95% CI = -4.500 to -0.521, p = 0.014), and those who had an income of more than RM 10,000 per month (B = -1.576, 95% CI = -2.714 to -0.505, p = 0.006). Moreover, those with a history of psychiatric illness [one month: (B = 6.363, 95% CI = 2.599 to 9.676, p = 0.002), six months: (B = 2.887, CI = 0.469-6.437, p = 0.038)] and sought counselling services [one month: (B = 1.737, 95% CI = 0.385 to 3.117, p = 0.016), six months: (B = 1.480, CI = 0.173-2.618, p = 0.032)] had a significantly higher severity of psychological distress at one month and six months after discharge from the hospital. The perceived stigma of being infected with COVID-19 contributed to greater severity of psychological distress. (B = 0.197, CI = 0.089-0.300, p = 0.002). Different factors may affect psychological distress at different periods of convalescence after a COVID-19 infection. A persistent stigma contributed to psychological distress later in the convalescence period.
Fulltext A Comprehensive Review on the Processing of Dried Fish and the Associated Chemical and Nutritional Changes

Fitri N, Chan SXY, Che Lah NH, Jam FA, Misnan NM, Kamal N, et al.

Foods, 2022 Sep 20;11(19).
PMID: 36230013 DOI: 10.3390/foods11192938

Fish is a good source of nutrients, although it is easily spoiled. As such, drying is a common method of preserving fish to compensate for its perishability. Dried fish exists in different cultures with varying types of fish used and drying methods. These delicacies are not only consumed for their convenience and for their health benefits, as discussed in this review. Most commonly, salt and spices are added to dried fish to enhance the flavours and to decrease the water activity (aw) of the fish, which further aids the drying process. For fish to be dried effectively, the temperature, drying environment, and time need to be considered along with the butchering method used on the raw fish prior to drying. Considering the various contributing factors, several physicochemical and biochemical changes will certainly occur in the fish. In this review, the pH, water activity (aw), lipid oxidation, and colour changes in fish drying are discussed as well as the proximate composition of dried fish. With these characteristic changes in dried fish, the sensory, microbial and safety aspects of dried fish are also affected, revolving around the preferences of consumers and their health concerns, especially based on how drying is efficient in eliminating/reducing harmful microbes from the fish. Interestingly, several studies have focused on upscaling the efficiency of dried fish production to generate a safer line of dried fish products with less effort and time. An exploratory approach of the published literature was conducted to achieve the purpose of this review. This evaluation gathers important information from all available library databases from 1990 to 2022. In general, this review will benefit the fishery and food industry by enabling them to enhance the efficiency and safety of fish drying, hence minimising food waste without compromising the quality and nutritional values of dried fish.
Cannabidiol and neurodegeneration: From molecular mechanisms to clinical benefits

Jha SK, Nelson VK, Suryadevara PR, Panda SP, Pullaiah CP, Nuli MV, et al.

Ageing Res Rev, 2024 Sep;100:102386.
PMID: 38969143 DOI: 10.1016/j.arr.2024.102386

Neurodegenerative disorders (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis are severe and life-threatening conditions in which significant damage of functional neurons occurs to produce psycho-motor malfunctions. NDs are an important cause of death in the elderly population worldwide. These disorders are commonly associated with the progression of age, oxidative stress, and environmental pollutants, which are the major etiological factors. Abnormal aggregation of specific proteins such as α-synuclein, amyloid-β, huntingtin, and tau, and accumulation of the associated oligomers in neurons are the hallmark pathological features of NDs. Existing therapeutic options for NDs are only symptomatic relief and do not address root-causing factors, such as protein aggregation, oxidative stress, and neuroinflammation. Cannabidiol (CBD) is a non-psychotic natural cannabinoid obtained from Cannabis sativa that possesses multiple pharmacological actions, including antioxidant, anti-inflammatory, and neuroprotective effects in various NDs and other neurological disorders both in vitro and in vivo. CBD has gained attention as a promising drug candidate for the management of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, by inhibiting protein aggregation, free radicals, and neuroinflammation. In parallel, CBD has shown positive results in other neurological disorders, such as epilepsy, depression, schizophrenia, and anxiety, as well as adjuvant treatment with existing standard therapeutic agents. Hence, the present review focuses on exploring the possible molecular mechanisms in controlling various neurological disorders as well as the clinical applications of CBD in NDs including epilepsy, depression and anxiety. In this way, the current review will serve as a standalone reference for the researchers working in this area.
Fulltext A 6-Month Open-Label Study of Vortioxetine among Cancer Patients with Major Depressive Disorder (MDD)

Ng CG, Abousheishaa AA, Low SY, Zainal NZ, Thong KS, Awaluddin AB, et al.

Asian Pac J Cancer Prev, 2023 Aug 01;24(8):2583-2591.
PMID: 37642043 DOI: 10.31557/APJCP.2023.24.8.2583

OBJECTIVE: Vortioxetine is a monoaminergic drug with a novel multimodal mechanism of action. We investigated its efficacy on depressive symptoms, cognitive function, and quality of life among cancer patients.
METHODS: In this multicenter, open-label, single-arm, observational study, patients received flexible doses of Vortioxetine for a period of six months. All participants were assessed at baseline and scheduled for monitoring at weeks 2, 4, 8, 12, 16, 20, and 24. Depression severity was assessed using Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI) scale. The Perceived Deficiency Questionnaire (PDQ-5) assessed the perceived cognitive difficulties in concentration, executive functioning, and memory. The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC) was used to assess the patients' quality of life. Side effects of vortioxetine were monitored using the Antidepressant Side-Effect Checklist (ASEC).
RESULTS: Patients experienced a reduction in MADRS scores from 29.89 ± 5.997 at baseline to 11.59 ± 4.629 by Week 24. The PDQ-5 scores showed significant change from Week-4, whereas the EORTC role, emotional, and cognitive functioning scores showed a significant change from Week 2 onwards. CGI-Severity scores decreased from a baseline of 4.39 ± 0.746 to 2.41 ± 1.085 by Week 24. During the 24-Weeks of therapy, around three-quarters of the patients (73.3%) had one or more adverse events reported on the ASEC. The most frequently reported TEAEs were dry mouth, insomnia, somnolence, and headache, with more than a 30% incidence rate.
CONCLUSION: Vortioxetine seems promising in the management of depression and enhancement of cognitive function and quality of life of cancer patients with Major Depressive Disorder.
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Multicenter outcome analysis of different sheath sizes for Flexible and Navigable Suction ureteral access sheath (FANS) ureteroscopy: an EAU Endourology collaboration with the global FANS study group

Kwok JL, Somani B, Sarica K, Yuen SKK, Zawadzki M, Castellani D, et al.

Urolithiasis, 2024 Nov 15;52(1):162.
PMID: 39545972 DOI: 10.1007/s00240-024-01662-4

Flexible and navigable suction ureteral access sheath (FANS) is a potential game changer in flexible ureteroscopy (FURS). The influence of sheath size on outcomes needs research. The primary aim was to analyze 30-day single stage stone free status (SFS), zero fragment rate (ZFR) and complications when using 10/12Fr sheaths vis a vis other sheath sizes. The global FANS research group published the 30-day outcomes in patients who underwent FANS and reasoned this can be a potential game changer. We included 295 patients from this anonymized dataset with division into two groups: Group 1 (Smaller sheath) - 10/12Fr FANS, and Group 2 (Larger sheath) - 11/13Fr or 12/14Fr sheaths. Stone volume was similar between both groups (median 1320 mm3, p = 0.88). Ureteroscopy and total operative time was longer in the smaller sheath group (35 vs. 32 min, p = 0.02 and 50 vs. 45 min, p = 0.001, respectively). While 30-day computed tomography SFS (100% stone free or single residual fragment ≤ 2 mm) were not significantly different (96% vs. 95%, p > 0.99), ZFR (100% stone-free) was better with smaller sheaths (68% vs. 53%, p = 0.02). There was no difference in postoperative complication rates, and no sepsis in both groups. Urologists should consider individualizing appropriate sheath size in normal adult kidneys. Sheath size did not affect complication rates, risk of perioperative injury to the pelvicalyceal system or ureteric injury, but smaller FANS sheaths had similar high SFS. The ZFR with smaller sheaths was better, but this needs to be validated. These smaller sheath outcomes need to be balanced with longer ureteroscopy time, operative time, reach to the lower pole, ease of suction and visibility during lithotripsy. Large volume studies in different types of pelvicalyceal anatomy can determine if indeed smaller FANS is the best choice in FURS.
A Global Survey to Assess Urologists' Attitudes Towards Suction Technology in Endourology by the European Association of Urology Section of Urolithiasis (EULIS) and Progressive Endourological Association for Research and Leading Solutions (PEARLS)

Gauhar V, Somani BK, Seitz C, Castellani D, Tefik T, Persaud S, et al.

Urology, 2024 Dec 12.
PMID: 39674378 DOI: 10.1016/j.urology.2024.12.009

OBJECTIVE: To assess urologists' perceptions and current practices of using suction-based techniques and technologies in percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS) for kidney stones.
MATERIALS AND METHODS: A customized web-based 28 items questionnaire was created. All participation was voluntary. The survey was hosted on Google Forms between 15th November 2023 and 25th November 2023. Descriptive statistics were applied to demographic details and categorical responses.
RESULTS: 632 responses were received. 56.5% were from Asia. 41.6% of respondents underwent an endourology fellowship. Personal experience of suction for PCNL was noted in 55.4% and 42.7% for RIRS. 34.9% believe that currently there is enough evidence that suction can improve stone free rates and lower complications for both endourology surgeries. 55.69% believe that as evidence evolves, suction has the potential to be a game changer in endourology management of urolithiasis. 55.7% believe that the leading barrier to the adoption of suction in endourology is the lack of availability of technology. Other barriers include lack of procedural standardization (37.65%), lack of evidence (34.9%), lack of proper training (29.58%) and lack of advocation in the current guidelines (17.72%).
CONCLUSION: Our survey shows that urologists are keen to adopt suction for PCNL and RIRS but the lack of definitive evidence, standardization, equipment availability and training preclude them from using so. More high-level evidence regarding the utility of suction in endourology is required for its routine adoption in clinical practice.
Fulltext Assessment of chronic rhinosinusitis with nasal polyps: Development of the Nasal Polyp Patient Assessment Scoring Sheet tool

Alsaleh S, Kamal N, Hopkins C, Al Rand H, Marglani OA, Alterki A, et al.

Laryngoscope Investig Otolaryngol, 2024 Jun;9(3):e1277.
PMID: 38803462 DOI: 10.1002/lio2.1277

BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous disorder with a wide range of validated subjective and objective assessment tools to assess disease severity. However, a comprehensive and easy-to-use tool that integrates these measures for determining disease severity and response to treatment is still obscure. The objective of this study was to develop a standardized assessment tool that facilitates diagnosis, uniform patient monitoring, and comparison of treatment outcomes between different centers both in routine clinical practice and in research.
METHODS: To develop this tool, published literature on assessment tools was searched on various databases. A panel of 12 steering committee members conducted an advisory board meeting to review the findings. Specific outcome measures to be included in a comprehensive assessment tool and follow-up sheet were then collated following consensus approval from the panel. The tool was further validated for content and revised with expert recommendations to arrive at the finalized Nasal Polyp Patient Assessment Scoring Sheet (N-PASS) tool.
RESULTS: The N-PASS tool was developed by integrating the subjective and objective measures for CRS assessment. Based on expert opinions, N-PASS was revised to be used as an easy-to-use guidance tool that captures patient-reported and physician-assessed components for comprehensively assessing disease status and response to treatment.
CONCLUSION: The N-PASS tool can be used to aid in the diagnosis and management of CRS cases with nasal polyps. The tool would also aid in improved monitoring of patients and pave the way for an international disease registry.
LEVEL OF EVIDENCE: Oxford Level 3.
Evaluation of antioxidant, total phenol and flavonoid content and antimicrobial activities of Artocarpus altilis (breadfruit) of underutilized tropical fruit extracts

Jalal TK, Ahmed IA, Mikail M, Momand L, Draman S, Isa ML, et al.

Appl Biochem Biotechnol, 2015 Apr;175(7):3231-43.
PMID: 25649443 DOI: 10.1007/s12010-015-1499-0

Artocarpus altilis (breadfruit) pulp, peel and whole fruit were extracted with various solvents such as hexane, dichloromethane (DCM) and methanol. The antioxidant activity of these extracts were examined using the stable 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging test. IC50 was 55 ± 5.89 μg/ml for the pulp part of methanol extract. In the β-carotene bleaching assay, the antioxidant activity was 90.02 ± 1.51 % for the positive control (Trolox) and 88.34 ± 1.31 % for the pulp part of the fruit methanol extract. The total phenolic content of the crude extracts was determined using the Folin-Ciocalteu procedure; methanol pulp part demonstrated the highest phenol content value of 781 ± 52.97 mg GAE/g of dry sample. While the total flavonoid content was determined using the aluminium chloride colorimetric assay, the highest value of 6213.33 ± 142.22 mg QE/g was indicated by pulp part of the fruit methanol extract. The antimicrobial activity of the crude extracts was tested using disc diffusion method against pathogenic microorganisms: Staphylococcus aureus, Staphylococcus epidermidis, Bacillus cereus, Salmonella typhimurium, Escherichia coli, Klebsiella pneumonia and Candida albicans. Methanol extract of pulp part was recorded to have the highest zone of inhibition against Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration (MIC) and MBC/minimal fungicidal concentration (MFC) for the extracts were also determined using the microdilution method ranging from 4000 to 63 μg/ml against pathogenic microbes. The MBC/MFC values varied from 250 to 4000 μg/ml. A correlation between antioxidant activity assays, antimicrobial activity and phenolic content was established. The results shows that the various parts of A. altilis fruit extracts promising antioxidant activities have potential bioactivities due to high content of phenolic compounds.
Fulltext Synthesis and sar study of diarylpentanoid analogues as new anti-inflammatory agents

Leong SW, Faudzi SM, Abas F, Aluwi MF, Rullah K, Wai LK, et al.

Molecules, 2014 Oct 09;19(10):16058-81.
PMID: 25302700 DOI: 10.3390/molecules191016058

A series of ninety-seven diarylpentanoid derivatives were synthesized and evaluated for their anti-inflammatory activity through NO suppression assay using interferone gamma (IFN-γ)/lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Twelve compounds (9, 25, 28, 43, 63, 64, 81, 83, 84, 86, 88 and 97) exhibited greater or similar NO inhibitory activity in comparison with curcumin (14.7 ± 0.2 µM), notably compounds 88 and 97, which demonstrated the most significant NO suppression activity with IC50 values of 4.9 ± 0.3 µM and 9.6 ± 0.5 µM, respectively. A structure-activity relationship (SAR) study revealed that the presence of a hydroxyl group in both aromatic rings is critical for bioactivity of these molecules. With the exception of the polyphenolic derivatives, low electron density in ring-A and high electron density in ring-B are important for enhancing NO inhibition. Meanwhile, pharmacophore mapping showed that hydroxyl substituents at both meta- and para-positions of ring-B could be the marker for highly active diarylpentanoid derivatives.
Fulltext Anti-tumor activity of Eurycoma longifolia root extracts against K-562 cell line: in vitro and in vivo study

Al-Salahi OS, Ji D, Majid AM, Kit-Lam C, Abdullah WZ, Zaki A, et al.

PLoS One, 2014;9(1):e83818.
PMID: 24409284 DOI: 10.1371/journal.pone.0083818

Eurycoma longifolia Jack has been widely used in traditional medicine for its antimalarial, aphrodisiac, anti-diabetic, antimicrobial and anti-pyretic activities. Its anticancer activity has also been recently reported on different solid tumors, however no anti-leukemic activity of this plant has been reported. Thus the present study assesses the in vitro and in vivo anti-proliferative and apoptotic potentials of E. longifolia on K-562 leukemic cell line. The K-562 cells (purchased from ATCC) were isolated from patients with chronic myelocytic leukemia (CML) were treated with the various fractions (TAF273, F3 and F4) of E. longifolia root methanolic extract at various concentrations and time intervals and the anti-proliferative activity assessed by MTS assay. Flow cytometry was used to assess the apoptosis and cell cycle arrest. Nude mice injected subcutaneously with 10(7) K-562 cells were used to study the anti-leukemic activity of TAF273 in vivo. TAF273, F3 and F4 showed various degrees of growth inhibition with IC50 values of 19, 55 and 62 µg/ml, respectively. TAF273 induced apoptosis in a dose and time dependent manner. TAF273 arrested cell cycle at G1 and S phases. Intraperitoneal administration of TAF273 (50 mg/kg) resulted in a significant growth inhibition of subcutaneous tumor in TAF273-treated mice compared with the control mice (P = 0.024). TAF273 shows potent anti-proliferative activity in vitro and in vivo models of CML and therefore, justifies further efforts to define more clearly the potential benefits of using TAF273 as a novel therapeutic strategy for CML management.
Fulltext Global transcriptional analysis of Burkholderia pseudomallei high and low biofilm producers reveals insights into biofilm production and virulence

Chin CY, Hara Y, Ghazali AK, Yap SJ, Kong C, Wong YC, et al.

BMC Genomics, 2015;16:471.
PMID: 26092034 DOI: 10.1186/s12864-015-1692-0

Chronic bacterial infections occur as a result of the infecting pathogen's ability to live within a biofilm, hence escaping the detrimental effects of antibiotics and the immune defense system. Burkholderia pseudomallei, a gram-negative facultative pathogen, is distinctive in its ability to survive within phagocytic and non-phagocytic cells, to persist in vivo for many years and subsequently leading to relapse as well as the development of chronic disease. The capacity to persist has been attributed to the pathogen's ability to form biofilm. However, the underlying biology of B. pseudomallei biofilm development remains unresolved.
Identification of biomarkers and genetic approaches toward chronic obstructive pulmonary disease

Wadhwa R, Aggarwal T, Malyla V, Kumar N, Gupta G, Chellappan DK, et al.

J Cell Physiol, 2019 08;234(10):16703-16723.
PMID: 30912142 DOI: 10.1002/jcp.28482

Chronic obstructive pulmonary disease accounts as the leading cause of mortality worldwide prominently affected by genetic and environmental factors. The disease is characterized by persistent coughing, breathlessness airways inflammation followed by a decrease in forced expiratory volume1 and exacerbations, which affect the quality of life. Determination of genetic, epigenetic, and oxidant biomarkers to evaluate the progression of disease has proved complicated and challenging. Approaches including exome sequencing, genome-wide association studies, linkage studies, and inheritance and segregation studies played a crucial role in the identification of genes, their pathways and variation in genes. This review highlights multiple approaches for biomarker and gene identification, which can be used for differential diagnosis along with the genome editing tools to study genes associated with the development of disease and models their function. Further, we have discussed the approaches to rectify the abnormal gene functioning of respiratory tissues and various novel gene editing techniques like Zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN), and clustered regulatory interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9).
Fulltext Novel triple‑positive markers identified in human non‑small cell lung cancer cell line with chemotherapy-resistant and putative cancer stem cell characteristics

Satar NA, Fakiruddin KS, Lim MN, Mok PL, Zakaria N, Fakharuzi NA, et al.

Oncol Rep, 2018 Aug;40(2):669-681.
PMID: 29845263 DOI: 10.3892/or.2018.6461

Through the specific identification and direct targeting of cancer stem cells (CSCs), it is believed that a better treatment efficacy of cancer may be achieved. Hence, the present study aimed to identify a CSC subpopulation from adenocarcinoma cells (A549) as a model of non‑small cell lung cancer (NSCLC). Ιnitially, we sorted two subpopulations known as the triple‑positive (EpCAM+/CD166+/CD44+) and triple‑negative (EpCAM-/CD166-/CD44-) subpopulation using fluorescence-activated cell sorting (FACS). Sorted cells were subsequently evaluated for proliferation and chemotherapy-resistance using a viability assay and were further characterized for their clonal heterogeneity, self-renewal characteristics, cellular migration, alkaline dehydrogenase (ALDH) activity and the expression of stemness-related genes. According to our findings the triple‑positive subpopulation revealed significantly higher (P<0.01) proliferation activity, exhibited better clonogenicity, was mostly comprised of holoclones and had markedly bigger (P<0.001) spheroid formation indicating a better self-renewal capacity. A relatively higher resistance to both 5‑fluouracil and cisplatin with 80% expression of ALDH was observed in the triple‑positive subpopulation, compared to only 67% detected in the triple‑negative subpopulation indicated that high ALDH activity contributed to greater chemotherapy-resistance characteristics. Higher percentage of migrated cells was observed in the triple‑positive subpopulation with 56% cellular migration being detected, compared to only 19% in the triple‑negative subpopulation on day 2. This was similarly observed on day 3 in the triple‑positive subpopulation with 36% higher cellular migration compared to the triple‑negative subpopulation. Consistently, elevated levels of the stem cell genes such as REX1 and SSEA4 were also found in the triple‑positive subpopulation indicating that the subpopulation displayed a strong characteristic of pluripotency. In conclusion, our study revealed that the triple‑positive subpopulation demonstrated similar characteristics to CSCs compared to the triple‑negative subpopulation. It also confirmed the feasibility of using the triple‑positive (EpCAM+/CD166+/CD44+) marker as a novel candidate marker that may lead to the development of novel therapies targeting CSCs of NSCLC.
Late Relapse of Diabetes After Bariatric Surgery: Not Rare, but Not a Failure

Aminian A, Vidal J, Salminen P, Still CD, Nor Hanipah Z, Sharma G, et al.

Diabetes Care, 2020 03;43(3):534-540.
PMID: 31974105 DOI: 10.2337/dc19-1057

OBJECTIVE: To characterize the status of cardiometabolic risk factors after late relapse of type 2 diabetes mellitus (T2DM) and to identify factors predicting relapse after initial diabetes remission following bariatric surgery to construct prediction models for clinical practice.
RESEARCH DESIGN AND METHODS: Outcomes of 736 patients with T2DM who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at an academic center (2004-2012) and had ≥5 years' glycemic follow-up were assessed. Of 736 patients, 425 (58%) experienced diabetes remission (HbA1c <6.5% [48 mmol/mol] with patients off medications) in the 1st year after surgery. These 425 patients were followed for a median of 8 years (range 5-14) to characterize late relapse of diabetes.
RESULTS: In 136 (32%) patients who experienced late relapse, a statistically significant improvement in glycemic control, number of diabetes medications including insulin use, blood pressure, and lipid profile was still observed at long-term. Independent baseline predictors of late relapse were preoperative number of diabetes medications, duration of T2DM before surgery, and SG versus RYGB. Furthermore, patients who relapsed lost less weight during the 1st year after surgery and regained more weight afterward. Prediction models were constructed and externally validated.
CONCLUSIONS: While late relapse of T2DM is a real phenomenon (one-third of our cohort), it should not be considered a failure, as the trajectory of the disease and its related cardiometabolic risk factors is changed favorably after bariatric surgery. Earlier surgical intervention, RYGB (compared with SG) and more weight loss (less late weight regain) are associated with less diabetes relapse in the long-term.
Immunological axis of curcumin-loaded vesicular drug delivery systems

Chellappan DK, Ng ZY, Wong JY, Hsu A, Wark P, Hansbro N, et al.

Future Med Chem, 2018 04 01;10(8):839-844.
PMID: 29620416 DOI: 10.4155/fmc-2017-0245

Several vesicular systems loaded with curcumin have found their way in the therapeutic applications of several diseases, primarily acting through their immunological pathways. Such systems use particles at a nanoscale range, bringing about their intended use through a range of complex mechanisms. Apart from delivering drug substances into target tissues, these vesicular systems also effectively overcome problems like insolubility and unequal drug distribution. Several mechanisms are explored lately by different workers, and interest over vesicular curcumin has been renewed in the past decade. This commentary discusses several immunological targets in which curcumin is employed in a vesicular form.
Combinational effect of angiotensin receptor blocker and folic acid therapy on uric acid and creatinine level in hyperhomocysteinemia-associated hypertension

Singh Y, Samuel VP, Dahiya S, Gupta G, Gillhotra R, Mishra A, et al.

Biotechnol Appl Biochem, 2019 Sep;66(5):715-719.
PMID: 31314127 DOI: 10.1002/bab.1799

Homocysteine [HSCH2 CH2 CH(NH2 )COOH] (Hcy) is a sulfur-containing amino acid of 135.18 Da of molecular weight, generated during conversion of methionine to cysteine. If there is a higher accumulation of Hcy in the blood, that is usually above 15 µmol/L, it leads to a condition referred to as hyperhomocysteinemia. A meta-analysis of observational study suggested an elevated concentration of Hcy in blood, which is termed as the risk factors leading to ischemic heart disease and stroke. Further experimental studies stated that Hcy can lead to an increase in the proliferation of vascular smooth muscle cells and functional impairment of endothelial cells. The analyses confirmed some of the predictors for Hcy presence, such as serum uric acid (UA), systolic blood pressure, and hematocrit. However, angiotensin-converting enzyme inhibitors angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) alone are inadequate for controlling UA and creatinine level, although the addition of folic acid may be beneficial in hypertensive patients who are known to have a high prevalence of elevated Hcy. We hypothesized that combination therapy with an ARB (olmesartan) and folic acid is a promising treatment for lowering the UA and creatinine level in hyperhomocysteinemia-associated hypertension.
Applications of Nanocarriers as Drug Delivery Vehicles for Active Phytoconstituents

Ng PQ, Ling LSC, Chellian J, Madheswaran T, Panneerselvam J, Kunnath AP, et al.

Curr Pharm Des, 2020;26(36):4580-4590.
PMID: 32520681 DOI: 10.2174/1381612826666200610111013

Many plant-based bioactive compounds have been serving as the origin of drugs since long ago and many of them have been proven to have medicinal value against various chronic diseases, including, cancer, arthritis, hepatic diseases, type-2 diabetes and cardiovascular diseases. However, their clinical applications have been limited due to their poor water solubility, stability, low bioavailability and extensive transformation due to the first-pass metabolism. The applications of nanocarriers have been proven to be able to improve the delivery of bioactive phytoconstituents, resulting in the enhancement of various pharmacokinetic properties and thereby increasing the therapeutic value of phytoconstituents. These biocompatible nanocarriers also exert low toxicity to healthy cells. This review focuses on the uses and applications of different types of nanocarriers to enhance the delivery of phytoconstituents for the treatment of various chronic diseases, along with comparisons related to bioavailability and therapeutic efficacy of nano phytoconstituents with native phytoconstituents.
Fulltext Interferon therapy for preventing COPD exacerbations

Mehta M, Paudel KR, Shukla SD, Shastri MD, Singh SK, Gulati M, et al.

EXCLI J, 2020;19:1477-1480.
PMID: 33312108 DOI: 10.17179/excli2020-2997

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