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Fulltext Transcriptional landscape of Burkholderia pseudomallei cultured under environmental and clinical conditions

Kong C, Wong RR, Ghazali AK, Hara Y, Tengku Aziz TN, Nathan S

Microb Genom, 2023 Apr;9(4).
PMID: 37018040 DOI: 10.1099/mgen.0.000982

Burkholderia pseudomallei, a Gram-negative pathogen, is the causative agent of melioidosis in humans. This bacterium can be isolated from the soil, stagnant and salt-water bodies, and human and animal clinical specimens. While extensive studies have contributed to our understanding of B. pseudomallei pathogenesis, little is known about how a harmless soil bacterium adapts when it shifts to a human host and exhibits its virulence. The bacterium's large genome encodes an array of factors that support the pathogen's ability to survive under stressful conditions, including the host's internal milieu. In this study, we performed comparative transcriptome analysis of B. pseudomallei cultured in human plasma versus soil extract media to provide insights into B. pseudomallei gene expression that governs bacterial adaptation and infectivity in the host. A total of 455 genes were differentially regulated; genes upregulated in B. pseudomallei grown in human plasma are involved in energy metabolism and cellular processes, whilst the downregulated genes mostly include fatty acid and phospholipid metabolism, amino acid biosynthesis and regulatory function proteins. Further analysis identified a significant upregulation of biofilm-related genes in plasma, which was validated using the biofilm-forming assay and scanning electron microscopy. In addition, genes encoding known virulence factors such as capsular polysaccharide and flagella were also overexpressed, suggesting an overall enhancement of B. pseudomallei virulence potential when present in human plasma. This ex vivo gene expression profile provides comprehensive information on B. pseudomallei's adaptation when shifted from the environment to the host. The induction of biofilm formation under host conditions may explain the difficulty in treating septic melioidosis.
High Interest in Long-acting Injectable Pre-exposure Prophylaxis (LAI-PrEP) for HIV Prevention Among Men Who Have Sex With Men (MSM): Result From A Nationwide Survey in Malaysia

Paudel K, Gupta S, Gautam K, Wickersham JA, Khati A, Azwa I, et al.

J Community Health, 2023 Jun;48(3):513-521.
PMID: 36732459 DOI: 10.1007/s10900-023-01195-8

The recent approval of long-acting injectable cabotegravir (CAB-LA) as PrEP for HIV prevention could be an attractive alternative for MSM, particularly among those who face barriers to adherence using the oral pill. This study reports on the awareness of long-acting injectable PrEP (LAI-PrEP) and factors associated with interest in LAI-PrEP use among a nationwide sample of MSM in Malaysia. An online cross-sectional survey was conducted between August and September 2021 to explore perspectives on PrEP modalities among Malaysian MSM (N = 870). Convenience sampling was used to recruit participants using ads on two platforms hornet and facebook. While only 9.1% of the study participants were aware of LAI-PrEP, the majority had heard of oral PrEP (80.9%). After giving a description of it, a large majority (86.6%) expressed interest in using it if made accessible. Those who had a prior history of HIV testing (aOR = 1.9; 95% CI = 1.2-3.2) were more likely to use LAI-PrEP. Interestingly, despite the concerns related to potential high cost (aOR = 3.4; 95% CI = 2.1-5.5) and long-term side effects (aOR = 1.9; 95% CI = 1.2-3.1), the majority of the participants were interested in using LAI-PrEP. Those who were afraid of (or disliked) syringes were less interested in using it (aOR = 0.2; 95% CI; 0.1-0.4). In the recent context that LAI-PrEP was shown to be safe and effective at preventing HIV, our results indicate its potential relevance as an additional PrEP option that could accelerate the uptake and scale-up of PrEP. However, it is crucial to conduct future research urgently to improve the understanding of strategies that could enhance the accessibility, acceptability, and affordability of LAI-PrEP for MSM in low- and middle-income countries, including Malaysia.
Senolytics: Opening avenues in drug discovery to find novel therapeutics for Parkinson's Disease

Kakoty V, Kalarikkal Chandran S, Gulati M, Goh BH, Dua K, Kumar Singh S

Drug Discov Today, 2023 Jun;28(6):103582.
PMID: 37023942 DOI: 10.1016/j.drudis.2023.103582

Aging is one of the major risk factors for most neurodegenerative disorders including Parkinson's disease (PD). More than 10 million people are affected with PD worldwide. One of the predominant factors accountable for progression of PD pathology could be enhanced accumulation of senescent cells in the brain with the progress of age. Recent investigations have highlighted that senescent cells can ignite PD pathology via increased oxidative stress and neuroinflammation. Senolytics are agents that kill senescent cells. This review mainly focuses on understanding the pathological connection between senescence and PD, with emphasis on some of the recent advances made in the area of senolytics and their evolution to potential clinical candidates for future pharmaceuticals against PD.
Fulltext Data on known anti-virals in combating CoVid-19

Akshayaa L, Lakshmi T, Devaraj E, Roy A, Raghunandhakumar S, Sivaperumal P, et al.

Bioinformation, 2020;16(11):878-881.
PMID: 34803262 DOI: 10.6026/97320630016878

Design and development of effective anti-virals in combating CoVid-19 is a great challenge worldwide. Known drugs such as chloroquine, lopinavir, favipiravir and remdesivir are used in the management of CoVid - 19. It is known that Ivermectin and remdesivir both are effective against filoviruses, paramyxo viruses. Available data also shows that ivermectin and remedesivir repress the replication of SARS-CoV-2. Thus, we document the potential use of ivermectin and remdesivir in the management of CoVid -19.
Fulltext Synthesis, spectroscopic, electrochemical and photophysical properties of high band gap polymers for potential applications in semi-transparent solar cells

Amin PO, Ketuly KA, Saeed SR, Muhammadsharif FF, Symes MD, Paul A, et al.

BMC Chem, 2021 Apr 21;15(1):25.
PMID: 33883016 DOI: 10.1186/s13065-021-00751-4

BACKGROUND: The design of new polymers able to filter the electromagnetic spectrum and absorb distinctly in the UV and high-energy part of visible spectrum is crucial for the development of semi-transparent solar cells. Herein, we report on the synthesis and spectroscopic, electrochemical, and photophysical characteristics of three new polymers, namely (i) Poly(triamterene-co-terephthalate), (ii) Poly[triamterene-co- 3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine-p,p'-disulfonamide], and (iii) Poly(5-hydroxyindole-2-carboxylate) that might show promise as materials for semi-transparent solar cells.
RESULTS: The energy band gap, refractive index, dielectric constant, and optical conductivity of the electron donor polymer, poly(triamterene-co-terephthalate), were determined to be 2.92 eV, 1.56, 2.44 and 2.43 × 104 S cm-1, respectively. The synthesized electron acceptor polymers showed a relatively high refractive index, dielectric constant, and optical conductivity. The presence of a direct allowed transition was confirmed between intermolecular energy bands of the polymers.
CONCLUSIONS: The polymers showed relatively high energy gap and deep HOMO levels, making them strong absorbers of photons in the UV region and high energy part of the visible region. The synthesized donor and acceptors performed well relative to P3HT and fullerenes due to the close match of the HOMO and LUMO levels. With further development, the polymers could be viable for use as the active layers of semi-transparent solar cells.
Fulltext Pre-exposure prophylaxis service among men who have sex with men in Malaysia: findings from a discrete choice experiment

Dubov A, Altice FL, Gutierrez JI, Wickersham JA, Azwa I, Kamarulzaman A, et al.

Sci Rep, 2023 Aug 30;13(1):14200.
PMID: 37648731 DOI: 10.1038/s41598-023-41264-5

Men who have sex with men (MSM) in Malaysia are disproportionately affected by HIV. As pre-exposure prophylaxis (PrEP) is being introduced, we assessed population-based PrEP delivery preferences among MSM in Malaysia. We conducted a discrete choice experiment through an online survey among 718 MSM. The survey included 14 choice tasks presenting experimentally varied combinations of five attributes related to PrEP delivery (i.e., cost, dosing strategy, clinician interaction strategy, dispensing venue, and burden of visits to start PrEP). We used latent class analysis and Hierarchical Bayesian modeling to generate the relative importance of each attribute and preference across six possible PrEP delivery programs. PrEP dosing, followed by cost, was the most important attribute. The participants were clustered into five preference groups. Two groups (n = 290) most commonly preferred on-demand, while the other three preferred injectable PrEP. One group (n = 188) almost exclusively considered cost in their decision-making, and the smallest group (n = 86) was substantially less interested in PrEP for reasons unrelated to access. In simulated scenarios, PrEP initiation rates varied by the type of program available to 55·0% of MSM. Successful PrEP uptake among Malaysian MSM requires expanding beyond daily oral PrEP to on-demand and long-acting injectable PrEP, especially at affordable cost.
Gefitinib as first line therapy in Malaysian patients with EGFR mutation-positive non-small-cell lung cancer: A single-center retrospective study

Abdullah MM, Bhat A, Mohamed AK, Ching FY, Ahmed N, Gantotti S

Oncol Lett, 2016 Apr;11(4):2757-2762.
PMID: 27073548

The present retrospective, single-center study evaluated the objective response rate (ORR) and progression-free survival (PFS) of epidermal growth factor receptor (EGFR) mutation-positive Malaysian patients with advanced lung adenocarcinoma treated with gefitinib. During May 2008 to July 2013, 33 patients with Stage IV, EGFR mutation-positive non-small-cell lung cancer (NSCLC) were identified and received gefitinib (250 mg) as first line treatment. The primary and secondary end points were ORR, PFS and safety, respectively. A total of 18 (54.5%) and 2 (6.1%) patients achieved partial response (PR) and complete response (CR) to gefitinib therapy, respectively, yielding an ORR of 60.6% (95% CI, 42.1-77.1%). Patients with exon 20 or 21 mutations (n=6, 66.7%) tended to have better ORR compared with exon 19 (n=22, 59.1%). The median PFS was 8.9 months in Malaysian patients with EGFR mutation-positive NSCLC, treated with gefitinib. The majority of treatment-related toxicity was mild in nature. The most frequently reported adverse events included dry skin (39.4%), skin rash (27.2%), and dermatitis acneiform (15.2%). In conclusion, Malaysian patients with locally advanced and metastatic EGFR mutation-positive NSCLC responded favorably to gefitinib therapy in terms of ORR, median PFS, and tolerability, the results of which were consistent with those of the IPASS study conducted in an Asian population. Considering the efficacy and safety profile of gefitinib, it is a favorable option for the first-line treatment of Malaysian patients with EGFR mutation-positive NSCLC. However, future long-term studies in a larger population of Malaysian patients are required to support whether the prolonged PFS conferred by gefitinib will translate into prolonged overall survival.
Vitamin D, Calbindin, and calcium signaling: Unraveling the Alzheimer's connection

Acharya M, Singh N, Gupta G, Tambuwala MM, Aljabali AAA, Chellappan DK, et al.

Cell Signal, 2024 Apr;116:111043.
PMID: 38211841 DOI: 10.1016/j.cellsig.2024.111043

Calcium is a ubiquitous second messenger that is indispensable in regulating neurotransmission and memory formation. A precise intracellular calcium level is achieved through the concerted action of calcium channels, and calcium exerts its effect by binding to an array of calcium-binding proteins, including calmodulin (CAM), calcium-calmodulin complex-dependent protein kinase-II (CAMK-II), calbindin (CAL), and calcineurin (CAN). Calbindin orchestrates a plethora of signaling events that regulate synaptic transmission and depolarizing signals. Vitamin D, an endogenous fat-soluble metabolite, is synthesized in the skin upon exposure to ultraviolet B radiation. It modulates calcium signaling by increasing the expression of the calcium-sensing receptor (CaSR), stimulating phospholipase C activity, and regulating the expression of calcium channels such as TRPV6. Vitamin D also modulates the activity of calcium-binding proteins, including CAM and calbindin, and increases their expression. Calbindin, a high-affinity calcium-binding protein, is involved in calcium buffering and transport in neurons. It has been shown to inhibit apoptosis and caspase-3 activity stimulated by presenilin 1 and 2 in AD. Whereas CAM, another calcium-binding protein, is implicated in regulating neurotransmitter release and memory formation by phosphorylating CAN, CAMK-II, and other calcium-regulated proteins. CAMK-II and CAN regulate actin-induced spine shape changes, which are further modulated by CAM. Low levels of both calbindin and vitamin D are attributed to the pathology of Alzheimer's disease. Further research on vitamin D via calbindin-CAMK-II signaling may provide newer insights, revealing novel therapeutic targets and strategies for treatment.
Fulltext Towards Multiplex Molecular Diagnosis-A Review of Microfluidic Genomics Technologies

Basha IHK, Ho ETW, Yousuff CM, Hamid NHB

Micromachines (Basel), 2017 Aug 30;8(9).
PMID: 30400456 DOI: 10.3390/mi8090266

Highly sensitive and specific pathogen diagnosis is essential for correct and timely treatment of infectious diseases, especially virulent strains, in people. Point-of-care pathogen diagnosis can be a tremendous help in managing disease outbreaks as well as in routine healthcare settings. Infectious pathogens can be identified with high specificity using molecular methods. A plethora of microfluidic innovations in recent years have now made it increasingly feasible to develop portable, robust, accurate, and sensitive genomic diagnostic devices for deployment at the point of care. However, improving processing time, multiplexed detection, sensitivity and limit of detection, specificity, and ease of deployment in resource-limited settings are ongoing challenges. This review outlines recent techniques in microfluidic genomic diagnosis and devices with a focus on integrating them into a lab on a chip that will lead towards the development of multiplexed point-of-care devices of high sensitivity and specificity.
Fulltext Advanced drug delivery systems can assist in managing influenza virus infection: A hypothesis

Chan Y, Ng SW, Mehta M, Anand K, Kumar Singh S, Gupta G, et al.

Med Hypotheses, 2020 Nov;144:110298.
PMID: 33254489 DOI: 10.1016/j.mehy.2020.110298

Outbreaks of influenza infections in the past have severely impacted global health and socioeconomic growth. Antivirals and vaccines are remarkable medical innovations that have been successful in reducing the rates of morbidity and mortality from this disease. However, the relentless emergence of drug resistance has led to a worrisome increase in the trend of influenza outbreaks, characterized by worsened clinical outcomes as well as increased economic burden. This has prompted the need for breakthrough innovations that can effectively manage influenza outbreaks. This article provides an insight into a novel hypothesis that describes how the integration of nanomedicine, with the development of drugs and vaccines can potentially enhance body immune response and the efficacies of anti-viral therapeutics to combat influenza infections.
Fulltext Targeted delivery of 5-fluorouracil-1-acetic acid (5-FA) to cancer cells overexpressing epithelial growth factor receptor (EGFR) using virus-like nanoparticles

Gan BK, Rullah K, Yong CY, Ho KL, Omar AR, Alitheen NB, et al.

Sci Rep, 2020 Oct 08;10(1):16867.
PMID: 33033330 DOI: 10.1038/s41598-020-73967-4

Chemotherapy is widely used in cancer treatments. However, non-specific distribution of chemotherapeutic agents to healthy tissues and normal cells in the human body always leads to adverse side effects and disappointing therapeutic outcomes. Therefore, the main aim of this study was to develop a targeted drug delivery system based on the hepatitis B virus-like nanoparticle (VLNP) for specific delivery of 5-fluorouracil-1-acetic acid (5-FA) to cancer cells expressing epithelial growth factor receptor (EGFR). 5-FA was synthesized from 5-fluorouracil (5-FU), and it was found to be less toxic than the latter in cancer cells expressing different levels of EGFR. The cytotoxicity of 5-FA increased significantly after being conjugated on the VLNP. A cell penetrating peptide (CPP) of EGFR was displayed on the VLNP via the nanoglue concept, for targeted delivery of 5-FA to A431, HT29 and HeLa cells. The results showed that the VLNP displaying the CPP and harboring 5-FA internalized the cancer cells and killed them in an EGFR-dependent manner. This study demonstrated that the VLNP can be used to deliver chemically modified 5-FU derivatives to cancer cells overexpressing EGFR, expanding the applications of the VLNP in targeted delivery of chemotherapeutic agents to cancer cells overexpressing this transmembrane receptor.
Fulltext Analytical and qualitative investigation of COVID-19 mathematical model under fractional differential operator

Shah K, Sher M, Rabai'ah H, Ahmadian A, Salahshour S, Pansera BA

Math Methods Appl Sci, 2021 Aug 22.
PMID: 34908635 DOI: 10.1002/mma.7704

In the current article, we aim to study in detail a novel coronavirus (2019-nCoV or COVID-19) mathematical model for different aspects under Caputo fractional derivative. First, from analysis point of view, existence is necessary to be investigated for any applied problem. Therefore, we used fixed point theorem's due to Banach's and Schaefer's to establish some sufficient results regarding existence and uniqueness of the solution to the proposed model. On the other hand, stability is important in respect of approximate solution, so we have developed condition sufficient for the stability of Ulam-Hyers and their different types for the considered system. In addition, the model has also been considered for semianalytical solution via Laplace Adomian decomposition method (LADM). On Matlab, by taking some real data about Pakistan, we graph the obtained results. In the last of the manuscript, a detail discussion and brief conclusion are provided.
Fulltext Transitioning from Soil to Host: Comparative Transcriptome Analysis Reveals the Burkholderia pseudomallei Response to Different Niches

Ghazali AK, Firdaus-Raih M, Uthaya Kumar A, Lee WK, Hoh CC, Nathan S

Microbiol Spectr, 2023 Mar 01;11(2):e0383522.
PMID: 36856434 DOI: 10.1128/spectrum.03835-22

Burkholderia pseudomallei, a soil and water saprophyte, is responsible for the tropical human disease melioidosis. A hundred years since its discovery, there is still much to learn about B. pseudomallei proteins that are essential for the bacterium's survival in and interaction with the infected host, as well as their roles within the bacterium's natural soil habitat. To address this gap, bacteria grown under conditions mimicking the soil environment were subjected to transcriptome sequencing (RNA-seq) analysis. A dual RNA-seq approach was used on total RNA from spleens isolated from a B. pseudomallei mouse infection model at 5 days postinfection. Under these conditions, a total of 1,434 bacterial genes were induced, with 959 induced in the soil environment and 475 induced in bacteria residing within the host. Genes encoding metabolism and transporter proteins were induced when the bacteria were present in soil, while virulence factors, metabolism, and bacterial defense mechanisms were upregulated during active infection of mice. On the other hand, capsular polysaccharide and quorum-sensing pathways were inhibited during infection. In addition to virulence factors, reactive oxygen species, heat shock proteins, siderophores, and secondary metabolites were also induced to assist bacterial adaptation and survival in the host. Overall, this study provides crucial insights into the transcriptome-level adaptations which facilitate infection by soil-dwelling B. pseudomallei. Targeting novel therapeutics toward B. pseudomallei proteins required for adaptation provides an alternative treatment strategy given its intrinsic antimicrobial resistance and the absence of a vaccine. IMPORTANCE Burkholderia pseudomallei, a soil-dwelling bacterium, is the causative agent of melioidosis, a fatal infectious disease of humans and animals. The bacterium has a large genome consisting of two chromosomes carrying genes that encode proteins with important roles for survival in diverse environments as well as in the infected host. While a general mechanism of pathogenesis has been proposed, it is not clear which proteins have major roles when the bacteria are in the soil and whether the same proteins are key to successful infection and spread. To address this question, we grew the bacteria in soil medium and then in infected mice. At 5 days postinfection, bacteria were recovered from infected mouse organs and their gene expression was compared against that of bacteria grown in soil medium. The analysis revealed a list of genes expressed under soil growth conditions and a different set of genes encoding proteins which may be important for survival, replication, and dissemination in an infected host. These proteins are a potential resource for understanding the full adaptation mechanism of this pathogen. In the absence of a vaccine for melioidosis and with treatment being reliant on combinatorial antibiotic therapy, these proteins may be ideal targets for designing antimicrobials to treat melioidosis.
Carbohydrate mouth rinse is no more effective than placebo on running endurance of dehydrated and heat acclimated athletes

Kamaruddin HK, Farah NMF, Aziz AR, Mündel T, Che Muhamed AM

Eur J Appl Physiol, 2023 Jul;123(7):1507-1518.
PMID: 36920510 DOI: 10.1007/s00421-023-05170-y

PURPOSE: To determine whether carbohydrate mouth rinsing would improve endurance running performance of tropical natives in a warm-humid (30 °C and 70% relative humidity) environment.
METHOD: Twelve endurance male runners [age 25 ± 3 years; peak aerobic capacity ([Formula: see text]O2peak) 57.6 ± 3.6 mL.kg-1.min-1] completed three time-to-exhaustion (TTE) trials at ~ 70% [Formula: see text]O2peak while swilling 25 ml of a 6% carbohydrate (CHO) or taste-matched placebo (PLA) as well as no mouth rinse performed in the control (CON) trial.
RESULTS: TTE performance was significantly longer in both CHO and PLA trials when compared with the CON trial (54.7 ± 5.4 and 53.6 ± 5.1 vs. 48.4 ± 3.6 min, respectively; p 0.05). Similarly, plasma lactate and glucose as well as exercise heart rate were not influenced by the trials.
CONCLUSIONS: The present study demonstrates that mouth rinsing, whether carbohydrate or placebo, provides an ergogenic benefit to running endurance when compared to CON in a heat stress environment. Nevertheless, the results do not support the notion that rinsing a carbohydrate solution provides a greater advantage as previously described among non-heat acclimated individuals within a temperate condition.
Fabrication of chitosan@activated carbon composites in EmimAc for Cd(II) adsorption from aqueous solution: Experimental, optimization and DFT study

Saheed IO, Yusof ENM, Oh WD, Hanafiah MAKM, Suah FBM

Int J Biol Macromol, 2023 Jul 01;242(Pt 2):124798.
PMID: 37178882 DOI: 10.1016/j.ijbiomac.2023.124798

Adsorption efficiency of a duo-material blend featuring the fabrication of modified chitosan adsorbents (powder (C-emimAc), bead (CB-emimAc) and sponge (CS-emimAc)) for the removal of Cd(II) from aqueous solution was investigated. The chitosan@activated carbon (Ch/AC) blend was developed in a green ionic solvent, 1-ethyl-3-methyl imidazolium acetate (EmimAc) and its characteristics was examined using FTIR, SEM, EDX, BET and TGA. The possible mechanism of interaction between the composites and Cd(II) was also predicted using the density functional theory (DFT) analysis. The interactions of various blend forms (C-emimAc, CB-emimAc and CS-emimAc) with Cd(II) gave better adsorption at pH 6. The composites also present excellent chemical stability in both acidic and basic conditions. The monolayer adsorption capacities obtained (under the condition 20 mg/L [Cd], adsorbent dosage 5 mg, contact time 1 h) for the CB-emimAc (84.75 mg/g) > C-emimAc (72.99 mg/g) > CS-emimAc (55.25 mg/g), as this was supported by their order of increasing BET surface area (CB-emimAc (120.1 m2/g) > C-emimAc (67.4 m2/g) > CS-emimAc (35.3 m2/g)). The feasible adsorption interactions between Cd(II) and Ch/AC occurs through the O-H and N-H groups of the composites, as supported by DFT analysis in which an electrostatic interactions was predicted as the dominant force. The interaction energy (-1309.35 eV) calculated via DFT shows that the Ch/AC with amino (-NH) and hydroxyl (-OH) groups are more effective with four significant electrostatic interactions with the Cd(II) ion. The various form of Ch/AC composites developed in EmimAc possess good adsorption capacity and stability for the adsorption Cd(II).
APPLICATION OF FUZZY DELPHI METHOD TO VALIDATE CONTENT OF SPIRITUAL INTELLIGENCE INSTRUMENT FOR MUSLIM NURSES

Atarhim MA, Manap J, Mastor KA, Mokhtar MK, Yusof A, Zabidi AFM

J Nurs Meas, 2023 Jun 01;31(2):202-218.
PMID: 37277156 DOI: 10.1891/JNM-2021-0012

Background & Purpose: This study aims to consolidate expert views and validated 371 items for developing spiritual intelligence instrument for Muslim nurses guided by the Spiritual Intelligence Model for Human Excellence (SIMHE). Methods: A Fuzzy Delphi Method (FDM) was used to validate these items and analyzed with Triangular Fuzzy Numbers and Defuzzification process. Views from 20 experts from three different backgrounds, namely, theology/Sufism, psychology and Islamic counseling, and evaluation and measurement, were also included in the validation process. Results: All items fulfilled the prerequisite of a threshold level of (d) ≤ 0.2, which obtained more than 75% of expert consensus and α-cut value ≥ of 0.5. Conclusion: The FDM analysis results indicated that all items could further validate the instrument using Rasch measurement analysis.
Systematic review and meta-analysis of mesenchymal stromal/stem cells as strategical means for the treatment of COVID-19

Taufiq H, Shaik Fakiruddin K, Muzaffar U, Lim MN, Rusli S, Kamaluddin NR, et al.

Ther Adv Respir Dis, 2023;17:17534666231158276.
PMID: 37128999 DOI: 10.1177/17534666231158276

BACKGROUND: In coronavirus disease 2019 (COVID-19) patients, elevated levels of inflammatory cytokines from over stimulation of immune cells have become a concern due to the potential outburst of cytokine storm that damages the tissues and organs, especially the lungs. This leads to the manifestation of COVID-19 symptoms, such as pneumonia, acute respiratory distress syndrome (ARDS), multiple organ failure, and eventually death. Mesenchymal stromal/stem cells (MSCs) are currently one of hopeful approaches in treating COVID-19 considering its anti-inflammatory and immunomodulatory functions. On that account, the number of clinical trials concerning the use of MSCs for COVID-19 has been increasing. However, the number of systematic reviews and meta-analysis that specifically discuss its potential as treatment for the disease is still lacking. Therefore, this review will assess the safety and efficacy of MSC administration in COVID-19 patients.
OBJECTIVES: To pool evidence on the safety and efficacy of MSCs in treating COVID-19 by observing MSC-related adverse effects as well as evaluating its effects in reducing inflammatory response and improving pulmonary function.
DATA SOURCES AND METHODS: Following literature search across six databases and one trial register, full-text retrieval, and screening against eligibility criteria, only eight studies were included for data extraction. All eight studies evaluated the use of umbilical cord-derived mesenchymal stromal/stem cell (UC-MSC), infused intravenously. Of these eight studies, six studies were included in meta-analysis on the incidence of mortality, adverse events (AEs), and serious adverse events (SAEs), and the levels of C-reactive protein (CRP) and interleukin (IL)-6. Meta-analysis on pulmonary function was not performed due to insufficient data.
RESULTS: MSC-treated group showed significantly lower risk of mortality than the control group (p = 0.03). No statistical significance was observed on the incidence of AEs (p = 0.78) and SAEs (p = 0.44), and the levels of CRP (p = 0.06) and IL-6 (p = 0.09).
CONCLUSION: MSCs were safe for use, with lower risk of mortality and no association with AEs. Regarding efficacy, descriptive analysis showed indications of improvement on the inflammatory reaction, lung clearance, and oxygenation status despite the lack of statistical significance in meta-analysis of CRP and IL-6. Nevertheless, more studies are needed for affirmation.
REGISTRATION: This systematic review and meta-analysis was registered on the PROSPERO database (no. CRD42022307730).
Office Three-Dimensional Printed Osteotomy Guide for Corrective Osteotomy in Fibrous Dysplasia

Zamri MF, Ng BW, Jamil K, Abd Rashid AH, Abd Rasid AF

Cureus, 2023 Mar;15(3):e36384.
PMID: 37090315 DOI: 10.7759/cureus.36384

Fibrous dysplasia is a benign condition but can lead to severe long-bone deformities. Three-dimensional (3D) printing technology is a rapidly developing field that has now been popularized to aid surgeons in preoperative planning. We report a case of hip deformity in a 21-year-old woman who suffered from fibrous dysplasia and underwent a corrective osteotomy. We utilized open-source 3D computing software for preoperative planning before producing an osteotomy guide to aid in the operation.
Drivers of HIV self-testing among female sex workers: Findings from a multi-state study in Malaysia

Kim RS, Wickersham JA, Maviglia F, Galka JM, Azwa I, Gautam K, et al.

Front Med (Lausanne), 2023;10:1022746.
PMID: 37089614 DOI: 10.3389/fmed.2023.1022746

BACKGROUND: Although research on HIV self-testing (HIVST) has rapidly increased, few studies have explored HIVST uptake in female sex workers (FSW), and none in Malaysia. Therefore, we endeavored to assess the willingness to use HIVST in this at-risk, vulnerable population.
METHODS: A cross-sectional survey study was conducted among 113 HIV-negative Malaysian FSW in 2017. Participants were recruited using advertisements on social media, flyers, and direct referrals from community-based organizations. Data were collected using self-administered surveys. Multivariable logistic regression was used to identify correlates of willingness to use HIVST.
RESULTS: Nearly a third of participants (30.1%) reported they would be willing to use HIVST. Multivariable analyses adjusting for Malay ethnicity, stable housing, living in Kuala Lumpur (KL), years in sex work, age of first sex work, childhood sexual assault, history of HIV testing, and previously in prison indicated that living in KL [adjusted odds ratio (aOR) = 5.214, p = 0.0137] was associated with a greater willingness to use HIVST. In contrast, having stable housing (aOR = 0.100, p = 0.0064) was negatively associated with willingness to use HIVST.
CONCLUSIONS: Our results indicate that HIVST may potentially enhance the uptake of HIV testing among FSWs living in an urban environment and experiencing unstable housing, but an overall willingness to use HIVST is low. These findings highlight the need for efforts to increase awareness of HIVST among FSWs and additional research on the effective implementation of HIVST for FSW.
Fulltext Curcumin improves the efficacy of cisplatin by targeting cancer stem-like cells through p21 and cyclin D1-mediated tumour cell inhibition in non-small cell lung cancer cell lines

Baharuddin P, Satar N, Fakiruddin KS, Zakaria N, Lim MN, Yusoff NM, et al.

Oncol Rep, 2016 Jan;35(1):13-25.
PMID: 26531053 DOI: 10.3892/or.2015.4371

Natural compounds such as curcumin have the ability to enhance the therapeutic effectiveness of common chemotherapy agents through cancer stem-like cell (CSC) sensitisation. In the present study, we showed that curcumin enhanced the sensitivity of the double-positive (CD166+/EpCAM+) CSC subpopulation in non-small cell lung cancer (NSCLC) cell lines (A549 and H2170) to cisplatin-induced apoptosis and inhibition of metastasis. Our results revealed that initial exposure of NSCLC cell lines to curcumin (10-40 µM) markedly reduced the percentage of viability to an average of ~51 and ~54% compared to treatment with low dose cisplatin (3 µM) with only 94 and 86% in both the A549 and H2170 cells. Moreover, sensitisation of NSCLC cell lines to curcumin through combined treatment enhanced the single effect induced by low dose cisplatin on the apoptosis of the double-positive CSC subpopulation by 18 and 20% in the A549 and H2170 cells, respectively. Furthermore, we found that curcumin enhanced the inhibitory effects of cisplatin on the highly migratory CD166+/EpCAM+ subpopulation, marked by a reduction in cell migration to 9 and 21% in the A549 and H2170 cells, respectively, indicating that curcumin may increase the sensitivity of CSCs to cisplatin-induced migratory inhibition. We also observed that the mRNA expression of cyclin D1 was downregulated, while a substantial increased in p21 expression was noted, followed by Apaf1 and caspase-9 activation in the double-positive (CD166+/EpCAM+) CSC subpopulation of A549 cells, suggested that the combined treatments induced cell cycle arrest, therefore triggering CSC growth inhibition via the intrinsic apoptotic pathway. In conclusion, we provided novel evidence of the previously unknown therapeutic effects of curcumin, either alone or in combination with cisplatin on the inhibition of the CD166+/EpCAM+ subpopulation of NSCLC cell lines. This finding demonstrated the potential therapeutic approach of using curcumin that may enhance the effects of cisplatin by targeting the CSC subpopulation in NSCLC.

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