Displaying publications 101 - 120 of 126 in total

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  1. Ismail NFF, Neoh CF, Lim SM, Abdullah AH, Mastuki MF, Ramasamy K, et al.
    Medicine (Baltimore), 2017 Jul;96(30):e7511.
    PMID: 28746195 DOI: 10.1097/MD.0000000000007511
    INTRODUCTION: Asian countries have a variety of ethnic groups and culture that provide their own traditional treatment in health care. Facial candling appears to be one of the popular traditional treatments in Southeast Asian. The complementary medicine practitioners promote that the facial candling treatment would help in reducing the symptoms of allergic rhinitis and other problems related to sinus. Due to the lack of evidence available, the effectiveness of this treatment method and its mechanism, however, remains unknown. The objective of this research is therefore to study impact of facial candling on inflammatory mediators, substance P (SP), symptoms severity, and quality of life (QoL) in allergic rhinitis patients.

    METHOD AND ANALYSIS: A randomized, nonblinded, controlled trial will be carried out by recruiting a total of 66 eligible allergic rhinitis patients who fulfill the inclusion criteria from a university health center. The subjects will be randomly assigned into 2 groups: intervention group receiving facial candling treatment and control group (no treatment given). Samples of blood and nasal mucus will be collected right before and after intervention. Samples collected will be analyzed. The primary outcomes are the changes in the level of SP in both blood and mucus samples between both groups. The secondary outcomes include the levels of inflammatory mediators (ie, tumor necrosis factor alpha, interleukin (IL)-3, IL-5, IL-6, IL-10, and IL-13) and the severity of allergic rhinitis symptoms as measured by a visual analogous scale and QoL using the Rhinitis Quality of Life Questionnaire (RQLQ).

    ETHICAL AND TRIAL REGISTRATION: The study protocols are approved from the Ethical and Research Committee of the Universiti Teknologi MARA (REC/113/15). The trial is registered under the Australia New Zealand Clinical Trial Registry (ACTRN12616000299404). The trial was registered on 03/07/2016 and the first patient was enrolled on 10/12/2016.

    CONCLUSION: Facial candling is one of the unique treatments using candles to reduce the severity of symptoms and inflammation. This is the first ever study conducted on facial candling that will give rise to new knowledge underlying the effects of facial candling on severity of symptoms and inflammation relief mechanism mediated by substance P and inflammatory mediators.

  2. Ismail NFF, Neoh CF, Lean QY, Abdullah AH, Lim SM, Ramasamy K, et al.
    J Pharm Bioallied Sci, 2018 12 21;10(4):199-207.
    PMID: 30568377 DOI: 10.4103/JPBS.JPBS_33_18
    Aims: Facial candling is one of the traditional treatments that is claimed to be able to help in curing or reducing various allergy and inflammation conditions such as allergic rhinitis. We aimed to explore the perceptions of participants with allergic rhinitis toward their disease conditions and facial candling treatment.

    Materials and Methods: The study used a qualitative exploratory design, comprising 12 in-depth interviews. A semi-structured topic guide was used to explore all relevant aspects of the topic, which were audio recorded, transcribed verbatim. All the interviews were conducted in a few beauty salons in purposively selected city areas in the state of Kedah, Malaysia.

    Results: Of the 12 patients, seven (58%) reported a positive experience of facial candling treatment, with improvement in the condition of their allergic rhinitis. Specific themes about the experience of facial candling treatment that were identified within the transcript data included knowledge about facial candling, options for disease treatment, effectiveness of facial candling, sources of information, comparison, application of treatment, treatment budget, and safety. The major strength lies in the fact that reasons for using facial candling were uncovered from the perspectives of people with allergic rhinitis through the in-depth interviews.

    Conclusions: The motives of these participants for using facial candling are mainly due to cultural influence and its low cost of treatment. There were mixed responses from the participants about the usefulness of facial candling. Most of the respondents had not assessed the safety of prolonged use of facial candling and regarded it as a safe procedure as this has been practiced for generations.

  3. Lim SM, Choo JM, Li H, O'Rielly R, Carragher J, Rogers GB, et al.
    Foods, 2021 Jan 21;10(2).
    PMID: 33494480 DOI: 10.3390/foods10020220
    High amylose wheat (HAW) contains more resistant starch than standard amylose wheat (SAW) and may have beneficial effects on gastrointestinal health. However, it is currently unclear whether these effects differ according to the level of HAW included in the diet or between males and females. Male and female C57BL/6 mice (n = 8/group/sex) were fed SAW65 (65% SAW; control), HAW35 (35% HAW), HAW50 (50% HAW) or HAW65 (65% HAW) diet for eight weeks. Female but not male, mice consuming any amount of HAW exhibited accelerated gastric emptying compared to SAW65 group. In both sexes, relative colon weights were higher in the HAW65 group compared to SAW65 group and in females, relative weights of the small intestine and cecum were also higher in the HAW65 group. In females only, colonic expression of Pyy and Ocln mRNAs were higher in the HAW65 group compared to HAW35 and HAW50 groups. In both sexes, mice consuming higher amounts of HAW (HAW50 or HAW65) had increased fecal bacterial load and relative abundance of Bacteroidetes phylum and reduced relative abundance of Firmicutes compared to SAW65 group. These data are consistent with a beneficial impact of HAW on gastrointestinal health and indicate dose-dependent and sex-specific effects of HAW consumption.
  4. Rehiman SH, Lim SM, Lim FT, Chin AV, Tan MP, Kamaruzzaman SB, et al.
    Int J Neurosci, 2020 Dec 15.
    PMID: 33280461 DOI: 10.1080/00207454.2020.1860038
    Objective: Alzheimer's disease (AD), the commonest form of dementia which is characterized by progressive decline in cognitive function, can only be definitively diagnosed after death. Although biomarkers may aid diagnosis, currently available AD biomarkers, which are predominantly based on cerebrospinal fluid and neuroimaging facilities, are either invasive or costly. Blood-based biomarkers for AD diagnosis are highly sought after due to its practicality at the clinic. This study was undertaken to determine the differential protein expression in plasma amongst Malaysian AD, mild cognitive impairment (MCI) and non-AD individuals. Methods: A proteomic approach which utilized two-dimensional differential in gel electrophoresis (2 D DIGE) was performed for blood samples from 15 AD, 14 MCI and 15 non-AD individuals. Results: Mass spectrometry (MS)-based protein identification via MALDI ToF/ToF showed that fibrinogen-β-chain (spot 64) and fibrinogen-γ-chain (spot 91) with differential expression ratio >1.5 were significantly upregulated (p 
  5. O'Rielly R, Li H, Lim SM, Yazbeck R, Kritas S, Ullrich SS, et al.
    Nutrients, 2020 Aug 14;12(8).
    PMID: 32823899 DOI: 10.3390/nu12082446
    Chronic isoleucine supplementation prevents diet-induced weight gain in rodents. Acute-isoleucine administration improves glucose tolerance in rodents and reduces postprandial glucose levels in humans. However, the effect of chronic-isoleucine supplementation on body weight and glucose tolerance in obesity is unknown. This study aimed to investigate the impact of chronic isoleucine on body weight gain and glucose tolerance in lean and high-fat-diet (HFD) induced-obese mice. Male C57BL/6-mice, fed a standard-laboratory-diet (SLD) or HFD for 12 weeks, were randomly allocated to: (1) Control: Drinking water; (2) Acute: Drinking water with a gavage of isoleucine (300 mg/kg) prior to the oral-glucose-tolerance-test (OGTT) or gastric-emptying-breath-test (GEBT); (3) Chronic: Drinking water with 1.5% isoleucine, for a further six weeks. At 16 weeks, an OGTT and GEBT was performed and at 17 weeks metabolic monitoring. In SLD- and HFD-mice, there was no difference in body weight, fat mass, and plasma lipid profiles between isoleucine treatment groups. Acute-isoleucine did not improve glucose tolerance in SLD- or HFD-mice. Chronic-isoleucine impaired glucose tolerance in SLD-mice. There was no difference in gastric emptying between any groups. Chronic-isoleucine did not alter energy intake, energy expenditure, or respiratory quotient in SLD- or HFD-mice. In conclusion, chronic isoleucine supplementation may not be an effective treatment for obesity or glucose intolerance.
  6. Rehiman SH, Lim SM, Neoh CF, Majeed ABA, Chin AV, Tan MP, et al.
    Ageing Res Rev, 2020 07;60:101066.
    PMID: 32294542 DOI: 10.1016/j.arr.2020.101066
    In order to gauge the impact of proteomics in discovery of Alzheimer's disease (AD) blood-based biomarkers, this study had systematically reviewed articles published between 1984-2019. Articles that fulfilled the inclusion criteria were assessed for risk of bias. A meta-analysis was performed for replicable candidate biomarkers (CB). Of the 1651 articles that were identified, 17 case-control and two cohort studies, as well as three combined case-control and longitudinal designs were shortlisted. A total of 207 AD and mild cognitive impairment (MCI) CB were discovered, with 48 reported in >2 studies. This review highlights six CB, namely alpha-2-macroglobulin (α2M)ps, pancreatic polypeptide (PP)ps, apolipoprotein A-1 (ApoA-1)ps, afaminp, insulin growth factor binding protein-2 (IGFBP-2)ps and fibrinogen-γ-chainp, all of which exhibited consistent pattern of regulation in >three independent cohorts. They are involved in AD pathogenesis via amyloid-beta (Aβ), neurofibrillary tangles, diabetes and cardiovascular diseases (CVD). Meta-analysis indicated that ApoA-1ps was significantly downregulated in AD (SMD = -1.52, 95% CI: -1.89, -1.16, p 
  7. Lai HY, Foo LL, Lim SM, Yong CF, Loh PS, Chaw SH, et al.
    Clin Auton Res, 2020 Feb;30(1):53-60.
    PMID: 29196938 DOI: 10.1007/s10286-017-0485-8
    PURPOSE: Comparison of hemodynamic profiles and pain scores in diabetic patients undergoing diabetic foot surgery receiving peripheral nerve block (PNB) or spinal anesthesia [subarachnoid block (SAB)].

    METHODS: This was a prospective, randomised controlled trial. We recruited diabetic patients aged > 18 years, American Society of Anesthesiologists class II-III, who were scheduled for unilateral diabetic foot surgery below the knee. All patients were assessed for autonomic dysfunction using the Survey of Autonomic Symptoms score. Participants were randomly assigned to receive either PNB or SAB for the surgery. Hemodynamic data, including usage of vasopressors, were recorded at 5-min intervals for up to 1 h after the induction of anesthesia. Pain scores were recorded postoperatively, and follow-up was done via telephone 6 months later.

    RESULTS: Compared to the PNB group, the SAB group had a larger number of patients with significant hypotension (14 vs. 1; p = 0.001) and more patients who required vasopressor boluses (6 vs. 0 patients). Compared to SAB group, the patients in the PNB group had a longer postoperative pain-free duration (9 vs. 4.54 h; p = 0.002) and lower pain scores 1 day after surgery (3.63 vs. 4.69; p = 0.01).

    CONCLUSION: Peripheral nerve block should be considered, whenever possible, as the first option of anesthesia for lower limb surgery in diabetic patients as it provides hemodynamic stability and superior postoperative pain control compared to SAB.

    TRIAL REGISTRATION: Clinical trial registry: ClinicalTrials.gov. ID NCT02727348.

  8. Rashidah NH, Lim SM, Neoh CF, Majeed ABA, Tan MP, Khor HM, et al.
    Ageing Res Rev, 2022 Dec;82:101744.
    PMID: 36202312 DOI: 10.1016/j.arr.2022.101744
    This systematic review appraised previous findings on differential gut microbiota composition and intestinal permeability markers between frail and healthy older adults. A literature search was performed using PubMed, Scopus, ScienceDirect and the Cochrane Library. Relevant studies were shortlisted based on inclusion and exclusion criteria as well as assessed for risk of bias. The primary outcome was the differential composition of gut microbiota and/ or intestinal permeability markers between frail and healthy older adults. A total of 10 case-control studies and one cohort study were shortlisted. Based on consistent findings reported by more than one shortlisted study, the microbiota of frail older adults was characterised by decreased phylum Firmicutes, with Dialister, Lactobacillus and Ruminococcus being the prominent genera. Healthy controls, on the other hand, exhibited higher Eubacterium at the genera level. In terms of intestinal permeability, frail older adults were presented with increased serum zonulin, pro-inflammatory cytokines (TNF-α, HMGB-1, IL-6, IL1-ra, MIP-1β) and amino acids (aspartic acid and phosphoethanolamine) when compared to healthy controls. Altogether, frail elderlies had lower gut microbiota diversity and lower abundance of SCFA producers, which may have led to leaky guts, upregulated pro-inflammatory cytokines, frailty and sarcopenia.
  9. Jang JH, Gomez RD, Bumbea H, Nogaieva L, Wong LLL, Lim SM, et al.
    EJHaem, 2023 Feb;4(1):26-36.
    PMID: 36819188 DOI: 10.1002/jha2.632
    Treatment of paroxysmal nocturnal haemoglobinuria (PNH) includes the monoclonal antibody eculizumab. This randomised, double-blind, multi-national cross-over Phase III study in PNH patients aimed to demonstrate the equivalence of the proposed eculizumab biosimilar SB12 and reference eculizumab (Soliris, ECU). PNH patients with lactate dehydrogenase (LDH) ≥1·5× upper limit of normal were randomised into treatment sequences SB12-ECU or ECU-SB12. Four weekly infusions of 600 mg eculizumab were followed by fortnightly infusions of 900 mg until week 50 (ECU/SB12 cross-over at week 26). Primary endpoints were LDH at week 26 and the time-adjusted area under the effect curve (AUEC) of LDH over weeks 14‒26 and 40‒52. Among 46 patients (92%) who completed the study, the least squares mean (LSM) difference in LDH at week 26 (34·48; 95% confidence interval [CI] -47·66‒116·62 U/l) and geometric LSM ratio of time-adjusted AUEC of LDH (1·08; 90% CI 0·95‒1·23) were within pre-defined equivalence margins. Mean numbers of transfused red blood cell units, other secondary endpoints, pharmacokinetics, and pharmacodynamics were comparable. No patients developed anti-drug antibodies. Treatment-emergent adverse events were reported in 72% and 68% of patients in the SB12 and ECU treatment groups, respectively. The results demonstrate equivalence of SB12 to ECU and support SB12-use in PNH patients.
  10. Karim SM, Lim SM, Ilancheran A, Ratnam SS, Ang LT, Ng KH, et al.
    Ann Acad Med Singap, 1982 Oct;11(4):503-7.
    PMID: 7165271
    Prostaglandin E2 administered orally and combined with amniotomy was used for induction of labour at or near term in 1533 patients. The study was carried out as a collaborative project between the University Departments of Obstetrics and Gynaecology in Singapore, Medan (Indonesia) and Kuala Lumpur (Malaysia). The overall success rates for Medan, Kuala Lumpur and Singapore were 95.6%, 88.1% and 84.7% respectively.
  11. Lai LL, Teh MS, Beh ZY, Lim WL, Lim SM, Soh WQ, et al.
    World J Surg, 2024 Dec;48(12):2799-2810.
    PMID: 39444164 DOI: 10.1002/wjs.12364
    INTRODUCTION: This study aims to establish, execute, and assess the effectiveness of a perioperative enhanced recovery after surgery (ERAS) clinical care pathway in breast reconstruction patients with LD flap breast cancer treatment. The goal is to improve early recovery outcomes, reduce hospitalization time, and enhance patient satisfaction by implementing a standardized approach to postoperative care.

    METHODS: This study was conducted at the University of Malaya Medical Center. The outcomes of 21 breast cancer patients who underwent autologous reconstructive breast surgery with the latissimus dorsi (LD) flap within six months before the implementation of the ERAS pathway (pre-ERAS) were compared with 26 patients who underwent the same surgery with the ultrasound-guided erector spinae plane (ESP) block for the (ERAS protocol implementation) cohort. The study was conducted from November 2019 to October 2020. The length of hospital stay, amount of analgesic usage, and incidence of postoperative nausea vomiting (PONV) were recorded.

    RESULTS: The implementation of the ERAS clinical care pathway resulted in shorter hospital stays compared with the preceding care. On average, ERAS patients were mostly discharged on Day 2 post-surgery, whereas pre-ERAS patients were mostly discharged on Day 7. ERAS patients had a lower incidence of PONV from Days 1 to 5, starting with 88.5% not experiencing the condition on Days 1 and 2 and increasing to 100% on Day 5. All pre-ERAS patients experienced PONV in the first 5 days post-surgery. Fewer ERAS patients required antiemetics post-surgery (88.5%) compared with pre-ERAS patients (42.9%).

    CONCLUSION: The implementation of the ERAS protocol as part of clinical care in autologous reconstructive breast surgery with the LD flap can improve recovery by shortening hospital stay, decreasing the use of analgesia, and alleviating PONV.

  12. Hor JY, Lim TT, Cheng MC, Chia YK, Wong CK, Lim SM, et al.
    J Neuroimmunol, 2018 04 15;317:100-102.
    PMID: 29395322 DOI: 10.1016/j.jneuroim.2018.01.011
    Thymoma is associated with a wide spectrum of autoimmune paraneoplastic syndromes, though it is uncommon for multiple paraneoplastic syndromes to be present in a single individual. We report a rare case of an elderly gentleman who was found to have thymoma-associated myasthenia gravis and LGI1-encephalitis with myokymia, who presented with nephrotic syndrome (minimal change glomerulopathy) after thymectomy. The latter two paraneoplastic syndromes had manifested when prednisolone was tapered down to low dose. This case serves to remind neurologists that apart from paraneoplastic neurological manifestations, thymoma may also be associated with renal disease. Nephropathy in myasthenia patients with thymoma should be properly evaluated, as it is treatable with immunotherapy, and it may even occur post-thymectomy.
  13. Enche Ady CNA, Lim SM, Teh LK, Salleh MZ, Chin AV, Tan MP, et al.
    J Neurosci Res, 2017 Oct;95(10):2005-2024.
    PMID: 28301062 DOI: 10.1002/jnr.24048
    The rapid increase in the older population has made age-related diseases like Alzheimer's disease (AD) a global concern. Given that there is still no cure for this neurodegenerative disease, the drastic growth in the number of susceptible individuals represents a major emerging threat to public health. The poor understanding of the mechanisms underlying AD is deemed the greatest stumbling block against progress in definitive diagnosis and management of this disease. There is a dire need for biomarkers that can facilitate early diagnosis, classification, prognosis, and treatment response. Efforts have been directed toward discovery of reliable and distinctive AD biomarkers but with very little success. With the recent emergence of high-throughput technology that is able to collect and catalogue vast datasets of small metabolites, metabolomics offers hope for a better understanding of AD and subsequent identification of biomarkers. This review article highlights the potential of using multiple metabolomics platforms as useful means in uncovering AD biomarkers from body fluids. © 2017 Wiley Periodicals, Inc.
  14. Samah S, Neoh CF, Wong YY, Hassali MA, Shafie AA, Lim SM, et al.
    Res Social Adm Pharm, 2017 11;13(6):1135-1141.
    PMID: 27825607 DOI: 10.1016/j.sapharm.2016.10.017
    BACKGROUND: Quality of life (QoL) assessment provides valuable outcome to support clinical decision-making, particularly for patients with chronic diseases that are incurable. A brief, 15-item diabetes-specific tool [i.e. Diabetes Quality of Life-Brief Clinical Inventory (DQoL-BCI)] is known to be developed in English and validated for use in clinical practice. This simplified tool, however, is not readily available for use in the Malaysian setting.

    OBJECTIVE: To translate the DQoL-BCI into a Malaysian version and to assess its construct validity (factorial validity, convergent validity and discriminant validity), reliability (internal consistency) and floor and ceiling effects among the Malaysian diabetic population.

    MATERIAL AND METHODS: A forward-backward translation, involving professional translators and experts with vast experience in translation of patient reported outcome measures, was conducted. A total of 202 patients with Type 2 diabetes mellitus (T2DM) who fulfilled the inclusion criteria were invited to complete the translated DQoL-BCI. Data were analysed using SPSS for exploratory factor analysis (EFA), convergent and discriminant validity, reliability and test-retest, and AMOS software for confirmatory factor analysis (CFA).

    RESULTS: Findings from EFA indicated that the 4-factor structure of the Malaysian version of DQoL-BCI was optimal and explained 50.9% of the variance; CFA confirmed the 4-factor model fit. There was negative, moderate correlation between the scores of DQoL-BCI (Malaysian version) and EQ-5D-3L utility score (r = -0.329, p = 0.003). Patients with higher glycated haemoglobin levels (p = 0.008), diabetes macrovascular (p = 0.017) and microvascular (p = 0.013) complications reported poorer QoL. Cronbach's alpha coefficient and intraclass coefficient correlations (range) obtained were 0.703 and 0.86 (0.734-0.934), indicating good reliability and stability of the translated DQoL-BCI.

    CONCLUSION: This study had validated the linguistic and psychometric properties of DQoL-BCI (Malaysian version), thus providing a valid and reliable brief tool for assessing the QoL of Malaysian T2DM patients.

  15. Wan Sulaiman WA, Kamtchum-Tatuene J, Mohamed MH, Ramachandran V, Ching SM, Sazlly Lim SM, et al.
    Indian J Med Res, 2019 06;149(6):706-714.
    PMID: 31496523 DOI: 10.4103/ijmr.IJMR_454_17
    Onchocerciasis and lymphatic filariasis (LF) are human filarial diseases belonging to the group of neglected tropical diseases, leading to permanent and long-term disability in infected individuals in the endemic countries such as Africa and India. Microfilaricidal drugs such as ivermectin and albendazole have been used as the standard therapy in filariasis, although their efficacy in eliminating the diseases is not fully established. Anti-Wolbachia therapy employs antibiotics and is a promising approach showing potent macrofilaricidal activity and also prevents embryogenesis. This has translated to clinical benefits resulting in successful eradication of microfilarial burden, thus averting the risk of adverse events from target species as well as those due to co-infection with loiasis. Doxycycline shows potential as an anti-Wolbachia treatment, leading to the death of adult parasitic worms. It is readily available, cheap and safe to use in adult non-pregnant patients. Besides doxycycline, several other potential antibiotics are also being investigated for the treatment of LF and onchocerciasis. This review aims to discuss and summarise recent developments in the use of anti-Wolbachia drugs to treat onchocerciasis and LF.
  16. Hamdan NKA, Lean QY, Neoh CF, Abdullah AH, Lim SM, Ramasamy K, et al.
    PMID: 32831870 DOI: 10.1155/2020/5713134
    Introduction: Facial candling is a traditional method used for relieving symptoms of allergic rhinitis (AR). This study aims to investigate the knowledge and perception of facial candling in a sample of staff and students in a public university in Malaysia.

    Methods: An online questionnaire survey method was used. Based on sample size calculation, a total of 1,508 UiTM staff and students from ten selected campuses of Universiti Teknologi MARA (UiTM) were invited to participate in this survey. An up-to-date e-mail list of staff in the selected campuses was used as the sampling frame for the study, whereas the students were recruited from the official university student Facebook portal.

    Results: A total of 788 respondents participated in this survey, 72.2% of them knew about facial candling, though only 35.4% had tried the treatment. Approximately one-fifth of respondents agreed that facial candling might treat AR. It was found that a higher number of users than nonusers agreed that facial candling was a traditional medicine (78.9% vs 55.0%); could be used on the face and ears (83.5% vs 45.4%); and could be self-administered at home (83.5 vs 45.4%). Interestingly, more than half of them were uncertain about its long-term effects and adverse reactions.

    Conclusion: This study confirms the facial candling use among patients with AR although the percentage is low. The patients and general public need to be better informed about the use of facial candling in AR and its associated risks.

  17. Xu XJ, Myint PK, Lee SWH, Ramasamy K, Lim SM, Majeed ABA, et al.
    Int J Clin Pharm, 2024 Dec;46(6):1453-1463.
    PMID: 39264491 DOI: 10.1007/s11096-024-01791-1
    BACKGROUND: While the effects of anticholinergic drug use have been increasingly highlighted, trends in anticholinergic use remain poorly understood.

    AIM: To determine the changes in frequency and pattern of anticholinergic drug use within a low- and middle-income country.

    METHOD: Comparisons were made between population-based datasets collected from Malaysian residents aged 55 years and older in 2013-15 and 2020-22. Anticholinergic exposure was determined using the anticholinergic cognitive burden (ACB) tool. Drugs with ACB were categorised according to the Anatomical Therapeutic Chemical (ATC) classification.

    RESULTS: A total number of 5707 medications were recorded from the 1616 participants included in the 2013-15 dataset. A total number of 6175 medications were recorded from 2733 participants in 2020-22. Two hundred and ninety-three (18.1%) and 280 (10.2%) participants consumed ≥ 1 medication with ACB ≥ 1 in 2013-15 and 2020-22 respectively. The use of nervous system drugs with ACB had increased (27 (0.47%) versus 39 (0.63%). The use of ACB drugs in the cardiovascular (224 (3.9%) versus 215 (3.4%)) and alimentary tract and metabolism (30 (0.52%) versus 4 (0.06%)) classes had reduced over time. Participants in 2020-22 were significantly less likely than those in 2013-15 to have total ACB = 1 - 2 (odds ratio [95% confidence interval] = 0.473[0.385-0.581]) and ACB ≥ 3 (0.251[0.137 - 0.460]) compared to ACB = 0 after adjustment for potential confounders (p 

  18. Luo Y, Chen Y, Ai C, Huang X, Perna F, Kale BJ, et al.
    Transl Cancer Res, 2024 Nov 30;13(11):6273-6281.
    PMID: 39697751 DOI: 10.21037/tcr-24-1543
    BACKGROUND: Lenalidomide-based therapies are recommended as first-line treatment for multiple myeloma (MM) patients, regardless of the transplant eligibility. Resistance to lenalidomide is a clinical problem that urgently needs to be addressed. The expression of poly(ADP-ribose) polymerase 1 (PARP1) is abnormally high in a variety of tumor tissues including MM. However, in lenalidomide-resistant MM, it is not yet known whether the abnormally high expression of PARP1 is involved in the occurrence of drug resistance, and whether the inhibition of PARP1 can reverse lenalidomide resistance. The aim of this study was to investigate the mechanism of PARP1 promoting lenalidomide-resistant in MM patients.

    METHODS: Samples of bone marrow from patients with MM who were sensitive or resistant to lenalidomide were collected. The expression levels of PARP1 at the messenger RNA and protein levels were detected through polymerase chain reaction and western blot. MM cell lines were cultivated in vitro, cell lines resistant to lenalidomide were screened out, and the expression levels of PARP1 in the resistant cell lines were detected. The apoptosis level was also detected in the lenalidomide-resistant MM cell lines treated with a PARP1 inhibitor. The proliferation rates of the two groups of cells at different time points were evaluated by mono-methyl terephthalate (MMT) experiments. Finally, the effect of PARP1 on the proliferation of lenalidomide-resistant MM through the microRNA-192-5p-AKT signaling pathway was analyzed.

    RESULTS: In the lenalidomide-resistant cell lines, the expression level of PARP1 was higher, the proliferation more rapid, and the apoptosis rate was lower than lenalidomide-sensitive cell lines. Additionally, the activated AKT pathway was suppressed by downregulating the expression of microRNA-192-5p. MM resistance can be inhibited to some extent by impacting PARP1.

    CONCLUSIONS: PARP1 is involved in the production of lenalidomide resistance in MM, and could serve as a potential target for the treatment of MM in the future.

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