1.Noggin alleviates neuropathic pain by regulating microglial polarization and remodeling iron homeostasis via a STAT3-dependent pathway.
Wenjuan ZHANG ; Lin YANG ; Ran ZHANG
Journal of Central South University(Medical Sciences) 2025;50(4):602-614
OBJECTIVES:
Pain sensitization, as a core feature of neuropathic pain (NP), is closely associated with inflammatory imbalance within the central nervous system. To investigate the effects of intrathecal injection of noggin (NOG) on mechanical hypersensitivity, microglial (MG) activation and polarization, and iron metabolism in a spinal nerve ligation (SNL)-induced rat model of NP, and to explore the role of signal transducer and activator of transcription 3 (STAT3) in MG phenotypic transformation.
METHODS:
Sixty-six Sprague-Dawley (SD) rats were randomly divided into 3 groups: Sham, SNL, and SNL+NOG. Paw withdrawal threshold (PWT) was assessed using von Frey filaments. Western blotting and real-time polymerase chain reaction (RT-PCR) were used to detect spinal cord expression of MG activation marker CD11b, STAT3, phosphorylated STAT3 (p-STAT3), M1 polarization markers [CD86, CD32, interleukin (IL)-1β], tumor necrosis factor-alpha (TNF-α), and CC chemokine receptor 2 (CCR2), M2 markers [CD204, CD163, CX3C chemokine receptor 1 (CX3CR1), IL-10, and arginase-1 (ARG-1)], and iron metabolism-related proteins including ferroportin (FPN, gene: SLC40A1), hepcidin (gene: HAMP), transferrin receptor (gene: TFRC), and divalent metal transporter 1 (DMT-1, gene: SLC11A2). p-STAT3 localization in MGs was visualized via immunofluorescence. In vitro, primary MGs were divided into Control, bone morphogenetic protein-4 (BMP4), and BMP4+Stattic (STAT3 inhibitor) groups to examine the effects of STAT3 inhibition on MG activation, polarization, and iron regulation.
RESULTS:
In vivo, compared with the Sham group, the SNL and SNL+NOG groups exhibited significantly decreased PWT (P<0.05), elevated spinal CD11b and p-STAT3 protein levels (all P<0.05), increased M1 markers (CD86, CD32, IL-1β, TNF-α, and CCR2) (all P<0.05), and decreased M2 markers (CD204 protein; mRNA of CD204, ARG-1) (all P<0.05). Hepcidin protein and mRNA levels of HAMP, SLC11A2, and TFRC were significantly elevated, while FPN protein and SLC40A1 mRNA were reduced (all P<0.05). Compared to SNL alone, the SNL+NOG group showed increased PWT, decreased CD11b, p-STAT3, and M1 marker expression (except TNF-α), increased M2 marker expression, reduced hepcidin and HAMP levels, and increased FPN and SLC40A1 expression (all P<0.05). In vitro, BMP4 treatment increased CD11b, STAT3, p-STAT3, CD86, and hepcidin levels, while reducing CD204 and FPN (all P<0.05). Inhibition STAT3 with Stattic reversed these changes (all P<0.05).
CONCLUSIONS
NOG alleviates SNL-induced NP by antagonizing the STAT3 signaling pathway, thereby rebalancing microglial polarization and restoring iron metabolism.
Animals
;
Neuralgia/drug therapy*
;
Rats, Sprague-Dawley
;
Microglia/cytology*
;
STAT3 Transcription Factor/metabolism*
;
Rats
;
Iron/metabolism*
;
Male
;
Signal Transduction/drug effects*
;
Carrier Proteins/therapeutic use*
;
Homeostasis/drug effects*
;
Spinal Cord/metabolism*
3.Bacteraemia in Haematopoietic Stem Cell Transplant Recipients in a Single Tertiary Referral Centre
NURUL IMAN P ; RAMLIZA R ; WAN FARIZA WJ ; SHAMSUL AZHAR S ; NOR AZIMAH I ; FADILAH SAW
Medicine and Health 2019;14(2):60-76
Bacteraemia is a common and one of the serious complications in haematopoietic stem cell transplantation (HSCT). To date, there are no published data on antibiotic resistance and clinical outcome among HSCT recipients in Malaysia. The aims of the present study was to analyse the prevalence, antibiotic resistance and clinical outcome of bacteraemia in HSCT recipients within 100 days following transplantation. We retrospectively analysed the prevalence, antibiotic resistance pattern and mortality rate of early bacteraemia among HSCT recipients in a single centre over a 5-year period (2013-2017). Thirty patients of 85 HSCT recipients developed bacteraemia with 40 positive cultures resulting in prevalence of 47% (40/85). Gram negative bacteria (GNB) accounted for 60.5% of total isolates. Enterobacteriaceae and Coagulase negative Staphylococcus (CoNS) were the commonest pathogens isolated. GNB showed a high resistance rate to ciprofloxacin. Only 30% of recipients responded to first line empirical antibiotics for febrile neutropenia (FN). The mortality rate was 13.3% (4/30), of which 50% was attributed to multi-drug resistance (MDR) Acinetobacter and 25% to extended spectrum beta-lactamase (ESBL) Enterobacteriaceae. Bacteraemia is a frequent and life-threatening early complication among HSCT recipients with MDR GNB being the commonest cause of mortality. The high rate of resistance to ciprofloxacin and failure of the first line empirical antibiotics to treat FN calls for a thorough evaluation of the current antibiotic prophylaxis and empirical treatment protocols. These findings have important clinical implications regarding the use and selection of both prophylactic and empiric antibiotic regimens to treat FN.
4.Breast cancer with dermatomyositis as initial presentation
The Medical Journal of Malaysia 2018;73(1):44-45
Patients with breast cancer normally present with breastlump or abnormal mammogram. Dermatomyositis is rarelythe first presentation. We present a case of a 63-year-oldwoman who had generalised dermatitis, progressive fatigueand muscle weakness. She was first diagnosed asdermatomyositis and subsequently breast cancer. Her rashand muscle weakness progressed drastically over a month.Tumescent mastectomy and axillary surgery was performed,which led to gradual regression of her dermatomyositis oversix months. This case report emphasized in the benefit ofearly diagnosis and treatment of dermatomyositis andbreast cancer. Pros and cons of tumescent mastectomy isdiscussed as well.
5.A Survey of Osteoporosis and Breast Cancer Risk Perception among Menopausal and Postmenopausal Women in Hong Kong.
Louis WC CHOW ; Michael MC CHEUNG ; Jennifer WJ CHU ; Ivy CF LI
Journal of Menopausal Medicine 2017;23(2):102-107
OBJECTIVES: A lack of understanding in menopausal and postmenopausal women's (PMW) risk perception towards osteoporosis and breast cancer still exists, which is explored in this study. This information might allow health professionals to conduct interventions to improve health behaviors before menopause-related diseases are imminent. METHODS: Between 10 December 2015 and 31 January 2016, 573 menopausal or PMW were successfully interviewed on 17 questions, comprising separate sections for osteoporosis and breast cancer. The target respondents were menopausal or PMW aged 45 to 60 years, with no previous diagnosis of osteoporosis or breast cancer, who attended private clinics across Hong Kong for annual physical examination. RESULTS: Regarding menopausal issues, the top three concerns were osteoporosis and fracture (72%), breast cancer (44%), and sleep disorder/insomnia/headache (40%). Among 314 respondents (55%) who tried to prevent osteoporosis, 74% of them began to do it after they were 40 years old. On the other hand, 65% of respondents never had a bone density test. For respondents who said “I'm too young, so I don't need to check”, their mean age was 52 years old. Ninety percent of respondents mistakenly believed that regular breast examination, regular breast massage, drink soy milk, or vaccine can prevent breast cancer. CONCLUSIONS: This survey revealed osteoporosis and breast cancer as the top concerns among menopausal and PMW in Hong Kong. Inadequate health behaviors and misconceptions still exist despite widespread health education in the recent years.
Bone Density
;
Breast Neoplasms*
;
Breast*
;
Diagnosis
;
Female
;
Hand
;
Health Behavior
;
Health Education
;
Health Occupations
;
Hong Kong*
;
Humans
;
Massage
;
Osteoporosis*
;
Physical Examination
;
Soy Milk
;
Surveys and Questionnaires
6.Tentorial Dural Arteriovenous Fistulas: A Single-Center Cohort of 12 Patients.
HG KORTMAN ; I BOUKRAB ; G BLOEMSMA ; JP PELUSO ; M SLUZEWSKI ; B VAN DER POL ; GN BEUTE ; CB MAJOIE ; WJ VAN ROOIJ
Journal of Cerebrovascular and Endovascular Neurosurgery 2017;19(4):284-290
OBJECTIVE: Tentorial dural arteriovenous fistulas usually drain into cortical veins and often present with hemorrhage. Treatment goal is occlusion of the draining vein, either by surgery or endovascular techniques. We present the multimodality treatment results of 12 patients with tentorial dural arteriovenous fistulas. MATERIALS AND METHODS: Between January 2007 and January 2017, 12 consecutive patients with tentorial dural arteriovenous fistulas were treated. There were 11 men and 1 woman with a mean age of 62 years (range 44–85). Clinical presentation was hemorrhage in 8 (67%), pulsatile tinnitus in 2 (17%) and an incidental finding in 2 (17%). The fistula location was at the tentorium cerebelli in 5 (42%), the torcula Herophilii in 4 (33%) and petroclival in 3 (25%). RESULTS: In 11 patients, arterial embolization with Onyx or PHIL was the primary treatment. Complete obliteration was achieved in one session in 5 (45%) and in 2 sessions in 4 (36%). In 2 patients additional surgery was needed. Primary surgery was performed in 1 patient followed by endovascular coil occlusion via the venous route. One patient with exclusive pial feeders from the posterior inferior cerebellar artery had a clinically silent P3 occlusion during trans arterial embolization. Finally, all 12 fistula were completely occluded, confirmed with angiography after 8–12 weeks. There were no permanent procedural complications. CONCLUSION: Patients with tentorial dural arteriovenous fistulas were effectively and safely cured with a strategy of endovascular treatment with various techniques and surgery. Surgical and endovascular techniques are complementary in the treatment of these challenging vascular disorders.
Angiography
;
Arteries
;
Central Nervous System Vascular Malformations*
;
Cohort Studies*
;
Endovascular Procedures
;
Female
;
Fistula
;
Hemorrhage
;
Humans
;
Incidental Findings
;
Male
;
Spinal Cord
;
Tinnitus
;
Veins
7.Knowledge and Attitude Related to Nutritional Supplements and Risk of Doping among National Elite Athletes in Malaysia
Balaravi Chin MQ ; Karppaya H ; Chai WJ ; Samantha Quah LW ; Ramadas A
Malaysian Journal of Nutrition 2017;23(3):409-423
Introduction: Often considered a legitimate strategy to enhance health and performance, the consumption of nutritional supplements (NS) has become a common practice which frequently results in unintentional doping among athletes. Despite a probable association between NS and doping, there are limited studies on this topic in developing countries such as Malaysia. Thus, this study aimed to identify the prevalence of NS usage among national elite athletes and assess their knowledge and attitude regarding its use and doping. Methods: This was a cross-sectional study conducted at the Malaysian National Sports Institute among national elite athletes (n=50) recruited via convenience sampling. The athletes completed a self-administered questionnaire documenting their demographic characteristics, training information, NS consumption, knowledge and attitude related to supplement-doping. The total knowledge and attitude scores were compared according to demography, training information, and NS consumption. Results: The prevalence of NS use among the athletes was 72%. NS usage was significantly associated with training duration (p=0.029), source of nutrition information (p=0.047) and self-exploration on supplements (p=0.045). Supplement-doping knowledge was significantly higher among athletes with tertiary level education (p=0.027), NS users (p=0.044), those obtaining information from nutritionists (p=0.048) and those who had attended nutrition workshops (p<0.001). The attitude score was significantly higher among males (p=0.021), professional athletes (p=0.041), athletes with lower training hours (p=0.010), those obtaining information from nutritionists (p=0.035) and those who had attended nutrition workshops (p=0.005). Conclusion: A demographic- and training-specific education on NS should be provided by qualified nutritionists to reduce the risk of doping amongst athletes.
8.The 28-Day Mortality Prediction in Sepsis Patients Using Static Lactate Concentration and Early Lactate Clearance: An Observational Study
Tan TL ; Noor Asmidar A ; Ong WJ ; Ahmad Fuad Fahmi MN ; Chieng ZL ; Akmal SI
Medicine and Health 2014;9(2):124-133
Sepsis causes high mortality and morbidity. Static lactate concentration and early lactate clearance are cited to be a predictor for sepsis survival. This study examined the clinical utility of static lactate concentration and early lactate clearance within the first six hours of admission in Emergency Department (ED) to predict 28-day mortality rate in sepsis patients. Patients who presented with sepsis, severe sepsis or septic shock and admitted to ED of Universiti Kebangsaan Malaysia Medical Centre were recruited. Blood lactate concentrations were measured upon admission (H0), at 1st hour (H1) and 6th hour (H6), respectively. Either standard treatment of sepsis or early goal directed therapy was initiated according to sepsis severity. A follow-up report was conducted at 28 days via telephone call, e-mail or case notes. Patients were later classified into survivor and non-survivor as final outcome. Static lactate concentration appeared to be significantly higher for non-survivor as compared to the survival group at H0, H1 and H6 (p<0.05). The lactate clearance trend reflects no relationship between early lactate clearance and 28-day mortality. Static lactate
concentration showed a superior predictor for sepsis over early lactate clearance. Although early lactate clearance was unable to prove its ability to predict 28-day mortality, our findings suggest it can be a useful tool to gauge the resuscitation outcome.
Sepsis
9.Patient-Related Barriers to Cancer Pain Management – A Prospective Cross Sectional Study in a Tertiary Hospital
Choy YC ; Wan Nuruddin Shah WJ ; Wong YM ; Boey CY ; Noor Zuhaily MN ; Kumutha T ; Juliana J
Journal of Surgical Academia 2013;3(1):7-12
Effective management of cancer pain is often hampered by patients’ lack of knowledge regarding cancer pain
management and other barriers related to ethnicity and religious beliefs. This cross sectional study was
performed to determine the patient-related barriers to effective cancer pain management. One hundred patients
receiving cancer pain management were studied. Inclusion criteria were: patients over the age of 18 years, able
to communicate, with known diagnosis of cancer, experiencing persistent pain for the past two weeks. A
modified version of the Barriers Questionnaire II (BQ-II) was used and a modified Brief Pain Inventory was
used to assess the pain profile. Barriers such as, patient’s attitude and beliefs, communication skills and fear of
side effects of pain medication were determined, given a score and the summation was recorded as the total
patient related barriers score. Overall, 85% of respondents achieved more than 40% pain relief and the 72 of 100
patients reported low patient related barrier scores of 6 or less. Nevertheless, the main patient related barriers
were: fear of tolerance to opioids (51%), ethnicity (p=0.003) and religious beliefs (p=0.002) which constituted
the major components of the patient-related barriers score. Ethnicity and religious beliefs had significant
influence on patient-related barriers score suggesting the need of further investigation into this area. In order to
achieve a comprehensive view, other barriers to effective cancer pain management such as those related to the
health systems and healthcare providers need to be assessed together.
10.miRNA deregulation in multiple myeloma
Chinese Medical Journal 2011;125(19):3164-3169
Multiple myeloma (MM) is an incurable plasma cell malignancy and is the second most common hematological cancer. It is characterized by complex, recurrent genetic and epigenetic abnormalities. Recent publications have linked miRNAs, a novel class of gene regulators to cancer including MM. miRNAs are about 20 nucleotide, single strand, non-coding RNAs that repress gene expression by mRNA degradation or translational repression. Aberrant miRNA expression profiles have been described in MM, and their functional roles in MM pathogenesis are being increasingly recognized. This review summarizes the current literature on the role of miRNAs in MM and offers perspectives on future research and utilization of miRNAs in MM management.


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