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Fulltext Recent Advances, Approaches and Challenges in the Development of Universal Influenza Vaccines

Lim CML, Komarasamy TV, Adnan NAAB, Radhakrishnan AK, Balasubramaniam VRMT

Influenza Other Respir Viruses, 2024 Mar;18(3):e13276.
PMID: 38513364 DOI: 10.1111/irv.13276

Every year, influenza virus infections cause significant morbidity and mortality worldwide. They pose a substantial burden of disease, in terms of not only health but also the economy. Owing to the ability of influenza viruses to continuously evolve, annual seasonal influenza vaccines are necessary as a prophylaxis. However, current influenza vaccines against seasonal strains have limited effectiveness and require yearly reformulation due to the virus undergoing antigenic drift or shift. Vaccine mismatches are common, conferring suboptimal protection against seasonal outbreaks, and the threat of the next pandemic continues to loom. Therefore, there is a great need to develop a universal influenza vaccine (UIV) capable of providing broad and durable protection against all influenza virus strains. In the quest to develop a UIV that would obviate the need for annual vaccination and formulation, a multitude of strategies is currently underway. Promising approaches include targeting the highly conserved epitopes of haemagglutinin (HA), neuraminidase (NA), M2 extracellular domain (M2e) and internal proteins of the influenza virus. The identification and characterization of broadly neutralizing antibodies (bnAbs) targeting conserved regions of the viral HA protein, in particular, have provided important insight into novel vaccine designs and platforms. This review discusses universal vaccine approaches presently under development, with an emphasis on those targeting the highly conserved stalk of the HA protein, recent technological advancements used and the future prospects of a UIV in terms of its advantages, developmental obstacles and potential shortcomings.
Fulltext Colostrum supplementation protects against exercise-induced oxidative stress in skeletal muscle in mice

Appukutty M, Radhakrishnan AK, Ramasamy K, Ramasamy R, Abdul Majeed AB, Noor MI, et al.

BMC Res Notes, 2012;5:649.
PMID: 23173926 DOI: 10.1186/1756-0500-5-649

This study examined the effects of bovine colostrum on exercise -induced modulation of antioxidant parameters in skeletal muscle in mice. Adult male BALB/c mice were randomly divided into four groups (control, colostrum alone, exercise and exercise with colostrum) and each group had three subgroups (day 0, 21 and 42). Colostrum groups of mice were given a daily oral supplement of 50 mg/kg body weight of bovine colostrum and the exercise group of mice were made to exercise on the treadmill for 30 minutes per day. Total antioxidants, lipid hydroperoxides, xanthine oxidase and super oxide dismutase level was assayed from the homogenate of hind limb skeletal muscle.
Fulltext Calculation of free and bioavailable vitamin D and its association with bone mineral density in Malaysian women

Thambiah SC, Wong TH, Das Gupta E, Radhakrishnan AK, Gun SC, Chembalingam G, et al.

Malays J Pathol, 2018 Dec;40(3):287-294.
PMID: 30580359

INTRODUCTION: Low 25-hydroxyvitamin D [25(OH)D] levels have not been consistently associated with bone mineral density (BMD). It has been suggested that calculation of the free/bioavailable 25(OH)D may correlate better with BMD. We examined this hypothesis in a cohort of Malaysian women.

MATERIALS AND METHODS: A cross-sectional study of 77 patients with rheumatoid arthritis (RA) and 29 controls was performed. Serum 25(OH)D was measured using the Roche Cobas E170 immunoassay. Serum vitamin D binding protein (VDBP) was measured using a monoclonal enzyme-linked immunosorbent assay (ELISA). Free/bioavailable 25(OH)D were calculated using both the modified Vermuelen and Bikle formulae.

RESULTS: Since there were no significant differences between RA patients and controls for VDBP and 25(OH)D, the dataset was analysed as a whole. Calculated free 25(OH)D by Vermeulen was strongly correlated with Bikle (r = 1.00, p < 0.001). A significant positive correlation was noted between measured total 25(OH)D with free/bioavailable 25(OH)D (r = 0.607, r = 0.637, respectively, p < 0.001). Median free/bioavailable 25(OH)D values were significantly higher in Chinese compared with Malays and Indians, consistent with their median total 25(OH)D. Similar to total 25(OH)D, the free/bioavailable 25(OH)D did not correlate with BMD.

CONCLUSION: In this first study of a multiethnic female Malaysian population, free/bioavailable 25(OH)D were found to reflect total 25(OH)D, and was not superior to total 25(OH)D in its correlation with BMD. Should they need to be calculated, the Bikle formula is easier to use but only calculates free 25(OH)D. The Vermuelen formula calculates both free/bioavailable 25(OH)D but is more complex to use.
Fulltext Development, Characterization, and Evaluation of α-Mangostin-Loaded Polymeric Nanoparticle Gel for Topical Therapy in Skin Cancer

Md S, Alhakamy NA, Neamatallah T, Alshehri S, Mujtaba MA, Riadi Y, et al.

Gels, 2021 Nov 24;7(4).
PMID: 34842729 DOI: 10.3390/gels7040230

The aim of this study was to prepare and evaluate α-mangostin-loaded polymeric nanoparticle gel (α-MNG-PLGA) formulation to enhance α-mangostin delivery in an epidermal carcinoma. The poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were developed using the emulsion-diffusion-evaporation technique with a 3-level 3-factor Box-Behnken design. The NPs were characterized and evaluated for particle size distribution, zeta potential (mV), drug release, and skin permeation. The formulated PLGA NPs were converted into a preformed carbopol gel base and were further evaluated for texture analysis, the cytotoxic effect of PLGA NPs against B16-F10 melanoma cells, and in vitro radical scavenging activity. The nanoscale particles were spherical, consistent, and average in size (168.06 ± 17.02 nm), with an entrapment efficiency (EE) of 84.26 ± 8.23% and a zeta potential of -25.3 ± 7.1 mV. Their drug release percentages in phosphate-buffered solution (PBS) at pH 7.4 and pH 6.5 were 87.07 ± 6.95% and 89.50 ± 9.50%, respectively. The release of α-MNG from NPs in vitro demonstrated that the biphasic release system, namely, immediate release in the initial phase, was accompanied by sustained drug release. The texture study of the developed α-MNG-PLGA NPs gel revealed its characteristics, including viscosity, hardness, consistency, and cohesiveness. The drug flux from α-MNG-PLGA NPs gel and α-MNG gel was 79.32 ± 7.91 and 16.88 ± 7.18 µg/cm2/h in 24 h, respectively. The confocal study showed that α-MNG-PLGA NPs penetrated up to 230.02 µm deep into the skin layer compared to 15.21 µm by dye solution. MTT assay and radical scavenging potential indicated that α-MNG-PLGA NPs gel had a significant cytotoxic effect and antioxidant effect compared to α-MNG gel (p < 0.05). Thus, using the developed α-MNG-PLGA in treating skin cancer could be a promising approach.
Fulltext Effects of Probiotics on Anxiety, Stress, Mood and Fitness of Badminton Players

Salleh RM, Kuan G, Aziz MNA, Rahim MRA, Rahayu T, Sulaiman S, et al.

Nutrients, 2021 May 24;13(6).
PMID: 34073684 DOI: 10.3390/nu13061783

BACKGROUND: Reports of probiotic consumption on athletes' performance are debatable due to their equivocal results. There is a need for more evidence on the effects of probiotic intake on psychological state and fitness level. Thus, this study determined the effects of daily probiotic consumption on competitive anxiety, perceived stress and mood among university badminton players, besides their fitness like aerobic capacity, strength, speed, leg power and agility.
METHODS: Thirty university badminton players aged from 19 to 22 years old were randomly divided equally into two groups, where the probiotic group (PG; n = 15) received a drink that contained Lactobacillus casei Shirota (3 × 1010 CFU) and placebo group (CG; n = 15) a placebo drink for six weeks. Anxiety, stress and mood levels were determined using the CSAI-2R, PSS and BRUMS questionnaires, respectively. Fitness levels were measured using by subjecting the players to 20-m shuttle runs (aerobic capacity), handgrips (muscular strength), vertical jumps (leg power), 40-m dash (speed) and T-test (agility). The Student's t-test (p < 0.05) was used to determine the differences between PG and CG players.
RESULTS: After six weeks, the anxiety and stress levels of PG players significantly decreased by 16% (p < 0.001) and 20% (p < 0.001), respectively, but there were no significant changes detected in CG players. Supplementation of probiotics also improved aerobic capacity in PG players by 5.9% (p < 0.001) but did not influence the speed, strength, leg power and agility.
CONCLUSIONS: Probiotics supplementation showed improved aerobic capacity and relieve anxiety and stress. However, further studies need to be carried out to determine the mechanisms through which probiotic intake produces these effects.
Nose to brain delivery of rotigotine loaded chitosan nanoparticles in human SH-SY5Y neuroblastoma cells and animal model of Parkinson's disease

Bhattamisra SK, Shak AT, Xi LW, Safian NH, Choudhury H, Lim WM, et al.

Int J Pharm, 2020 Apr 15;579:119148.
PMID: 32084576 DOI: 10.1016/j.ijpharm.2020.119148

Rotigotine, a non-ergoline dopamine agonist, has been shown to be highly effective for the treatment of Parkinson's disease (PD). However, despite its therapeutic potential, its' clinical applications were hindered due to low aqueous solubility, first-pass metabolism and low bioavailability. Therefore, we developed rotigotine-loaded chitosan nanoparticles (RNPs) for nose-to-brain delivery and evaluated its neuronal uptake, antioxidant and neuroprotective effects using cell-based studies. The pharmacological effects of nose-to-brain delivery of the RNPs were also evaluated in an animal model of PD. The average particle size, particle size distribution and entrapment efficiency of the RNPs were found to be satisfactory. Exposure of RNPs for 24 h did not show any cytotoxicity towards SH-SY5Y human neuroblastoma cells. Furthermore, the RNPs caused a decrease in alpha-synuclein (SNCA) and an increase in tyrosine hydroxylase (TH) expression in these cells, suggestion that the exposure alleviated some of the direct neurotoxic effects of 6-OHDA. Behavioral and biochemical testing of RNPs in haloperidol-induced PD rats showed a reversal of catalepsy, akinesia and restoration of swimming ability. A decrease in lactate dehydrogenase (LDH) and an increase in catalase activities were also observed in the brain tissues. The results from the animal model of PD show that intranasally-administered RNPs enhanced brain targeting efficiency and drug bioavailability. Thus, RNPs for nose-to-brain delivery has significant potential to be developed as a treatment approach for PD.
Fulltext Ambroxol Hydrochloride Loaded Gastro-Retentive Nanosuspension Gels Potentiate Anticancer Activity in Lung Cancer (A549) Cells

Md S, Abdullah ST, Alhakamy NA, Bani-Jaber A, Radhakrishnan AK, Karim S, et al.

Gels, 2021 Nov 30;7(4).
PMID: 34940303 DOI: 10.3390/gels7040243

This study aimed to develop gastro-retentive sustained-release ambroxol (ABX) nanosuspensions utilizing ambroxol-kappa-carrageenan (ABX-CRGK) complexation formulations. The complex was characterized by differential scanning calorimetry, powder x-ray diffractometer, and scanning electron microscopy. The prepared co-precipitate complex was used for the development of the sustained-release formulation to overcome the high metabolic and poor solubility problems associated with ABX. Furthermore, the co-precipitate complex was formulated as a suspension in an aqueous floating gel-forming vehicle of sodium alginate with chitosan, which might be beneficial for targeting the stomach as a good absorption site for ABX. The suspension exhibited rapid floating gel behaviour for more than 8 h, thus confirming the gastro-retentive effects. Particle size analysis revealed that the optimum nanosuspension (ABX-NS) had a mean particle size of 332.3 nm. Afterward, the ABX released by the nanoparticles would be distributed to the pulmonary tissue as previously described. Based on extensive pulmonary distribution, the developed nanosuspension-released ABX nanoparticles showed significant cytotoxic enhancement compared to free ABX in A549 lung cancer cells. However, a significant loss of mitochondrial membrane potential (MMP) also occurred. The level of caspase-3 was the highest in the ABX-NS-released particle-treated samples, with a value of 416.6 ± 9.11 pg/mL. Meanwhile, the levels of nuclear factor kappa beta, interleukins 6 and 1 beta, and tumour necrosis alpha (NF-kB, IL-6, IL-1β, and TNF-α, respectively) were lower for ABX-NS compared to free ABX (p < 0.05). In caspase-3, Bax, and p53, levels significantly increased in the presence of ABX-NS compared to free ABX. Overall, ABX-NS produced an enhancement of the anticancer effects of ABX on the A549 cells, and the developed sustained-release gel was successful in providing a gastro-retentive effect.
Fulltext Investigating Genetic and Other Determinants of First-Onset Myocardial Infarction in Malaysia: Protocol for the Malaysian Acute Vascular Events Risk Study

Chowdhury R, Noh MFM, Ismail SR, van Daalen KR, Kamaruddin PSNM, Zulkiply SH, et al.

JMIR Res Protoc, 2022 Feb 10;11(2):e31885.
PMID: 35142634 DOI: 10.2196/31885

BACKGROUND: Although the burden of premature myocardial infarction (MI) is high in Malaysia, direct evidence on the determinants of MI in this multi-ethnic population remains sparse.
OBJECTIVE: The Malaysian Acute Vascular Events Risk (MAVERIK) study is a retrospective case-control study established to investigate the genomic, lipid-related, and other determinants of acute MI in Malaysia. In this paper, we report the study protocol and early results.
METHODS: By June 2019, we had enrolled approximately 2500 patients with their first MI and 2500 controls without cardiovascular disease, who were frequency-matched by age, sex, and ethnicity, from 17 hospitals in Malaysia. For each participant, serum and whole blood have been collected and stored. Clinical, demographic, and behavioral information has been obtained using a 200-item questionnaire.
RESULTS: Tobacco consumption, a history of diabetes, hypertension, markers of visceral adiposity, indicators of lower socioeconomic status, and a family history of coronary disease were more prevalent in cases than in controls. Adjusted (age and sex) logistic regression models for traditional risk factors indicated that current smoking (odds ratio [OR] 4.11, 95% CI 3.56-4.75; P30 kg/m2; OR 1.19, 95% CI 1.05-1.34; P=.009) were associated with MI in age- and sex-adjusted models.
CONCLUSIONS: The MAVERIK study can serve as a useful platform to investigate genetic and other risk factors for MI in an understudied Southeast Asian population. It should help to hasten the discovery of disease-causing pathways and inform regionally appropriate strategies that optimize public health action.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/31885.