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Fulltext Hyperthermia by near infrared radiation induced immune cells activation and infiltration in breast tumor

Wan Mohd Zawawi WFA, Hibma MH, Salim MI, Jemon K

Sci Rep, 2021 05 13;11(1):10278.
PMID: 33986437 DOI: 10.1038/s41598-021-89740-0

Breast cancer is the most common cancer that causes death in women. Conventional therapies, including surgery and chemotherapy, have different therapeutic effects and are commonly associated with risks and side effects. Near infrared radiation is a technique with few side effects that is used for local hyperthermia, typically as an adjuvant to other cancer therapies. The understanding of the use of near NIR as a monotherapy, and its effects on the immune cells activation and infiltration, are limited. In this study, we investigate the effects of HT treatment using NIR on tumor regression and on the immune cells and molecules in breast tumors. Results from this study demonstrated that local HT by NIR at 43 °C reduced tumor progression and significantly increased the median survival of tumor-bearing mice. Immunohistochemical analysis revealed a significant reduction in cells proliferation in treated tumor, which was accompanied by an abundance of heat shock protein 70 (Hsp70). Increased numbers of activated dendritic cells were observed in the draining lymph nodes of the mice, along with infiltration of T cells, NK cells and B cells into the tumor. In contrast, tumor-infiltrated regulatory T cells were largely diminished from the tumor. In addition, higher IFN-γ and IL-2 secretion was observed in tumor of treated mice. Overall, results from this present study extends the understanding of using local HT by NIR to stimulate a favourable immune response against breast cancer.
Fulltext Antioxidant Activity Evaluation of FlexirubinType Pigment from Chryseobacterium artocarpi CECT 8497 and Related Docking Study

Mogadem A, Almamary MA, Mahat NA, Jemon K, Ahmad WA, Ali I

Molecules, 2021 Feb 12;26(4).
PMID: 33673263 DOI: 10.3390/molecules26040979

The current research is focused on studying the biological efficacy of flexirubin, a pigment extracted from Chryseobacterium artocarpi CECT 8497.Different methods such as DPPH, H2O2, NO•, O2•-, •OH, lipid peroxidation inhibition by FTC and TBA, ferric reducing and ferrous chelating activity were carried out to evaluate the antioxidant activity of flexirubin. Molecular docking was also carried out, seeking the molecular interactions of flexirubin and a standard antioxidant compound with SOD enzyme to figure out the possible flexirubin activity mechanism. The new findings revealed that the highest level of flexirubin exhibited similar antioxidant activity as that of the standard compound according to the H2O2, •OH, O2•-, FTC and TBA methods. On the other hand, flexirubin at the highest level has shown lower antioxidant activity than the positive control according to the DPPH and NO• and even much lower when measured by the FRAP method. Molecular docking showed that the interaction of flexirubin was in the binding cavity of the SOD enzyme and did not affect its metal-binding site. These results revealed that flexirubin has antioxidant properties and can be a useful therapeutic compound in preventing or treating free radical-related diseases.
Fulltext LEP G2548A polymorphism is associated with increased serum leptin and insulin resistance among T2DM Malaysian patients

Ali LA, Jemon K, Latif NA, Bakar SA, Alwi SSS

Biomedicine (Taipei), 2022;12(3):1-11.
PMID: 36381191 DOI: 10.37796/2211-8039.1326

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic syndrome that is rapidly increasing across the world, especially in Malaysia. Leptin plays a vital role in the regulation of metabolism through its effect on peripheral tissues. G2548A polymorphism in the LEP gene promoter has been associated with insulin resistance, leptin, and type 2 diabetes mellitus across different population, but has not been inclusively reported within the Malaysian population.
Objective: Thus, our study aimed to investigate the impact of G2548A polymorphism on serum leptin levels and insulin resistance among Malaysian T2DM patients.
Methods: This case-control study involved 150 T2DM patients and 150 non-diabetic volunteers from ethnic Malays, Chinese and Indians. Genotyping of G2548A polymorphism was carried out using PCR-RFLP. Serum leptin and insulin levels were determined via ELISA. ANOVA and Chi-square tests were used to determine the distribution of genotypes and allelic frequencies based on serum leptin and insulin levels.
Results: Frequency of AA genotype and A allele of G2548A variant were significantly (P < 0.05) higher in T2DM patients of Malay and Indian ethnicities (4%, 35%, and 36%, 57%, respectively) as compared to the control groups (0%, 22%, and 18%, 35%, respectively). Fasting serum leptin levels were significantly (P < 0.001) higher in T2DM patients compared to non-diabetic subjects (166.78 pg/ml, 101.94 pg/ml, respectively). Additionally, elevated serum leptin, insulin levels, and BMI in diabetic patients were found to be associated with the AA genotype of this variant, compared to GG, and GA genotypes (P < 0.05).
Conclusion: Our findings suggest a significant association between G2548A polymorphism among Malaysian T2DM subjects, particularly among Malay and Indian ethnic groups. Moreover, the A allele frequency of the G2548A variant significantly increased the risk of T2DM and is significantly associated with increased serum leptin, insulin levels, and elevated BMI.
Fulltext Synergistic effects of combined cisplatin and Clinacanthus nutans extract on triple negative breast cancer cells

Abu Bakar NFAB, Yeo ZL, Hussin F, Madhavan P, Lim V, Jemon K, et al.

J Taibah Univ Med Sci, 2023 Dec;18(6):1220-1236.
PMID: 37250812 DOI: 10.1016/j.jtumed.2023.04.003

OBJECTIVE: Triple negative breast cancer (TNBC) is the most invasive breast cancer subtype enriched with cancer stem cells. TNBCs do not express estrogen, progesterone, or human epidermal growth factor receptor 2 (HER2) receptors, making them difficult to be targeted by existing chemotherapy treatments. In this study, we attempted to identify the effects of combined cisplatin and Clinacanthus nutans treatment on MDA-MD-231 and MDA-MB-468 breast cancer cells, which represent TNBC subtypes.
METHODS: The phytochemical fingerprint of C. nutans ethanolic leaf extract was evaluated by LC-MS/MS analysis. We investigated the effects of cisplatin (0-15.23 μg/mL), C. nutans (0-50 μg/mL), and a combination of cisplatin (3.05 μg/mL) and C. nutans (0-50 μg/mL), on cell viability, proliferation, apoptosis, invasion, mRNA expression in cancer stem cells (CD49f, KLF4), and differentiation markers (TUBA1A, KRT18) in TNBC cells. In addition, we also studied the interaction between cisplatin and C. nutans.
RESULTS: Derivatives of fatty acids, carboxylic acid ester, and glycosides, were identified as the major bioactive compounds with potential anticancer properties in C. nutans leaf extract. Reductions in cell viability (0-78%) and proliferation (2-77%), as well as a synergistic anticancer effect, were identified in TNBC cells when treated with a combination of cisplatin and C. nutans. Furthermore, apoptotic induction via increased caspase-3/7 activity (MDA-MB-231: 2.73-fold; MDA-MB-468: 3.53-fold), and a reduction in cell invasion capacity to 36%, were detected in TNBC cells when compared to single cisplatin and C. nutans treatments. At the mRNA level, cisplatin and C. nutans differentially regulated specific genes that are responsible for proliferation and differentiation.
CONCLUSION: Our findings demonstrate that the combination of cisplatin and C. nutans represents a potential treatment for TNBC.
Bacterial biofilm growth and perturbation by serine protease from Bacillus sp

Yunus J, Wan Dagang WRZ, Jamaluddin H, Jemon K, Mohamad SE, Jonet MA

Arch Microbiol, 2024 Mar 04;206(4):138.
PMID: 38436775 DOI: 10.1007/s00203-024-03857-0

In nature, bacteria are ubiquitous and can be categorized as beneficial or harmless to humans, but most bacteria have one thing in common which is their ability to produce biofilm. Biofilm is encased within an extracellular polymeric substance (EPS) which provides resistance against antimicrobial agents. Protease enzymes have the potential to degrade or promote the growth of bacterial biofilms. In this study, the effects of a recombinant intracellular serine protease from Bacillus sp. (SPB) on biofilms from Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa were analyzed. SPB was purified using HisTrap HP column and concentrated using Amicon 30 ultra-centrifugal filter. SPB was added with varying enzyme activity and assay incubation period after biofilms were formed in 96-well plates. SPB was observed to have contrasting effects on different bacterial biofilms, where biofilm degradations were observed for both 7-day-old A. baumannii (37.26%) and S. aureus (71.51%) biofilms. Meanwhile, SPB promoted growth of P. aeruginosa biofilm up to 176.32%. Compatibility between protein components in S. aureus biofilm with SPB as well as a simpler membrane structure morphology led to higher biofilm degradation for S. aureus compared to A. baumannii. However, SPB promoted growth of P. aeruginosa biofilm due likely to its degrading protein factors that are responsible for biofilm detachment and dispersion, thus resulting in more multi-layered biofilm formation. Commercial protease Savinase which was used as a comparison showed degradation for all three bacterial biofilms. The results obtained are unique and will expand our understanding on the effects that bacterial proteases have toward biofilms.
Fulltext Alleviation of diabetic nephropathy by zinc oxide nanoparticles in streptozotocin-induced type 1 diabetes in rats

Alomari G, Al-Trad B, Hamdan S, Aljabali AAA, Al Zoubi MS, Al-Batanyeh K, et al.

IET Nanobiotechnol, 2021 Jul;15(5):473-483.
PMID: 34694755 DOI: 10.1049/nbt2.12026

This study examines the effect of nanoparticles with zinc oxides (ZnONPs) on diabetic nephropathy, which is the primary cause of mortality for diabetic patients with end-stage renal disease. Diabetes in adult male rats was induced via intraperitoneal injection of streptozotocin. ZnONPs were intraperitoneally administered to diabetic rats daily for 7 weeks. Diabetes was associated with increases in blood glucose level, 24-h urinary albumin excretion rate, glomerular basement membrane thickness, renal oxidative stress markers, and renal mRNA or protein expression of transforming growth factor-β1, fibronectin, collagen-IV, tumour necrosis factor-α and vascular endothelial growth factor-A. Moreover, the expression of nephrin and podocin, and the mRNA expression of matrix metalloproteinase-9 were decreased in the diabetic group. These changes were not detected in the control group and were significantly prevented by ZnONP treatment. These results provide evidence that ZnONPs ameliorate the renal damage induced in a diabetic rat model of nephropathy through improving renal functionality; inhibiting renal fibrosis, oxidative stress, inflammation and abnormal angiogenesis; and delaying the development of podocyte injury. The present findings may help design the clinical application of ZnONPs for protection against the development of diabetic nephropathy.