Browse publications by year: 2023

Fulltext A Systematic Review and Meta-Analysis of the Impact of Cancer and Its Treatment Protocol on the Success of Orthodontic Treatment

Alam MK, Awawdeh M, Khanagar SB, Aboelmaaty W, Abutayyem H, Alswairki HJ, et al.

Cancers (Basel), 2023 Nov 13;15(22).
PMID: 38001647 DOI: 10.3390/cancers15225387

BACKGROUND: There are several significant gaps in current studies of the relationship between anti-cancer medications and orthodontic care that call for more investigation. As a result, the main goals of this systematic review and meta-analysis were to summarise and assess the information that was available regarding the effect of radiotherapy and anti-cancer medications on the overall successful completion of an orthodontic treatment plan.
METHODS: A standardised data extraction form was devised in accordance with the PRISMA guidelines to conduct a systematic review and meta-analysis, with specific criteria implemented for selecting studies with low to moderate risk of bias.
RESULTS: Five studies involving different methodologies were selected at the conclusion of the search strategy. The statistical analysis revealed an estimated odds ratio (OR) of 0.31 and relative risk (RR) of 0.48, indicating a statistically significant association between the use of radiotherapy and anti-neoplastic drugs and a noticeable reduction in the successful completion of orthodontic treatment. The heterogeneity analysis showed significant heterogeneity among the studies.
CONCLUSIONS: This review emphasises that, although orthodontic therapies can still be beneficial for children receiving chemotherapy, the effectiveness of the therapy may be diminished in older populations. The findings further highlight how crucial it is to take cancer therapies into account when planning and managing orthodontic treatment in order to optimise results and reduce problems.
Fulltext BZD9L1 Differentially Regulates Sirtuins in Liver-Derived Cells by Inducing Reactive Oxygen Species

Lee YT, Tan YJ, Oon CE

Biomedicines, 2023 Nov 15;11(11).
PMID: 38002059 DOI: 10.3390/biomedicines11113059

Growing evidence has highlighted that mitochondrial dysfunction contributes to drug-induced toxicities and leads to drug attrition and post-market withdrawals. The acetylation or deacetylation of mitochondrial proteins can affect mitochondrial functions as the cells adapt to various cellular stresses and other metabolic challenges. SIRTs act as critical deacetylases in modulating mitochondrial function in response to drug toxicity, oxidative stress, reactive oxygen species (ROS), and energy metabolism. We previously showed that a recently characterised SIRT inhibitor (BZD9L1) is non-toxic in rodents in a short-term toxicity evaluation. However, the impact of BZD9L1 on mitochondrial function is unknown. This work aims to determine the effects of BZD9L1 on mitochondrial function in human normal liver and kidney-derived cell lines using the Agilent Seahorse Cell Mito Stress Test to complement our short-term toxicity evaluations in vivo. The Mito Stress assay revealed that BZD9L1 could potentially trigger oxidative stress by inducing ROS, which promotes proton leak and reduces coupling efficiency in liver-derived THLE cells. However, the same was not observed in human kidney-derived HEK293 cells. Interestingly, BZD9L1 had no impact on SIRT3 protein expression in both cell lines but affected SOD2 and its acetylated form at 72 h in THLE cells, indicating that BZD9L1 exerted its effect through SIRT3 activity rather than protein expression. In contrast, BZD9L1 reduced SIRT1 protein expression and impacted the p53 protein differently in both cell lines. Although BZD9L1 did not affect the spare respiratory capacity in vitro, these findings call for further validation of mitochondrial function through assessment of other mitochondrial parameters to evaluate the safety of BZD9L1.
Fulltext Sweet-Tasting Natural Proteins Brazzein and Monellin: Safe Sugar Substitutes for the Food Industry

Novik TS, Koveshnikova EI, Kotlobay AA, Sycheva LP, Kurochkina KG, Averina OA, et al.

Foods, 2023 Nov 08;12(22).
PMID: 38002123 DOI: 10.3390/foods12224065

This article presents the results of a comprehensive toxicity assessment of brazzein and monellin, yeast-produced recombinant sweet-tasting proteins. Excessive sugar consumption is one of the leading dietary and nutritional problems in the world, resulting in health complications such as obesity, high blood pressure, and cardiovascular disease. Although artificial small-molecule sweeteners widely replace sugar in food, their safety and long-term health effects remain debatable. Many sweet-tasting proteins, including thaumatin, miraculin, pentadin, curculin, mabinlin, brazzein, and monellin have been found in tropical plants. These proteins, such as brazzein and monellin, are thousands-fold sweeter than sucrose. Multiple reports have presented preparations of recombinant sweet-tasting proteins. A thorough and comprehensive assessment of their toxicity and safety is necessary to introduce and apply sweet-tasting proteins in the food industry. We experimentally assessed acute, subchronic, and chronic toxicity effects, as well as allergenic and mutagenic properties of recombinant brazzein and monellin. Our study was performed on three mammalian species (mice, rats, and guinea pigs). Assessment of animals' physiological, biochemical, hematological, morphological, and behavioral indices allows us to assert that monellin and brazzein are safe and nontoxic for the mammalian organism, which opens vast opportunities for their application in the food industry as sugar alternatives.
Fulltext Design of Recyclable Carboxylic Metal-Organic Framework/Chitosan Aerogels for Oil Bleaching

Jia XZ, Yao QB, Zhang B, Tan CP, Zeng XA, Huang YY, et al.

Foods, 2023 Nov 16;12(22).
PMID: 38002208 DOI: 10.3390/foods12224151

Novel hierarchical metal-organic framework/chitosan aerogel composites were developed for oil bleaching. UiO-66-COOH-type metal organic frameworks (Zr-MOFs) were synthesized and integrated onto a chitosan matrix with different contents and named MOF-aerogel-1 and MOF-aerogel-2. Due to the compatibility of chitosan, the carboxylic zirconium MOF-aerogels not only maintained the inherent chemical accessibility of UiO-66-COOH, but the unique crystallization and structural characteristics of these MOF nanoparticles were also preserved. Through 3-dimensional reconstructed images, aggregation of the UiO-66-COOH particles was observed in MOF-aerogel-1, while the MOF was homogeneously distributed on the surface of the chitosan lamellae in MOF-aerogel-2. All aerogels, with or without immobilized MOF nanoparticles, were capable of removing carotenoids during oil bleaching. MOF-aerogel-2 showed the most satisfying removal proportions of 26.6%, 36.5%, and 47.2% at 50 °C, 75 °C, and 100 °C, respectively, and its performance was very similar to that of commercial activated clay. The reuse performance of MOF-aerogel-2 was tested, and the results showed its exceptional sustainability for carotenoid removal. These findings suggested the effectiveness of the MOFaerogel for potential utilization in oil bleaching treatments.
Fulltext Recent Progress in Synthesis, POM Analyses and SAR of Coumarin-Hybrids as Potential Anti-HIV Agents-A Mini Review

Suleiman M, Almalki FA, Ben Hadda T, Kawsar SMA, Chander S, Murugesan S, et al.

Pharmaceuticals (Basel), 2023 Oct 31;16(11).
PMID: 38004404 DOI: 10.3390/ph16111538

The human immunodeficiency virus (HIV) is the primary cause of acquired immune deficiency syndrome (AIDS), one of the deadliest pandemic diseases. Various mechanisms and procedures have been pursued to synthesise several anti-HIV agents, but due to the severe side effects and multidrug resistance spawning from the treatment of HIV/AIDS using highly active retroviral therapy (HAART), it has become imperative to design and synthesise novel anti-HIV agents. Literature has shown that natural sources, particularly the plant kingdom, can release important metabolites that have several biological, mechanistic and structural representations similar to chemically synthesised compounds. Certainly, compounds from natural and ethnomedicinal sources have proven to be effective in the management of HIV/AIDS with low toxicity, fewer side effects and affordability. From plants, fungi and bacteria, coumarin can be obtained, which is a secondary metabolite and is well known for its actions in different stages of the HIV replication cycle: protease, integrase and reverse transcriptase (RT) inhibition, cell membrane fusion and viral host attachment. These, among other reasons, are why coumarin moieties will be the basis of a good building block for the development of potent anti-HIV agents. This review aims to outline the synthetic pathways, structure-activity relationship (SAR) and POM analyses of coumarin hybrids with anti-HIV activity, detailing articles published between 2000 and 2023.
Fulltext Evaluating the Potential of Plukenetia volubilis Linneo (Sacha Inchi) in Alleviating Cardiovascular Disease Risk Factors: A Mini Review

Abd Rahman IZ, Nor Hisam NS, Aminuddin A, Hamid AA, Kumar J, Ugusman A

Pharmaceuticals (Basel), 2023 Nov 09;16(11).
PMID: 38004453 DOI: 10.3390/ph16111588

Plukenetia volubilis Linneo or Sacha Inchi (SI), a traditional natural remedy indigenous to Peru and Brazil, has garnered global attention due to its exceptional nutritional composition. Its protective effects against various non-communicable diseases, notably cardiovascular disease (CVD), have become a subject of interest in recent research. This comprehensive review summarizes the existing evidence from 15 relevant articles concerning the impact of SI on common CVD risk factors, including dyslipidemia, obesity, diabetes, and hypertension. The relevant articles were derived from comprehensive searches on PubMed, Scopus, Google Scholar, and Web of Science using predefined criteria and keywords related to the topic. Overall, SI demonstrated positive effects in attenuating dyslipidemia, obesity, diabetes, and hypertension. The multifaceted mechanisms responsible for the protective effects of SI against these CVD risk factors are primarily attributed to its antioxidative and anti-inflammatory properties. While preclinical studies dominate the current scientific literature on SI, there are limited clinical trials to corroborate these findings. Therefore, future well-designed, large-scale randomized clinical trials are highly recommended to establish the efficacy of SI and determine its optimal dosage, potential drug and food interactions, and practical integration into preventive strategies and dietary interventions for the high-risk populations.
Fulltext Quercetin as a Therapeutic Product: Evaluation of Its Pharmacological Action and Clinical Applications-A Review

Mirza MA, Mahmood S, Hilles AR, Ali A, Khan MZ, Zaidi SAA, et al.

Pharmaceuticals (Basel), 2023 Nov 20;16(11).
PMID: 38004496 DOI: 10.3390/ph16111631

Quercetin is the major polyphenolic flavonoid that belongs to the class called flavanols. It is found in many foods, such as green tea, cranberry, apple, onions, asparagus, radish leaves, buckwheat, blueberry, broccoli, and coriander. It occurs in many different forms, but the most abundant quercetin derivatives are glycosides and ethers, namely, Quercetin 3-O-glycoside, Quercetin 3-sulfate, Quercetin 3-glucuronide, and Quercetin 3'-metylether. Quercetin has antioxidant, anti-inflammatory, cardioprotective, antiviral, and antibacterial effects. It is found to be beneficial against cardiovascular diseases, cancer, diabetes, neuro-degenerative diseases, allergy asthma, peptic ulcers, osteoporosis, arthritis, and eye disorders. In pre-clinical and clinical investigations, its impacts on various signaling pathways and molecular targets have demonstrated favorable benefits for the activities mentioned above, and some global clinical trials have been conducted to validate its therapeutic profile. It is also utilized as a nutraceutical due to its pharmacological properties. Although quercetin has several pharmacological benefits, its clinical use is restricted due to its poor water solubility, substantial first-pass metabolism, and consequent low bioavailability. To circumvent this limited bioavailability, a quercetin-based nanoformulation has been considered in recent times as it manifests increased quercetin uptake by the epithelial system and enhances the delivery of quercetin to the target site. This review mainly focuses on pharmacological action, clinical trials, patents, marketed products, and approaches to improving the bioavailability of quercetin with the use of a nanoformulation.
Fulltext Assessing the Protective Role of Epigallocatechin Gallate (EGCG) against Water-Pipe Smoke-Induced Toxicity: A Comparative Study on Gene Expression and Histopathology

Al-Awaida W, Goh KW, Al-Ameer HJ, Gushchina YS, Torshin VI, Severin AE, et al.

Molecules, 2023 Nov 09;28(22).
PMID: 38005223 DOI: 10.3390/molecules28227502

Exposure to water-pipe smoking, whether flavored or unflavored, has been shown to instigate inflammation and oxidative stress in BALB/c mice. This consequently results in alterations in the expression of inflammatory markers and antioxidant genes. This study aimed to scrutinize the impact of Epigallocatechin gallate (EGCG)-a key active component of green tea-on inflammation and oxidative stress in BALB/c mice exposed to water-pipe smoke. The experimental setup included a control group, a flavored water-pipe smoke (FWP) group, an unflavored water-pipe smoke (UFWP) group, and EGCG-treated flavored and unflavored groups (FWP + EGCG and UFWP + EGCG). Expression levels of IL-6, IL1B, TNF-α, CAT, GPXI, MT-I, MT-II, SOD-I, SOD-II, and SOD-III were evaluated in lung, liver, and kidney tissues. Histopathological changes were also assessed. The findings revealed that the EGCG-treated groups manifested a significant decline in the expression of inflammatory markers and antioxidant genes compared to the FWP and UFWP groups. This insinuates that EGCG holds the capacity to alleviate the damaging effects of water-pipe smoke-induced inflammation and oxidative stress. Moreover, enhancements in histopathological features were observed in the EGCG-treated groups, signifying a protective effect against tissue damage induced by water-pipe smoking. These results underscore the potential of EGCG as a protective agent against the adverse effects of water-pipe smoking. By curbing inflammation and oxidative stress, EGCG may aid in the prevention or mitigation of smoking-associated diseases.

MeSH terms: Animals; Antioxidants/metabolism; Antioxidants/pharmacology; Inflammation/drug therapy; Inflammation/metabolism; Superoxide Dismutase/metabolism; Gene Expression; Oxidative Stress; Mice
Fulltext Cytotoxicity Enhancement of α-Mangostin with Folate-Conjugated Chitosan Nanoparticles in MCF-7 Breast Cancer Cells

Herdiana Y, Wathoni N, Shamsuddin S, Muchtaridi M

Molecules, 2023 Nov 14;28(22).
PMID: 38005306 DOI: 10.3390/molecules28227585

α-mangostin (AM) is a promising natural anticancer agent that can be used in cancer research. However, its effectiveness can be limited by poor solubility and bioavailability. To address this issue, chitosan-based nanoparticles (CSNPs) have been investigated as a potential delivery system to enhance the cytotoxicity to cancer cells and improve selectivity against normal cells. In this study, we developed folate-conjugated chitosan nanoparticles (F-CS-NPs) using a carbodiimide-based conjugation method to attach folate to chitosan (CS), which have different molecular weights. The NPs were crosslinked using tripolyphosphate (TPP) via ionic gelation. To characterize the F-CS-NPs, we utilized various analytical techniques, including transmission electron microscopy (TEM) to evaluate the particle size and morphology, Fourier-transform infrared spectroscopy (FTIR) to confirm the presence of functional groups, and ultraviolet-visible spectroscopy (UV-Vis) to measure the absorption spectrum and confirm the presence of folate. The particle size of AM-F-CS-NPs ranged from 180 nm to 250 nm, with many having favorable charges ranging from +40.33 ± 3.4 to 10.69 ± 1.3 mV. All NPs exhibited the same spherical morphology. The use of F-CS-NPs increased drug release, followed by a sustained release pattern. We evaluated the cytotoxicity of AM, AM-F-CS-HMW, and AM-F-CS-LMW NPs against MCF-7 cells and found IC50 values of 8.47 ± 0.49, 5.3 ± 0.01, and 4.70 ± 0.11 µg/mL, respectively. These results confirm the improved cytotoxicity of AM in MCF-7 cells when delivered via F-CS-NPs. Overall, our in vitro study demonstrated that the properties of F-CS-NPs greatly influence the cytotoxicity of AM in MCF-7 breast cancer cells (significantly different (p < 0.05)). The use of F-CS-NPs as a drug-delivery system for AM may have the potential to develop novel therapies for breast cancer.

MeSH terms: Drug Carriers/chemistry; Female; Folic Acid; Humans; Particle Size; MCF-7 Cells
Fulltext Synthesis and Structural Characterization of Novel Dimers of Dipyridothiazine as Promising Antiproliferative Agents

Martula E, Morak-Młodawska B, Jeleń M, Okechukwu PN, Balachandran A, Tehirunavukarasu P, et al.

Molecules, 2023 Nov 19;28(22).
PMID: 38005384 DOI: 10.3390/molecules28227662

Many new isomeric dipyridothiazine dimers have been presented as molecules with anticancer potential. These compounds were obtained in efficient syntheses of 1,6-, 1,8-, 2,7- and 3,6-diazaphenothiazines with selected alkylaromatic linkers. The structures of these compounds has been proven with two-dimensional spectroscopic techniques (COSY, NOESY, HSQC and HMBC) and high-resolution mass spectrometry (HRMS). In silico analyses of probable molecular targets were performed using the Way2Drug server. All new dimers were tested for anticancer activity against breast cancer line MCF7 and colon cancer line SW480. Cytotoxicity was assessed on normal L6 muscle cells. The tested dimers had high anticancer potential expressed as IC50 and the selectivity index SI. The most active derivative, 4c, showed an IC50 activity of less than 1 µM and an SI selectivity index higher than 100. Moreover, the compounds were characterized by low toxicity towards normal cells, simultaneously indicating a high cytostatic potential.

MeSH terms: Drug Screening Assays, Antitumor; Magnetic Resonance Spectroscopy; Structure-Activity Relationship; Molecular Structure; Cell Proliferation
Fulltext Personalized Federated Learning Algorithm with Adaptive Clustering for Non-IID IoT Data Incorporating Multi-Task Learning and Neural Network Model Characteristics

Hsu HY, Keoy KH, Chen JR, Chao HC, Lai CF

Sensors (Basel), 2023 Nov 07;23(22).
PMID: 38005404 DOI: 10.3390/s23229016

The proliferation of IoT devices has led to an unprecedented integration of machine learning techniques, raising concerns about data privacy. To address these concerns, federated learning has been introduced. However, practical implementations face challenges, including communication costs, data and device heterogeneity, and privacy security. This paper proposes an innovative approach within the context of federated learning, introducing a personalized joint learning algorithm for Non-IID IoT data. This algorithm incorporates multi-task learning principles and leverages neural network model characteristics. To overcome data heterogeneity, we present a novel clustering algorithm designed specifically for federated learning. Unlike conventional methods that require a predetermined number of clusters, our approach utilizes automatic clustering, eliminating the need for fixed cluster specifications. Extensive experimentation demonstrates the exceptional performance of the proposed algorithm, particularly in scenarios with specific client distributions. By significantly improving the accuracy of trained models, our approach not only addresses data heterogeneity but also strengthens privacy preservation in federated learning. In conclusion, we offer a robust solution to the practical challenges of federated learning in IoT environments. By combining personalized joint learning, automatic clustering, and neural network model characteristics, we facilitate more effective and privacy-conscious machine learning in Non-IID IoT data settings.
Fulltext EnViTSA: Ensemble of Vision Transformer with SpecAugment for Acoustic Event Classification

Lim KM, Lee CP, Lee ZY, Alqahtani A

Sensors (Basel), 2023 Nov 10;23(22).
PMID: 38005472 DOI: 10.3390/s23229084

Recent successes in deep learning have inspired researchers to apply deep neural networks to Acoustic Event Classification (AEC). While deep learning methods can train effective AEC models, they are susceptible to overfitting due to the models' high complexity. In this paper, we introduce EnViTSA, an innovative approach that tackles key challenges in AEC. EnViTSA combines an ensemble of Vision Transformers with SpecAugment, a novel data augmentation technique, to significantly enhance AEC performance. Raw acoustic signals are transformed into Log Mel-spectrograms using Short-Time Fourier Transform, resulting in a fixed-size spectrogram representation. To address data scarcity and overfitting issues, we employ SpecAugment to generate additional training samples through time masking and frequency masking. The core of EnViTSA resides in its ensemble of pre-trained Vision Transformers, harnessing the unique strengths of the Vision Transformer architecture. This ensemble approach not only reduces inductive biases but also effectively mitigates overfitting. In this study, we evaluate the EnViTSA method on three benchmark datasets: ESC-10, ESC-50, and UrbanSound8K. The experimental results underscore the efficacy of our approach, achieving impressive accuracy scores of 93.50%, 85.85%, and 83.20% on ESC-10, ESC-50, and UrbanSound8K, respectively. EnViTSA represents a substantial advancement in AEC, demonstrating the potential of Vision Transformers and SpecAugment in the acoustic domain.
Fulltext Acinetobacter baumannii in suspected bacterial infections: Association between multidrug resistance, virulence genes, & biofilm production

Gautam D, Dolma KG, Khandelwal B, Goyal RK, Mitsuwan W, Pereira MLG, et al.

Indian J Med Res, 2023 Oct 01;158(4):439-446.
PMID: 38006347 DOI: 10.4103/ijmr.ijmr_3470_21

BACKGROUND OBJECTIVES: Acinetobacter baumannii has emerged as a nosocomial pathogen with a tendency of high antibiotic resistance and biofilm production. This study aimed to determine the occurrence of A. baumannii from different clinical specimens of suspected bacterial infections and furthermore to see the association of biofilm production with multidrug resistance and expression of virulence factor genes in A. baumannii.
METHODS: A. baumannii was confirmed in clinical specimens by the detection of the blaOXA-51-like gene. Biofilm production was tested by microtitre plate assay and virulence genes were detected by real-time PCR.
RESULTS: A. baumannii was isolated from a total of 307 clinical specimens. The isolate which showed the highest number of A. baumannii was an endotracheal tube specimen (44.95%), then sputum (19.54%), followed by pus (17.26%), urine (7.49%) and blood (5.86%), and <2 per cent from body fluids, catheter-tips and urogenital specimens. A resistance rate of 70-81.43 per cent against all antibiotics tested, except colistin and tigecycline, was noted, and 242 (78.82%) isolates were multidrug-resistant (MDR). Biofilm was detected in 205 (66.78%) with a distribution of 54.1 per cent weak, 10.42 per cent medium and 2.28 per cent strong biofilms. 71.07 per cent of MDR isolates produce biofilm (P<0.05). Amongst virulence factor genes, 281 (91.53%) outer membrane protein A (OmpA) and 98 (31.92%) biofilm-associated protein (Bap) were detected. Amongst 100 carbapenem-resistant A. baumannii, the blaOXA-23-like gene was predominant (96%), the blaOXA-58-like gene (6%) and none harboured the blaOXA-24-like gene. The metallo-β-lactamase genes blaIMP-1 (4%) and blaVIM-1(8%) were detected, and 76 per cent showed the insertion sequence ISAba1.
INTERPRETATION CONCLUSIONS: The majority of isolates studied were from lower respiratory tract specimens. The high MDR rate and its positive association with biofilm formation indicate the nosocomial distribution of A. baumannii. The biofilm formation and the presence of Bap were not interrelated, indicating that biofilm formation was not regulated by a single factor. The MDR rate and the presence of OmpA and Bap showed a positive association (P<0.05). The isolates co-harbouring different carbapenem resistance genes were the predominant biofilm producers, which will seriously limit the therapeutic options suggesting the need for strict antimicrobial stewardship and molecular surveillance in hospitals.

MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/therapeutic use; Bacterial Infections*; Bacterial Proteins/genetics; beta-Lactamases/genetics; Humans; Microbial Sensitivity Tests; Virulence/genetics; Carbapenems/pharmacology; Carbapenems/therapeutic use; Biofilms; Drug Resistance, Multiple, Bacterial/genetics; Virulence Factors/genetics; Acinetobacter baumannii*
Anticancer effect of aromatic isoniazid derivatives in human gastric adenocarcinoma cells

Barathan M, Shivashekaregowda NKH, Hoong SM, Vellasamy KM, Vadivelu J

Toxicol Appl Pharmacol, 2023 Dec 15;481:116767.
PMID: 38007073 DOI: 10.1016/j.taap.2023.116767

Current treatments for stomach cancer are often effective in curing cancer. However, these treatments can also have significant side effects, and they may not be effective in all cases. Hence synthetic compounds exhibit promise as potential agents for cancer treatment. In a previous study, we identified (E)-N'- (2,3,4-trihydroxybenzylidene) isonicotinohydrazide (ITHB4) as a novel antimycobacterial derivative of isoniazid with cytotoxic effects on the MCF-7 breast cancer cell line. This led us to investigate the potential anti-cancer properties of ITHB4 against adenocarcinoma gastric (AGS) cell line. The cytotoxic effect of ITHB4 has been determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and further confirmed for anticancer properties by means of apoptosis, reactive oxygen species (ROS), nuclear fragmentation, lactate dehydrogenase (LDH), caspases, cytokines and morphological including phenotypic changes of cells assay. The ITHB4 demonstrated a lower IC50 in inhibiting growth of AGS cells at 24 h compared to 48 and 72 h. ITHB4 has also shown no toxicity human immune cells. Treatment of ITHB4 against AGS for 24 h eventually lead to formation of early apoptotic AGS cells, reduced mitochondrial membrane potential, nuclear condensation, and nuclear fragmentation lastly increased in ROS levels together with the release of LDH, and secretion of caspases. The altered cytokine profile in ITHB4 treated AGS hints at the possibility that ITHB4 may possess anti-tumor and anti-inflammatory properties. Our results in this study demonstrate that ITHB4 has almost similar chemotherapeutic properties against gastric adenocarcinoma cells compared to breast cancer cell. This is suggesting that the anticancer capabilities of this compound should be in vivo and clinically assessed.

MeSH terms: Female; Humans; Isoniazid/pharmacology; Apoptosis; Reactive Oxygen Species/metabolism; Caspases; Cell Line, Tumor; Cell Proliferation
Violence and trauma encountered by Rohingya women fleeing to Malaysia: a qualitative study

Rajaratnam S, Azman A

Arch Womens Ment Health, 2023 Nov 25.
PMID: 38006427 DOI: 10.1007/s00737-023-01402-4

Rohingya women are doubly marginalized owing to their ethnicity and gender. Therefore, this study aims to describe the unique experiences of violence faced by Rohingya women who fled Myanmar and Bangladesh to seek asylum in Malaysia before, during, and after their transit. Primary data were collected from 33 participants comprising Rohingya women refugees and asylum seekers, medical social workers, medical officials, volunteer workers/activists, refugee organization officers, and a mental health care provider. Thematic analysis was used to identify the patterns in and relationships between the concepts in the collected data. Rohingya women were exposed to various forms of violence and trauma by various groups of men, including those from their own community, throughout their journey to and in Malaysia. The lack of recognition of refugees and asylum seekers in Malaysia prevents them from having mainstream or legal access to jobs, education, and healthcare, and this predicament compounds their suffering from violence, especially for women and girls. Rohingya women and girls in Malaysia need better access to healthcare, resources, and support to identify and address violence, which has a significant impact on their health.
Fulltext Right Parapharyngeal Cavernous Hemangioma, A Rare Entity: Case Report and Literature Review

Rose SE, Toong LY, Ghauth S, Ong DB

Ear Nose Throat J, 2023 Nov 24.
PMID: 37997797 DOI: 10.1177/01455613231212597

Cavernous hemangioma is a noncancerous vascular growth that arises from different parts of the head and neck region. However, parapharyngeal space contributes a very small percentage for its occurrence. We present a case of right parapharyngeal cavernous hemangioma, a very rare clinical presentation. This is a 57-year-old female presented with throat discomfort for 3 months. Examination finding showed a soft, diffuse, and non-pulsating mass over the right upper jugulodigastric region. A contrasted computed topographic scan revealed multiple calcifications in right parapharyngeal space. T2-weighted magnetic resonance imaging showed right parapharyngeal space mass with high signal and multiple phleboliths and dynamic angiogram unremarkable. Surgical resection done via transcervical approach and histopathological report revealed cavernous hemangioma with calcified thrombi. In conclusion, surgical intervention is the mainstay treatment and transcervical approach which is adopted in this case is the commonest approach used in surgical resection of cavernous hemangioma.
Fulltext Optimizing HCV Disease Prediction in Egypt: The hyOPTGB Framework

Elshewey AM, Shams MY, Tawfeek SM, Alharbi AH, Ibrahim A, Abdelhamid AA, et al.

Diagnostics (Basel), 2023 Nov 13;13(22).
PMID: 37998575 DOI: 10.3390/diagnostics13223439

The paper focuses on the hepatitis C virus (HCV) infection in Egypt, which has one of the highest rates of HCV in the world. The high prevalence is linked to several factors, including the use of injection drugs, poor sterilization practices in medical facilities, and low public awareness. This paper introduces a hyOPTGB model, which employs an optimized gradient boosting (GB) classifier to predict HCV disease in Egypt. The model's accuracy is enhanced by optimizing hyperparameters with the OPTUNA framework. Min-Max normalization is used as a preprocessing step for scaling the dataset values and using the forward selection (FS) wrapped method to identify essential features. The dataset used in the study contains 1385 instances and 29 features and is available at the UCI machine learning repository. The authors compare the performance of five machine learning models, including decision tree (DT), support vector machine (SVM), dummy classifier (DC), ridge classifier (RC), and bagging classifier (BC), with the hyOPTGB model. The system's efficacy is assessed using various metrics, including accuracy, recall, precision, and F1-score. The hyOPTGB model outperformed the other machine learning models, achieving a 95.3% accuracy rate. The authors also compared the hyOPTGB model against other models proposed by authors who used the same dataset.
Fulltext Cloning, Expression and Functional Characterization of a Novel α-Humulene Synthase, Responsible for the Formation of Sesquiterpene in Agarwood Originating from Aquilaria malaccensis

Sundaraj Y, Abdullah H, Nezhad NG, Rasib AAA, Othman R, Rodrigues KF, et al.

Curr Issues Mol Biol, 2023 Nov 10;45(11):8989-9002.
PMID: 37998741 DOI: 10.3390/cimb45110564

This study describes the cloning, expression and functional characterization of α-humulene synthase, responsible for the formation of the key aromatic compound α-humulene in agarwood originating from Aquilaria malaccensis. The partial sesquiterpene synthase gene from the transcriptome data of A. malaccensis was utilized for full-length gene isolation via a 3' RACE PCR. The complete gene, denoted as AmDG2, has an open reading frame (ORF) of 1671 bp and encodes for a polypeptide of 556 amino acids. In silico analysis of the protein highlighted several conserved motifs typically found in terpene synthases such as Asp-rich substrate binding (DDxxD), metal-binding residues (NSE/DTE), and cytoplasmic ER retention (RxR) motifs at their respective sites. The AmDG2 was successfully expressed in the E. coli:pET-28a(+) expression vector whereby an expected band of about 64 kDa in size was detected in the SDS-PAGE gel. In vitro enzyme assay using substrate farnesyl pyrophosphate (FPP) revealed that AmDG2 gave rise to two sesquiterpenes: α-humulene (major) and β-caryophyllene (minor), affirming its identity as α-humulene synthase. On the other hand, protein modeling performed using AlphaFold2 suggested that AmDG2 consists entirely of α-helices with short connecting loops and turns. Meanwhile, molecular docking via AutoDock Vina (Version 1.5.7) predicted that Asp307 and Asp311 act as catalytic residues in the α-humulene synthase. To our knowledge, this is the first comprehensive report on the cloning, expression and functional characterization of α-humulene synthase from agarwood originating from A. malaccensis species. These findings reveal a deeper understanding of the structure and functional properties of the α-humulene synthase and could be utilized for metabolic engineering work in the future.
Fulltext The Microbiome of Peri-Implantitis: A Systematic Review of Next-Generation Sequencing Studies

Chun Giok K, Menon RK

Antibiotics (Basel), 2023 Nov 09;12(11).
PMID: 37998812 DOI: 10.3390/antibiotics12111610

(1) Introduction: Current evidence shows that mechanical debridement augmented with systemic and topical antibiotics may be beneficial for the treatment of peri-implantitis. The microbial profile of peri-implantitis plays a key role in identifying the most suitable antibiotics to be used for the treatment and prevention of peri-implantitis. This systematic review aimed to summarize and critically analyze the methodology and findings of studies which have utilized sequencing techniques to elucidate the microbial profiles of peri-implantitis. (2) Results: Fusobacterium, Treponema, and Porphyromonas sp. are associated with peri-implantitis. Veillonella sp. are associated with healthy implant sites and exhibit a reduced prevalence in deeper pockets and with greater severity of disease progression. Streptococcus sp. have been identified both in diseased and healthy sites. Neisseria sp. have been associated with healthy implants and negatively correlate with the probing depth. Methanogens and AAGPRs were also detected in peri-implantitis sites. (3) Methods: The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023459266). The PRISMA criteria were used to select articles retrieved from a systematic search of the Scopus, Cochrane, and Medline databases until 1 August 2023. Title and abstract screening was followed by a full-text review of the included articles. Thirty-two articles were included in the final qualitative analysis. (4) Conclusions: A distinct microbial profile could not be identified from studies employing sequencing techniques to identify the microbiome. Further studies are needed with more standardization to allow a comparison of findings. A universal clinical parameter for the diagnosis of peri-implantitis should be implemented in all future studies to minimize confounding factors. The subject pool should also be more diverse and larger to compensate for individual differences, and perhaps a distinct microbial profile can be seen with a larger sample size.
Fulltext Comparative Study on the Antimicrobial Activities and Metabolic Profiles of Five Usnea Species from the Philippines

Dela Cruz TEE, Timbreza LP, Sangvichien E, Notarte KIR, Santiago KAA

J Fungi (Basel), 2023 Nov 17;9(11).
PMID: 37998922 DOI: 10.3390/jof9111117

The rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics. Hence, there is a need to search for new sources of antibiotics that either exhibit novel structures or express a new mechanism of action. The lichen Usnea, with its wide range of unique, biologically potent secondary metabolites, may solve this problem. In this study, Usnea species were collected in the Northern Philippines, identified through combined morphological and biochemical characterization, and tested for antimicrobial activities against the multidrug-resistant ESKAPE pathogens, i.e., Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae, two standard antibiotic-sensitive test bacteria, and a yeast. A total of 46 lichen specimens were collected and later identified as Usnea baileyi (10), U. diffracta (10), U. glabrata (12), U. longissima (4), and U. rubicunda (10). The results show that the crude extracts of the Usnea species exhibited promising in vitro inhibitory activities against standard antibiotic-sensitive (E. faecalis ATCC 29212) and multidrug-resistant (methicillin-resistant S. aureus and E. faecalis) Gram-positive bacteria. Additionally, lichen compounds of representative specimens per species were identified and profiled using thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). The detection of lichen acids (LA) via HPLC showed the presence of 24 peaks of lichen acids. TLC-bioautography identified the bioactive lichen acids as alectronic acid, connorstictic acid, consalazinic acid, diffractaic acid, echinocarpic acid, erythrin acid, galbinic acid, hypoconstictic acid, hyposalazinic acid, hypostictic acid, lobaric acid, menegazzaic acid, micareic acid, pannarin, salazinic acid, stictic acid, and usnic acid. Our study highlighted the wide spectrum of opportunities for using lichens for the discovery of potential antimicrobial agents.

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