Potential Chemopreventive Role of Pterostilbene in Its Modulation of the Apoptosis Pathway.

Cancer incidence keeps increasing every year around the world and is one of the leading causes of death worldwide. Cancer has imposed a major burden on the human population, including the deterioration of physical and mental health as well as economic or financial loss among cancer patients. Conventional cancer treatments including chemotherapy, surgery, and radiotherapy have improved the mortality rate. However, conventional treatments have many challenges; for example, drug resistance, side effects, and cancer recurrence. Chemoprevention is one of the promising interventions to reduce the burden of cancer together with cancer treatments and early detection. Pterostilbene is a natural chemopreventive compound with various pharmacological properties such as anti-oxidant, anti-proliferative, and anti-inflammatory properties. Moreover, pterostilbene, due to its potential chemopreventive effect on inducing apoptosis in eliminating the mutated cells or preventing the progression of premalignant cells to cancerous cells, should be explored as a chemopreventive agent. Hence, in the review, we discuss the role of pterostilbene as a chemopreventive agent against various types of cancer via its modulation of the apoptosis pathway at the molecular levels.

Burkholderia pseudomallei pathogenesis and survival in different niches.

Burkholderia pseudomallei (Bp) is the causative agent of melioidosis, a disease of the tropics with high clinical mortality rates. To date, no vaccines are approved for melioidosis and current treatment relies on antibiotics. Conversely, common misdiagnosis and high pathogenicity of Bp hamper efforts to fight melioidosis. This bacterium can be isolated from a wide range of niches such as waterlogged fields, stagnant water bodies, salt water bodies and from human and animal clinical specimens. Although extensive studies have been undertaken to elucidate pathogenesis mechanisms of Bp, little is known about how a harmless soil bacterium adapts to different environmental conditions, in particular, the shift to a human host to become a highly virulent pathogen. The bacterium has a large genome encoding an armory of factors that assist the pathogen in surviving under stressful conditions and assuming its role as a deadly intracellular pathogen. This review presents an overview of what is currently known about how the pathogen adapts to different environments. With in-depth understanding of Bp adaptation and survival, more effective therapies for melioidosis can be developed by targeting related genes or proteins that play a major role in the bacteria's survival.

EFFECT OF AGE AND GENDER ON FASTING AND FOOD-STIMULATED LEVELS OF CALCITONIN, PARATHYROID, AND GASTRIN HORMONES IN HEALTHY ADULTS.

Objective: To investigate the effect of age and gender on basal and food-stimulated serum calcitonin (CT), parathyroid hormone (PTH), and gastrin levels among healthy adults. Methods: Ninety-six healthy adults (76 men and 20 women) aged between 21 and 43 years were recruited. Serum CT, PTH, and gastrin levels were measured after a 9-hour overnight fast, and 1 and 3 hours postprandially. Results: PTH levels decreased early and increased late after feeding. This change was significant in men but not in women. CT levels increased in response to food intake in men but not in women. Gastrin levels were significantly increased after feeding in both men and women. Mean basal and food stimulated CT, PTH, and gastrin levels did not significantly differ between genders. Fasting and post-prandial PTH levels were higher while gastrin levels were lower in older subjects (>30 years old) compared to younger subjects (≤30 years old). Fasting and postprandial CT levels were not significantly different between age groups. Conclusion: Age had a significant effect on fasting and food-stimulated PTH and gastrin hormone levels. The effect of age on PTH levels was independent of baseline vitamin D levels. Men showed significant changes in CT and PTH levels in response to feeding compared to women, although the mean hormone levels were not significantly different between men and women. Abbreviations: CT = calcitonin; MTC = medullary thyroid carcinoma; PTH = parathyroid hormone; SD = standard deviation.

Total Protein Concentration and Tumor Necrosis Factor α in Tears of Nonproliferative Diabetic Retinopathy.

SIGNIFICANCE: Total protein concentration (TPC) and tumor necrosis factor α (TNF-α) concentration in tears are correlated with severity of retinopathy. However, minimal data are available in the literature for investigating tear TPC and TNF-α concentrations in Asian individuals with different severity of nonproliferative diabetic retinopathy (NPDR). PURPOSE: This study evaluated differences of TPC and TNF-α concentrations in tears at different severity of NPDR among participants with diabetes in comparison with normal participants. METHODS: A total of 75 participants were categorized based on Early Treatment for Diabetic Retinopathy Study scale, with 15 participants representing each group, namely, normal, diabetes without retinopathy, mild NPDR, moderate NPDR, and severe NPDR. All participants were screened using McMonnies questionnaire. Refraction was conducted subjectively. Visual acuity was measured using a LogMAR chart. Twenty-five microliters of basal tears was collected using glass capillary tubes. Total protein concentration and TNF-α concentrations were determined using Bradford assay and enzyme-linked immunosorbent assay, respectively. RESULTS: Mean ± SD age of participants (n = 75) was 57.88 ± 4.71 years, and participants scored equally in McMonnies questionnaire (P = .90). Mean visual acuity was significantly different in severe NPDR (P = .003). Mean tear TPC was significantly lower, and mean tear TNF-α concentration was significantly higher in moderate and severe NPDR (P < .001). Mean ± SD tear TPC and TNF-α concentrations for normal were 7.10 ± 1.53 and 1.39 ± 0.24 pg/mL; for diabetes without retinopathy, 6.37 ± 1.65 and 1.53 ± 0.27 pg/mL; for mild NPDR, 6.32 ± 2.05 and 1.60 ± 0.21 pg/mL; for moderate NPDR, 3.88 ± 1.38 and 1.99 ± 0.05 pg/mL; and for severe NPDR, 3.64 ± 1.26 and 2.21 ± 0.04 pg/mL, respectively. Tear TPC and TNF-α concentrations were significantly correlated (r = -0.50, P < .0001). Visual acuity was significantly correlated with tear TPC (r = -0.236, P = .04) and TNF-α concentrations (r = 0.432, P < .0001). CONCLUSIONS: This cross-sectional study identified differences in tear TPC and TNF-α concentrations with increasing severity of NPDR.

Bursal transcriptome profiling of different inbred chicken lines reveals key differentially expressed genes at 3 days post-infection with very virulent infectious bursal disease virus.

Infectious bursal disease is a highly contagious disease in the poultry industry and causes immunosuppression in chickens. Genome-wide regulations of immune response genes of inbred chickens with different genetic backgrounds, following very virulent infectious bursal disease virus (vvIBDV) infection are poorly characterized. Therefore, this study aims to analyse the bursal tissue transcriptome of six inbred chicken lines 6, 7, 15, N, O and P following infection with vvIBDV strain UK661 using strand-specific next-generation sequencing, by highlighting important genes and pathways involved in the infected chicken during peak infection at 3 days post-infection. All infected chickens succumbed to the infection without major variations among the different lines. However, based on the viral loads and bursal lesion scoring, lines P and 6 can be considered as the most susceptible lines, while lines 15 and N were regarded as the least affected lines. Transcriptome profiling of the bursa identified 4588 genes to be differentially expressed, with 2985 upregulated and 1642 downregulated genes, in which these genes were commonly or uniquely detected in all or several infected lines. Genes that were upregulated are primarily pro-inflammatory cytokines, chemokines and IFN-related. Various genes that are associated with B-cell functions and genes related to apoptosis were downregulated, together with the genes involved in p53 signalling. In conclusion, bursal transcriptome profiles of different inbred lines showed differential expressions of pro-inflammatory cytokines and chemokines, Th1 cytokines, JAK-STAT signalling genes, MAPK signalling genes, and their related pathways following vvIBDV infection.

Bactericidal Effect of Pterostilbene Alone and in Combination with Gentamicin against Human Pathogenic Bacteria.

The antibacterial activity of pterostilbene in combination with gentamicin against six strains of Gram-positive and Gram-negative bacteria were investigated. The minimum inhibitory concentration and minimum bactericidal concentration of pterostilbene were determined using microdilution technique whereas the synergistic antibacterial activities of pterostilbene in combination with gentamicin were assessed using checkerboard assay and time-kill kinetic study. Results of the present study showed that the combination effects of pterostilbene with gentamicin were synergistic (FIC index < 0.5) against three susceptible bacteria strains: Staphylococcus aureus ATCC 25923, Escherichia coli O157 and Pseudomonas aeruginosa 15442. However, the time-kill study showed that the interaction was indifference which did not significantly differ from the gentamicin treatment. Furthermore, time-kill study showed that the growth of the tested bacteria was completely attenuated with 2 to 8 h treatment with 0.5 × MIC of pterostilbene and gentamicin. The identified combinations could be of effective therapeutic value against bacterial infections. These findings have potential implications in delaying the development of bacterial resistance as the antibacterial effect was achieved with the lower concentrations of antibacterial agents.

De novo transcriptome analyses of host-fungal interactions in oil palm (Elaeis guineensis Jacq.).

BACKGROUND: Basal stem rot (BSR) is a fungal disease in oil palm (Elaeis guineensis Jacq.) which is caused by hemibiotrophic white rot fungi belonging to the Ganoderma genus. Molecular responses of oil palm to these pathogens are not well known although this information is crucial to strategize effective measures to eradicate BSR. In order to elucidate the molecular interactions between oil palm and G. boninense and its biocontrol fungus Trichoderma harzianum, we compared the root transcriptomes of untreated oil palm seedlings with those inoculated with G. boninense and T. harzianum, respectively. RESULTS: Differential gene expression analyses revealed that jasmonate (JA) and salicylate (SA) may act in an antagonistic manner in affecting the hormone biosynthesis, signaling, and downstream defense responses in G. boninense-treated oil palm roots. In addition, G. boninense may compete with the host to control disease symptom through the transcriptional regulation of ethylene (ET) biosynthesis, reactive oxygen species (ROS) production and scavenging. The strengthening of host cell walls and production of pathogenesis-related proteins as well as antifungal secondary metabolites in host plants, are among the important defense mechanisms deployed by oil palm against G. boninense. Meanwhile, endophytic T. harzianum was shown to improve the of nutrition status and nutrient transportation in host plants. CONCLUSION: The findings of this analysis have enhanced our understanding on the molecular interactions of G. boninense and oil palm, and also the biocontrol mechanisms involving T. harzianum, thus contributing to future formulations of better strategies for prevention and treatment of BSR.

Global transcriptional analysis of Burkholderia pseudomallei high and low biofilm producers reveals insights into biofilm production and virulence.

BACKGROUND: Chronic bacterial infections occur as a result of the infecting pathogen's ability to live within a biofilm, hence escaping the detrimental effects of antibiotics and the immune defense system. Burkholderia pseudomallei, a gram-negative facultative pathogen, is distinctive in its ability to survive within phagocytic and non-phagocytic cells, to persist in vivo for many years and subsequently leading to relapse as well as the development of chronic disease. The capacity to persist has been attributed to the pathogen's ability to form biofilm. However, the underlying biology of B. pseudomallei biofilm development remains unresolved. RESULTS: We utilised RNA-Sequencing to identify genes that contribute to B. pseudomallei biofilm phenotype. Transcriptome analysis of a high and low biofilm producer identified 563 differentially regulated genes, implying that expression of ~9.5% of the total B. pseudomallei gene content was altered during biofilm formation. Genes involved in surface-associated motility, surface composition and cell wall biogenesis were over-expressed and probably play a role in the initial attachment of biofilms. Up-regulation of genes related to two component signal transduction systems and a denitrification enzyme pathway suggest that the B. pseudomallei high biofilm producer is able to sense the surrounding environmental conditions and regulate the production of extracellular polymeric substance matrix, a hallmark of microbial biofilm formation. CONCLUSIONS: The transcriptome profile described here provides the first comprehensive view of genes that contribute to the biofilm phenotype in B. pseudomallei.

Effects of palm oil tocotrienol-rich fraction on biochemical and morphological alterations of liver in fenitrothion-treated rats.

Indiscriminate application of organophosphate (OP) pesticides has led to environmental pollution and severe health problems. The aim of the present study was to evaluate the effect of palm oil tocotrienol-rich fraction (TRF) on biochemical and morphological changes of the liver in rats treated with fenitrothion (FNT), a type of OP pesticide. A total of 28 male Sprague-Dawley rats were divided into four groups; control group, TRF-supplemented group, FNT-treated group and TRF+FNT group. TRF (200 mg/kg) was supplemented 30 minutes prior to FNT (20 mg/kg) administration, both orally for 28 consecutive days. Following 28 days of treatment, plasma biochemical changes and liver morphology were evaluated. The body and absolute liver weights were significantly elevated in TRF+FNT group compared to FNT group. TRF administration significantly decreased the total protein level and restored the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in TRF + FNT group. In contrast, total bilirubin level, γ-glutamyltranferase (GGT) and cholinesterase activity in TRF + FNT group did not significantly differ from FNT group. Administration of TRF also prevented FNT-induced morphological changes of liver as observed by electron microscope. In conclusion, TRF supplementation showed potential protective effect towards biochemical and ultrastructural changes in liver induced by FNT.

Application of Artificial Intelligence in Cone-Beam Computed Tomography for Airway Analysis: A Narrative Review.

Cone-beam computed tomography (CBCT) has emerged as a promising tool for the analysis of the upper airway, leveraging on its ability to provide three-dimensional information, minimal radiation exposure, affordability, and widespread accessibility. The integration of artificial intelligence (AI) in CBCT for airway analysis has shown improvements in the accuracy and efficiency of diagnosing and managing airway-related conditions. This review aims to explore the current applications of AI in CBCT for airway analysis, highlighting its components and processes, applications, benefits, challenges, and potential future directions. A comprehensive literature review was conducted, focusing on studies published in the last decade that discuss AI applications in CBCT airway analysis. Many studies reported the significant improvement in segmentation and measurement of airway volumes from CBCT using AI, thereby facilitating accurate diagnosis of airway-related conditions. In addition, these AI models demonstrated high accuracy and consistency in their application for airway analysis through automated segmentation tasks, volume measurement, and 3D reconstruction, which enhanced the diagnostic accuracy and allowed predictive treatment outcomes. Despite these advancements, challenges remain in the integration of AI into clinical workflows. Furthermore, variability in AI performance across different populations and imaging settings necessitates further validation studies. Continued research and development are essential to overcome current challenges and fully realize the potential of AI in airway analysis.

The role of DNA methylation and DNA methyltransferases (DNMTs) as potential biomarker and therapeutic target in non-small cell lung cancer (NSCLC).

Lung cancer as the second most death cancer reported cases is becoming a major threat to the global healthcare system. With the different subtypes of lung cancer and their limited therapy options due to the lack of targetable genes, rising cases of treatment resistance further complicate the management. The majority of the reported lung cancer cases are categorised as non-small cell lung cancer (NSCLC) which is highly associated with tobacco smoking. Tumorigenesis and cancer progression have also been associated with epigenetics. Epigenetics is responsible for cancer gene regulation and its reversible mechanisms attract the current trend of cancer management research. One of the most studied mechanisms is DNA methylation which can influence the cancer gene transcription outcomes. The enzyme, DNA methyltransferases (DNMTs) play a role in regulating the whole process of DNA methylation. Thus, abnormalities in DNMTs can lead to aberrant methylation patterns which then disturb the gene regulation and cellular functions as a whole. In this review, NSCLC subtypes are discussed with the current research trend of studies involving DNA methylation mechanism as a potential diagnostic and prognostic cancer biomarker. As DNMTs expression influences the methylation pattern, our review also outlined the abnormal pattern of DNMTs and its potential therapeutic target for NSCLC to restore the aberrant gene regulation and produce a better prognosis.

Randomized controlled trial to compare the efficacy and safety of oral paricalcitol with oral calcitriol in dialysis patients with secondary hyperparathyroidism.

AIM: The objective of the study was to compare the efficacy and safety of oral paricalcitol with oral calcitriol for treating secondary hyperparathyroidism. METHODS: We conducted the first multicenter open-labelled parallel group randomized controlled trial in 66 patients on dialysis. Patients were randomized to paricalcitol or calcitriol at a 3:1 dose ratio and adjusted to maintain intact parathyroid hormone (iPTH) level between 150-300 pg/mL, serum calcium ≤2.74 mmol/L and calcium-phosphate product ≤5.63 mmol(2) /L(2). The primary end point was the proportion of patients who achieved >30% reduction in iPTH. RESULTS: At 24 weeks, 22 (61.1%) patients in the paricalcitol and 22 (73.3%) in the calcitriol group had achieved the primary end-point (P-value = 0.29). The cumulative proportion of patients who achieved the end-point at 6 weeks, 12 weeks and 24 weeks were 50%, 80.6% and 86.1%, respectively, in paricalcitol and 53.3%, 86.7% and 86.7%, respectively, in the calcitriol group (P-value = 0.67). Median time to the end-point was 6 weeks in both groups. There were no significant differences in iPTH level at any time during the study. The median reduction in iPTH at 24 weeks was 48.4% in the paricalcitol group and 41.9% in the calcitriol group (P-value = 0.6). The median maximal iPTH reduction was 77.1% (paricalcitol) and 83.7% (calcitriol), P-value = 0.3. Serum calcium and incidence of hypercalcaemia did not differ between groups. 16.7% of patients in both groups had at least one episode of hypercalcaemia (serum calcium >2.74 mmol/L). Other adverse events were similar between groups. CONCLUSION: Our study suggests that oral paricalcitol has similar efficacy and safety to oral calcitriol.

Antioxidant Activity of Tocotrienol Rich Fraction Prevents Fenitrothion-induced Renal Damage in Rats.

Fenitrothion (FNT) is an organophosphate compound widely used as pesticide in Malaysia. The present study aims to investigate effects of palm oil tocotrienol rich fraction (TRF) on the renal damage of FNT-treated rats. A total of 40 male Sprague Dawley rats were divided into 4 groups randomly, the control, TRF, FNT and FNT+TRF groups. FNT (20 mg/kg b.w.) and TRF (200 mg/kg b.w.) were given orally for 28 days continuously. Rats from the FNT+TRF group were supplemented with TRF 30 minutes prior to administration of FNT. Rats were sacrificed after 28 days, and the kidneys were removed for determination of oxidative stress and histological analysis. Plasma was collected for determination of blood creatinine and urea level. Statistical analysis showed that palm oil TRF has a protective effect against renal oxidative damage induced by FNT. In the FNT+TRF group, malondialdehyde and protein carbonyl levels were significantly lower, while the glutathione level as well as superoxide dismutase and catalase activities were significantly higher compared with the FNT-treated group (p<0.05). As for renal function, there was a markedly lower urea level (p<0.05) in the FNT+TRF group compared with the FNT-treated group, but there was no significant difference in creatinine level. Besides, total protein also showed no significant difference for all groups of rats (p>0.05). Histological evaluation also revealed that the FNT+TRF group had less glomerulus and renal tubule damage than the FNT-treated group. In conclusion, palm oil TRF was able to reduce oxidative stress and renal damage in FNT-treated rats.

Transcriptional landscape of Burkholderia pseudomallei cultured under environmental and clinical conditions.

Burkholderia pseudomallei, a Gram-negative pathogen, is the causative agent of melioidosis in humans. This bacterium can be isolated from the soil, stagnant and salt-water bodies, and human and animal clinical specimens. While extensive studies have contributed to our understanding of B. pseudomallei pathogenesis, little is known about how a harmless soil bacterium adapts when it shifts to a human host and exhibits its virulence. The bacterium's large genome encodes an array of factors that support the pathogen's ability to survive under stressful conditions, including the host's internal milieu. In this study, we performed comparative transcriptome analysis of B. pseudomallei cultured in human plasma versus soil extract media to provide insights into B. pseudomallei gene expression that governs bacterial adaptation and infectivity in the host. A total of 455 genes were differentially regulated; genes upregulated in B. pseudomallei grown in human plasma are involved in energy metabolism and cellular processes, whilst the downregulated genes mostly include fatty acid and phospholipid metabolism, amino acid biosynthesis and regulatory function proteins. Further analysis identified a significant upregulation of biofilm-related genes in plasma, which was validated using the biofilm-forming assay and scanning electron microscopy. In addition, genes encoding known virulence factors such as capsular polysaccharide and flagella were also overexpressed, suggesting an overall enhancement of B. pseudomallei virulence potential when present in human plasma. This ex vivo gene expression profile provides comprehensive information on B. pseudomallei's adaptation when shifted from the environment to the host. The induction of biofilm formation under host conditions may explain the difficulty in treating septic melioidosis.

Development of In Situ Product Recovery (ISPR) System Using Amberlite IRA67 for Enhanced Biosynthesis of Hyaluronic Acid by Streptococcus zooepidemicus.

High broth viscosity due to the accumulation of hyaluronic acid (HA) causes a limited yield of HA. It is a major problem of HA production using Streptococcus zooepidemicus. Extractive fermentation via in situ product recovery (ISPR) was utilized to enhance the HA production. Resins from Amberlite: IRA400 Cl; IRA900 Cl; IRA410 Cl; IRA402 Cl; and IRA67 were tested for the HA adsorption. IRA67 showed high adsorption capacity on HA. The study of the adsorption via a 2 L stirred tank bioreactor of S. zooepidemicus fermentation was investigated to elucidate the adsorption of HA onto IRA67 in dispersed and integrated internal column systems. The application of a dispersed IRA67 improved the HA production compared to the fermentation without resin addition by 1.37-fold. The HA production was further improved by 1.36-fold with an internal column (3.928 g/L) over that obtained with dispersed IRA67. The cultivation with an internal column shows the highest reduction of viscosity value after the addition of IRA67 resin: from 58.8 to 23.7 (mPa·s), suggesting the most effective ISPR of HA. The improved biosynthesis of HA indicated that an extractive fermentation by ISPR adsorption is effective and may streamline the HA purification.

Transitioning from Soil to Host: Comparative Transcriptome Analysis Reveals the Burkholderia pseudomallei Response to Different Niches.

Burkholderia pseudomallei, a soil and water saprophyte, is responsible for the tropical human disease melioidosis. A hundred years since its discovery, there is still much to learn about B. pseudomallei proteins that are essential for the bacterium's survival in and interaction with the infected host, as well as their roles within the bacterium's natural soil habitat. To address this gap, bacteria grown under conditions mimicking the soil environment were subjected to transcriptome sequencing (RNA-seq) analysis. A dual RNA-seq approach was used on total RNA from spleens isolated from a B. pseudomallei mouse infection model at 5 days postinfection. Under these conditions, a total of 1,434 bacterial genes were induced, with 959 induced in the soil environment and 475 induced in bacteria residing within the host. Genes encoding metabolism and transporter proteins were induced when the bacteria were present in soil, while virulence factors, metabolism, and bacterial defense mechanisms were upregulated during active infection of mice. On the other hand, capsular polysaccharide and quorum-sensing pathways were inhibited during infection. In addition to virulence factors, reactive oxygen species, heat shock proteins, siderophores, and secondary metabolites were also induced to assist bacterial adaptation and survival in the host. Overall, this study provides crucial insights into the transcriptome-level adaptations which facilitate infection by soil-dwelling B. pseudomallei. Targeting novel therapeutics toward B. pseudomallei proteins required for adaptation provides an alternative treatment strategy given its intrinsic antimicrobial resistance and the absence of a vaccine. IMPORTANCE Burkholderia pseudomallei, a soil-dwelling bacterium, is the causative agent of melioidosis, a fatal infectious disease of humans and animals. The bacterium has a large genome consisting of two chromosomes carrying genes that encode proteins with important roles for survival in diverse environments as well as in the infected host. While a general mechanism of pathogenesis has been proposed, it is not clear which proteins have major roles when the bacteria are in the soil and whether the same proteins are key to successful infection and spread. To address this question, we grew the bacteria in soil medium and then in infected mice. At 5 days postinfection, bacteria were recovered from infected mouse organs and their gene expression was compared against that of bacteria grown in soil medium. The analysis revealed a list of genes expressed under soil growth conditions and a different set of genes encoding proteins which may be important for survival, replication, and dissemination in an infected host. These proteins are a potential resource for understanding the full adaptation mechanism of this pathogen. In the absence of a vaccine for melioidosis and with treatment being reliant on combinatorial antibiotic therapy, these proteins may be ideal targets for designing antimicrobials to treat melioidosis.

Convolutional neural networks for automated tooth numbering on panoramic radiographs: A scoping review.

Purpose: The objective of this scoping review was to investigate the applicability and performance of various convolutional neural network (CNN) models in tooth numbering on panoramic radiographs, achieved through classification, detection, and segmentation tasks. Material and Methods: An online search was performed of the PubMed, Science Direct, and Scopus databases. Based on the selection process, 12 studies were included in this review. Results: Eleven studies utilized a CNN model for detection tasks, 5 for classification tasks, and 3 for segmentation tasks in the context of tooth numbering on panoramic radiographs. Most of these studies revealed high performance of various CNN models in automating tooth numbering. However, several studies also highlighted limitations of CNNs, such as the presence of false positives and false negatives in identifying decayed teeth, teeth with crown prosthetics, teeth adjacent to edentulous areas, dental implants, root remnants, wisdom teeth, and root canal-treated teeth. These limitations can be overcome by ensuring both the quality and quantity of datasets, as well as optimizing the CNN architecture. Conclusion: CNNs have demonstrated high performance in automated tooth numbering on panoramic radiographs. Future development of CNN-based models for this purpose should also consider different stages of dentition, such as the primary and mixed dentition stages, as well as the presence of various tooth conditions. Ultimately, an optimized CNN architecture can serve as the foundation for an automated tooth numbering system and for further artificial intelligence research on panoramic radiographs for a variety of purposes.

Metabolic routes affecting rubber biosynthesis in Hevea brasiliensis latex.

The cytosolic mevalonate (MVA) pathway in Hevea brasiliensis latex is the conventionally accepted pathway which provides isopentenyl diphosphate (IPP) for cis-polyisoprene (rubber) biosynthesis. However, the plastidic 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway may be an alternative source of IPP since its more recent discovery in plants. Quantitative RT-PCR (qRT-PCR) expression profiles of genes from both pathways in latex showed that subcellular compartmentalization of IPP for cis-polyisoprene synthesis is related to the degree of plastidic carotenoid synthesis. From this, the occurrence of two schemes of IPP partitioning and utilization within one species is proposed whereby the supply of IPP for cis-polyisoprene from the MEP pathway is related to carotenoid production in latex. Subsequently, a set of latex unique gene transcripts was sequenced and assembled and they were then mapped to IPP-requiring pathways. Up to eight such pathways, including cis-polyisoprene biosynthesis, were identified. Our findings on pre- and post-IPP metabolic routes form an important aspect of a pathway knowledge-driven approach to enhancing cis-polyisoprene biosynthesis in transgenic rubber trees.

Chemopreventive Effects of Oral Pterostilbene in Multistage Carcinogenesis of Skin Squamous Cell Carcinoma Mouse Model Induced by DMBA/TPA.

Skin squamous cell carcinoma (SCC) is a type of non-melanoma skin cancer. Pterostilbene is a natural compound proven to exhibit various pharmacological properties, including chemo-preventive effects. This study aimed to explore the chemo-preventive effect of oral pterostilbene during initiation, promotion or continuous on multistage skin SCC mouse models induced by 7,12-Dimethylbenz(a)anthracene (DMBA)/12-O-Tetradecanoylphorbol-13-acetate (TPA). The experimental design consists of five groups of female Institute of Cancer Research (ICR) mice, with two control groups of vehicle and cancer. Three oral pterostilbene groups consisted of orally administered pterostilbene during initiation, promotion, or continuously. Oral pterostilbene significantly reduced the number and volume of tumours. Oral pterostilbene demonstrated less severe skin histology changes compared to the cancer control group, with less pleomorphic in the cells and nuclei, and the basement membrane remained intact. Our results showed fewer invasive tumours in oral PT-treated groups than in cancer groups that displayed mitotic bodies, highly pleomorphic cells and nuclei, and basement membrane invasion. The cell proliferation marker (Ki-67) was reduced in oral pterostilbene-treated groups. Overall, oral pterostilbene is a promising chemo-preventive intervention due to its anti-initiation and anti-promotion on skin carcinogenesis. Thus, the potential molecular mechanisms of oral pterostilbene chemo-prevention agent should be explored.

Frequent Eating Out and 10-Year Cardiovascular Disease Risk: Evidence from a Community Observatory in Malaysia.

Despite increasing mortality rates from cardiovascular diseases (CVDs) in low- and middle-income countries, information on the estimation of 10-year CVD risk remains to be sparse. Therefore, this study was aimed at predicting the 10-year CVD risk among community dwellers in Malaysia and at identifying the association of distal (socioeconomic characteristics) and proximal (lifestyle practices) factors with 10-year CVD risk. We calculated the 10-year CVD risk score among 11,897 eligible respondents from the community health survey conducted by the South East Asia Community Observatory (SEACO) using the Framingham risk score (FRS). The findings indicate that 28% of respondents have a high chance of having CVD within the next ten years. After adjusting for the age of respondents, demographic and socioeconomic factors such as gender, ethnicity, marital status, education, income, and occupation had an association with the 10-year CVD risk. In addition, frequent eating out had an association with 10-year CVD risk, while physical activity was found to have no association with predicted CVD risk. CVD remained among the top five mortality causes in Malaysia. Health promotion strategies should emphasize the importance of having home-cooked meals as a healthy dietary behavior, to reduce the mortality rate among Malaysians due to CVDs.