Setting research priorities for global pandemic preparedness: An international consensus and comparison with ChatGPT's output.

Background: In this priority-setting exercise, we sought to identify leading research priorities needed for strengthening future pandemic preparedness and response across countries. Methods: The International Society of Global Health (ISoGH) used the Child Health and Nutrition Research Initiative (CHNRI) method to identify research priorities for future pandemic preparedness. Eighty experts in global health, translational and clinical research identified 163 research ideas, of which 42 experts then scored based on five pre-defined criteria. We calculated intermediate criterion-specific scores and overall research priority scores from the mean of individual scores for each research idea. We used a bootstrap (n = 1000) to compute the 95% confidence intervals. Results: Key priorities included strengthening health systems, rapid vaccine and treatment production, improving international cooperation, and enhancing surveillance efficiency. Other priorities included learning from the coronavirus disease 2019 (COVID-19) pandemic, managing supply chains, identifying planning gaps, and promoting equitable interventions. We compared this CHNRI-based outcome with the 14 research priorities generated and ranked by ChatGPT, encountering both striking similarities and clear differences. Conclusions: Priority setting processes based on human crowdsourcing - such as the CHNRI method - and the output provided by ChatGPT are both valuable, as they complement and strengthen each other. The priorities identified by ChatGPT were more grounded in theory, while those identified by CHNRI were guided by recent practical experiences. Addressing these priorities, along with improvements in health planning, equitable community-based interventions, and the capacity of primary health care, is vital for better pandemic preparedness and response in many settings.

Changes in Mitochondrial Epigenome in Type 2 Diabetes Mellitus.

Type 2 Diabetes Mellitus is a major chronic metabolic disorder in public health. Due to mitochondria's indispensable role in the body, its dysfunction has been implicated in the development and progression of multiple diseases, including Type 2 Diabetes mellitus. Thus, factors that can regulate mitochondrial function, like mtDNA methylation, are of significant interest in managing T2DM. In this paper, the overview of epigenetics and the mechanism of nuclear and mitochondrial DNA methylation were briefly discussed, followed by other mitochondrial epigenetics. Subsequently, the association between mtDNA methylation with T2DM and the challenges of mtDNA methylation studies were also reviewed. This review will aid in understanding the impact of mtDNA methylation on T2DM and future advancements in T2DM treatment.

Potential of medicinal plants to ameliorate neovascularization activities in diabetes: A systematic review.

Hyperglycemia in diabetes mediates the release of angiogenic factors, oxidative stress, hypoxia, and inflammation, which in turn stimulate angiogenesis. Excessive angiogenesis can cause diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. All of these complications are debilitating, which may lead to an increased susceptibility to lower-limb amputations due to ulcerations and infections. In addition, microvascular alterations, segmental demyelination, and endoneurial microangiopathy may cause progressive deterioration ultimately leading to kidney failure and permanent blindness. Some medicinal plants have potent anti-angiogenic, antioxidant or anti-inflammatory properties that can ameliorate angiogenesis in diabetes. The purpose of this systematic review is to demonstrate the potential of medicinal plants in ameliorating the neovascularization activities in diabetes. Manuscripts were searched from PubMed, Science Direct, and Scopus databases, and Google Scholar was used for searching additional papers. From 1862 manuscripts searched, 1854 were excluded based on inclusion and exclusion criteria and 8 were included into this systematic review, whereas the required information was extracted and summarized. All identified medicinal plants decreased the high blood glucose levels in diabetes, except the aqueous extract of Lonicerae japonicae flos (FJL) and Vasant Kusumakar Ras. They also increased the reduced body weight in diabetes, except the aqueous extract of FL and total lignans from Fructus arctii. However, methanolic extract of Tinospora cordifolia and Vasant Kusumakar Ras were not tested for their ability to affect the body weight. Besides, all medicinal plants identified in this systematic review decreased the vascular endothelial growth factor (VEGF) protein expression and vasculature activity demonstrated by histopathological examination indicating promising anti-angiogenic properties. All medicinal plants identified in this systematic review have a potential to ameliorate neovascularization activities in diabetes by targeting the mechanistic pathways related to oxidative stress, inflammation, and angiogenesis.

Comparative Analysis of In Vitro Enzyme Inhibitory Activities and Phytochemicals from Platycladus orientalis (L.) Franco via Solvent Partitioning Method.

The extraction of plant bioactive compounds from Platycladus orientalis (L.) Franco remains a great challenge due to the different chemical groups. This study aimed to compare the bioactive compounds with enzyme inhibitory effect from P. orientalis via solvent partitioning method. Dried leaf samples were macerated and fractionated with six solvents of different polarities. The phenolic, flavonoid, tannin, saponin, alkaloid and pharmacological activities including anti-inflammatory, anti-diabetic, antioxidant and anti-glycation potential were compared across the six plant fractions. Toxicity assessment was performed with an in vivo brine shrimp model. The varying levels of bioactive compounds in ethyl acetate (phenolics, flavonoids), hexane (saponins, tannins) and chloroform (alkaloids) fractions clearly demonstrated the significant impact of solvent polarity on the extraction of bioactive compounds. The reducing potential (r = 0.67), IC50 of α-amylase inhibition (r = -0.71), IC50 of advanced glycation end-product inhibition (r = -0.93) and dicarbonyl compound inhibition (r = 0.57) in the plant fractions were correlated (p<0.05) with the flavonoids. Besides, the alkaloid, saponin and tannin were associated with cyclooxygenase-1 inhibitory activity. Principal component analysis confirmed that solvent polarity (23.9%) and plant extraction yield (37.1%) collectively contributed to 61% of bioactivity variation in P. orientalis. Among the six plant fractions, ethyl acetate fraction exhibited relatively high anti-inflammatory, anti-diabetic, antioxidant and anti-glycation potential while the non-toxic methanolic and aqueous fractions displayed optimal hyaluronidase and lipoxygenase inhibitory activities, respectively. The current study has identified semi-polar ethyl acetate fraction of P. orientalis as a good alternative source of bioactive compounds for future pharmaceutical product development.

Peperomia pellucida (L.) Kunth and eye diseases: A review on phytochemistry, pharmacology and toxicology.

Peperomia pellucida (L.) Kunth is a medicinal plant used to manage inflammatory illnesses such as conjunctivitis, and gastrointestinal and respiratory tract disorders in tropical and subtropical regions. However, little is known about its pharmacological mechanism of action against eye diseases. This review aims to critically discuss the phytochemistry, pharmacology and toxicology of P. pellucida as well as its roles in the treatment of cataract, glaucoma and diabetic retinopathy. Recent developments in the uses of P. pellucida for healthcare and nutraceutical products by the pharmaceutical industry are also covered in this review. For this review, a literature search was performed with PubMed, ScienceDirect, SciFinder Scholar and Scopus databases, using relevant keywords. Among the various phytochemicals identified from P. pellucida, ß-caryophyllene, carotol, dillapiole, ellagic acid, pellucidin A, phytol and vitexin exhibit strong pharmacological activities within the mitogen-activated protein kinase and nuclear factor-κB signalling pathways in inflammatory eye diseases. The antihypertensive, anti-inflammatory, antioxidant, antihyperglycemic and anti-angiogenic activities displayed by P. pellucida extracts in many in vitro, in vivo and clinical studies suggest its potential role in the management of inflammatory eye diseases. P. pellucida extract was non-toxic against normal cell lines but displayed mild toxicity in animal models. The growing public interest in P. pellucida has inspired the nutraceutical and pharmaceutical industries to process the plant into health products. Although the potential pharmacological mechanisms against eye diseases have been summarized, further studies of the interactions among constituent phytochemicals from P. pellucida within various signalling pathways shall support the use of the plant as an alternative therapeutic source.

Comparative analyses on radical scavenging and cytotoxic activity of phenolic and flavonoid content from selected medicinal plants.

This study aimed to compare the total phenolic (TPC), flavonoid (TFC), radical scavenging and cytotoxic activities in the aqueous methanolic extracts of Angelica sinensis, Dioscorea polystachya, Ginkgo biloba, Glycyrrhiza uralensis and Lycium barbarum with two dietary plants: Brassica oleracea and Zingiber officinale. The TPC and TFC in medicinal plant extracts were 12-93% lower than Z. officinale as follows: L. barbarum > G. uralensis > A. sinensis > G. biloba > D. polystachya. The decreasing radical scavenging activity in medicinal plant extracts shared similar trend: G. uralensis > L. barbarum > A. sinensis > G. biloba > D. polystachya. Both TPC and TFC were positively correlated with radical scavenging and cytotoxic activities. All medicinal plants were considered inactive (LC50 > 0.2 mg/ml) and safe for consumption. The TPC, TFC, radical scavenging and cytotoxic activities in the medicinal plants were plant-part dependant, in particular L. barbarum and G. uralensis.

Peperomia pellucida (L.) Kunth herbal tea: Effect of fermentation and drying methods on the consumer acceptance, antioxidant and anti-inflammatory activities.

This study aimed to compare the effect of fermentation and drying on the organoleptic characteristic, total phenolic content, antioxidant and anti-inflammatory activities of Peperomia pellucida (L.) Kunth tea with commercial Camellia sinensis tea. The phenolic content, antioxidant and anti-inflammatory activities in P. pellucida were significantly (p < 0.05) lower than C. sinensis, irrespective of the fermentation and drying methods. Although fermentation decreased the total phenolics, flavonoids and antioxidant activity in both P. pellucida and C. sinensis teas, the anti-inflammatory potential of P. pellucida was significantly (p < 0.05) improved. Principle component analysis revealed that fermentation and drying methods contributed to respective 42.3% and 27.2% of activity variation in P. pellucida. The browning index was positively correlated with fermentation index (r = 0.670, p < 0.05) of leaves samples. Overall, unfermented and fermented P. pellucida leaves were best dried with microwaving and freeze drying, respectively for optimal antioxidant and anti-inflammatory activities with favorable consumer's acceptance.

In vitro digestion and domestic cooking improved the total antioxidant activity and carbohydrate-digestive enzymes inhibitory potential of selected edible mushrooms.

This study aimed to investigate the effect of in vitro digestion on the antioxidant activity and carbohydrate-digestive enzymes inhibitory potential of five edible mushrooms after subjected to four domestic cooking; namely, boiling, microwaving, steaming and pressure-cooking. The water extracts of raw (uncooked), cooked and in vitro digested mushrooms were compared for their water-soluble phenolic content (WPC), total flavonoid content (TFC), ferric reducing antioxidant power (FRAP), radical scavenging activity (TEAC and DPPH), anti-α-amylase and anti-α-glucosidase activities. Among the raw samples, Lentinula edodes possessed the highest antioxidant activities (FRAP, TEAC, DPPH) and WPC while Pleurotus sajor-caju displayed the highest TFC, anti-α-amylase and anti-α-glucosidase activities. The antioxidant and carbohydrate-digestive enzyme inhibitory activities significantly varied according to mushroom species and cooking methods applied. Short duration of microwaving (Agaricus bisporus and Flammulina velutipes), boiling (Auricularia polytricha) and pressure cooking (L. edodes and P. sajor-caju) yielded the best antioxidant and carbohydrate-digestive enzymes inhibition values in the mushroom extracts. TFC was positively correlated with the antioxidant activities and anti-α-glucosidase activity in the mushroom extracts. In vitro digestion significantly improved the total antioxidant and anti-α-glucosidase activities but decreased the anti-α-amylase activity in the cooked mushroom extracts. Principle component analysis showed that in vitro digestion and the cooking process accounted for respective 48.9% and 19.7% of variation in the observed activities. Domestic cooking and in vitro digestion could potentiate the total antioxidant and carbohydrate-digestive enzymes inhibitory activities in the selected water extract of edible mushrooms.

Impact of optimised cooking on the antioxidant activity in edible mushrooms.

This study aimed to investigate the effect of four cooking methods with different durations on the in vitro antioxidant activities of five edible mushrooms, namely Agaricus bisporus, Flammulina velutipes, Lentinula edodes, Pleurotus ostreatus and Pleurotus eryngii. Among the raw samples, A. bisporus showed the highest total antioxidant activity (reducing power and radical scavenging), total flavonoid, ascorbic acid and water soluble phenolic contents. Short-duration steam cooking (3 min) increased the total flavonoid and ascorbic acid while prolonged pressure cooking (15 min) reduced the water soluble phenolic content in the mushrooms. The retention of antioxidant value in the mushrooms varied with the variety of mushroom after the cooking process. The cooking duration significantly affected the ascorbic acid in the mushrooms regardless of cooking method. To achieve the best antioxidant values, steam cooking was preferred for F. velutipes (1.5 min), P. ostreatus (4.5 min) and L. edodes (4.5 min) while microwave cooking for 1.5 min was a better choice for A. bisporus. Pressure cooked P. eryngii showed the best overall antioxidant value among the cooked samples. Optimised cooking method including pressure cooking could increase the antioxidant values in the edible mushrooms.

Proteomic analysis of heat treated bitter gourd (Momordica charantia L. var. Hong Kong Green) using 2D-DIGE.

This study aimed to investigate the changes in the proteome of bitter gourd prior to and after subjecting to boiling and microwaving. A comparative analysis of the proteome profiles of raw and thermally treated bitter gourds was performed using 2D-DIGE. The protein content and number of protein spots in raw sample was higher when compared to the cooked samples. Qualitative analysis revealed that 103 (boiled sample) and 110 (microwaved sample) protein spots were up regulated whereas 120 (boiled sample) and 107 (microwaved sample) protein spots were down regulated. Ten protein spots with the highest significant fold change in the cooked samples were involved in carbohydrate/energy metabolisms and stress responses. Small heat shock proteins, superoxide dismutase, quinone oxidoreductase, UDP-glucose pyrophosphorylase and phosphoglycerate kinase play a role in heat-stress-mediated protection of bitter gourd. This study suggests that appropriate heat treatment (cooking methods) can lead to induction of selected proteins in bitter gourd.

Soluble receptor for advanced glycation end-product (sRAGE)/pentosidine ratio: a potential risk factor determinant for type 2 diabetic retinopathy.

This study aims to investigate potential diabetic retinopathy (DR) risk factors by evaluating the circulating levels of pentosidine, soluble receptor for advanced glycation end-product (sRAGE), advanced oxidation protein product (AOPP) as well as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities in DR patients. A total of 235 healthy controls, 171 type 2 diabetic without retinopathy (DNR) and 200 diabetic retinopathy (DR) patients were recruited. Plasma was extracted for the estimation of pentosidine, sRAGE, AOPP levels and GPx activity whereas peripheral blood mononuclear cells were disrupted for SOD activity measurement. DNR and DR patients showed significantly higher levels of plasma pentosidine, sRAGE and AOPP but lower GPx and SOD activities when compared to healthy controls. The sRAGE/pentosidine ratio in DR patients was significantly lower than the ratio detected in DNR patients. Proliferative DR patients had significantly higher levels of plasma pentosidine, sRAGE, AOPP and sRAGE/pentosidine ratio than non-proliferative DR patients. High HbA1c level, long duration of diabetes and low sRAGE/pentosidine ratio were determined as the risk factors for DR. This study suggests that sRAGE/pentosidine ratio could serve as a risk factor determinant for type 2 DR as it has a positive correlation with the severity of DR.

Receptor for advanced glycation end-product (RAGE) gene polymorphism 2245G/A is associated with pro-inflammatory, oxidative-glycation markers and sRAGE in diabetic retinopathy.

BACKGROUND: Receptor for advanced glycation end-product (RAGE) gene polymorphism 2245G/A is associated with diabetic retinopathy (DR). However, the mechanism on how it affects the disease development is still unclear. AIM: This study aims to investigate the relationship between 2245G/A RAGE gene polymorphism and selected pro-inflammatory, oxidative-glycation markers in DR patients. METHODS: A total of 371 unrelated type 2 diabetic patients [200 with retinopathy, 171 without retinopathy (DNR)] and 235 healthy subjects were recruited. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism method followed by DNA sequencing. The nuclear and cytosolic extracts from peripheral blood mononuclear cells were used for nuclear factor kappa B (NF-κB) p65 and superoxide dismutase activity measurement respectively. Plasma was used for glutathione peroxidase activity, advanced oxidation protein product (AOPP), monocyte chemoattractant protein (MCP)-1, pentosidine and soluble RAGE (sRAGE) measurements. RESULTS: DR patients with 2245GA genotype had significantly elevated levels of activated NF-κB p65, plasma MCP-1, AOPP and pentosidine but lower level of sRAGE when compared to DR patients with wild-type 2245GG. CONCLUSION: The RAGE gene polymorphism 2245G/A is associated with pro-inflammatory, oxidative-glycation markers and circulating sRAGE in DR patients. Patients with 2245GA RAGE genotype could aggravate DR possibly via NF-κB mediated inflammatory pathway.

Attenuated levels of pro-inflammatory markers in diabetic retinopathy patients undergoing treatment with antihyperglycemic and antihypertensive drugs.

OBJECTIVE: This study aimed to assess the circulating levels of activated nuclear factor kappa B p65 and monocyte chemotactic protein-1 in diabetic retinopathy patients who were taking antihyperglycemic and antihypertensive drugs. METHODS: In total, 235 healthy controls and 371 Type 2 diabetic patients [171 without retinopathy (DNR) and 200 patients with retinopathy (diabetic retinopathy)] were recruited for this study. Plasma and the nuclear fraction of peripheral blood mononuclear cells were isolated for the quantification of the monocyte chemotactic protein-1 and nuclear factor kappa B p65 levels, respectively. RESULTS: Non-medicated diabetic retinopathy patients had significantly higher levels of activated nuclear factor kappa B p65 and plasma monocyte chemotactic protein-1 than DNR patients. Diabetic retinopathy patients who were taking antihyperglycemic and antihypertensive drugs showed significant reductions in both the nuclear factor kappa B p65 and monocyte chemotactic protein-1 levels compared with the non-medicated patients. CONCLUSION: This study demonstrated the significant attenuation of both the nuclear factor kappa B p65 and circulating monocyte chemotactic protein-1 levels in diabetic retinopathy patients taking antihyperglycemic and antihypertensive drugs.

Attenuated levels of pro-inflammatory markers in diabetic retinopathy patients undergoing treatment with antihyperglycemic and antihypertensive drugs

OBJECTIVE: This study aimed to assess the circulating levels of activated nuclear factor kappa B p65 and monocyte chemotactic protein-1 in diabetic retinopathy patients who were taking antihyperglycemic and antihypertensive drugs. METHODS: In total, 235 healthy controls and 371 Type 2 diabetic patients [171 without retinopathy (DNR) and 200 patients with retinopathy (diabetic retinopathy)] were recruited for this study. Plasma and the nuclear fraction of peripheral blood mononuclear cells were isolated for the quantification of the monocyte chemotactic protein-1 and nuclear factor kappa B p65 levels, respectively. RESULTS: Non-medicated diabetic retinopathy patients had significantly higher levels of activated nuclear factor kappa B p65 and plasma monocyte chemotactic protein-1 than DNR patients. Diabetic retinopathy patients who were taking antihyperglycemic and antihypertensive drugs showed significant reductions in both the nuclear factor kappa B p65 and monocyte chemotactic protein-1 levels compared with the non-medicated patients. CONCLUSION: This study demonstrated the significant attenuation of both the nuclear factor kappa B p65 and circulating monocyte chemotactic protein-1 levels in diabetic retinopathy patients taking antihyperglycemic and antihypertensive drugs.

Investigation of SLC2A1 26177A/G gene polymorphism via high resolution melting curve analysis in Malaysian patients with diabetic retinopathy.

PURPOSE: In this study, we aimed to investigate the possible association between SLC2A1 26177A/G polymorphism and diabetic retinopathy (DR) in Malaysian patients with type 2 diabetes. METHODS: Genomic DNA was extracted from 211 Malaysian type 2 diabetic patients (100 without retinopathy [DNR], 111 with retinopathy) and 165 healthy controls. A high resolution melting assay developed in this study was used to detect SLC2A1 26177A/G polymorphism followed by statistical analysis. RESULTS: A statistically significant difference in 26177G minor allele frequency between healthy controls (19.7 %) and total patient group (26.1 %) (p<0.05, Odd ratio = 1.437, 95% Confidence interval = 1.015-2.035) as well as between healthy controls (19.7 %) and DNR patients (27.5%) (p<0.05, Odd ratio = 1.546, 95% Confidence interval = 1.024-2.336) was shown in this study. However, when compared between DR and DNR patients, there was no significant difference (p>0.05). CONCLUSIONS: This is the first study which shows that SLC2A1 26177G allele is associated with type 2 diabetes in Malaysian population but not with DR.

Association analysis of -429T/C and -374T/A polymorphisms of receptor of advanced glycation end products (RAGE) gene in Malaysian with type 2 diabetic retinopathy.

Conflicting results have been reported in different populations on the association between two particular RAGE gene polymorphisms (-429T/C and -374T/A) and retinopathy in diabetic patients. Therefore this study was designed to assess the association between both gene polymorphisms with retinopathy in Malaysian diabetic patients. A total of 342 type 2 diabetic patients [171 without retinopathy (DNR) and 171 with retinopathy (DR)] and 235 healthy controls were included in this study. Genomic DNA was obtained from blood samples and the screening for the gene polymorphisms was done using polymerase chain reaction-restriction fragment length polymorphism approach. Overall, the genotype distribution for both polymorphisms was not statistically different (p>0.05) among the control, DNR and DR groups. The -429C minor allele frequency of DR group (12.0%) was not significantly different (p>0.05) when compared to DNR group (16.1%) and healthy controls (11.3%). The -374A allele frequency also did not differ significantly between the control and DNR (p>0.05), control and DR (p>0.05) as well as DNR and DR groups (p>0.05). This is the first study report on RAGE gene polymorphism in Malaysian DR patients. In conclusion, -429T/C and -374T/A polymorphisms in the promoter region of RAGE gene were not associated with Malaysian type 2 DR patients.

2245G/A polymorphism of the receptor for advanced glycation end-products (RAGE) gene is associated with diabetic retinopathy in the Malaysian population.

BACKGROUND/AIMS: The receptor for advanced glycation end-products (RAGE) has been implicated in the pathogenesis of diabetic microvascular complications. The aim of this study was to investigate the association between 2245G/A gene polymorphism of the RAGE gene and retinopathy in Malaysian type 2 diabetic patients. METHODS: 342 unrelated type 2 diabetic patients (171 with retinopathy (DR), 171 without retinopathy (DNR)) and 235 unrelated healthy subjects from all over Malaysia were recruited for this study. Genomic DNA was isolated from 3 ml samples of whole blood using a modified conventional DNA extraction method. The genotype and allele frequencies of 2245G/A were studied using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: A statistically significant difference in 2245A minor allele frequency was found between control (5.5%) and DR groups (15.2%) (p<0.001, OR=3.06, 95% CI 1.87 to 5.02) as well as between DNR (8.2%) and DR (15.2%) groups (p<0.01, OR=2.01, 95% CI 1.24 to 3.27). However, when the frequency was compared between control and DNR groups, there was no significant difference (p>0.05). CONCLUSIONS: This is the first study that shows an association between the 2245A allele of the RAGE gene and development of diabetic retinopathy in the Malaysian population.

Customized cooking method improves total antioxidant activity in selected vegetables.

The present study compares water-soluble phenolic content (WPC) and antioxidant activities in Chinese long bean (Vigna unguiculata), bitter gourd (Momordica charantia), water convolvulus (Ipomoea aquatica) and broccoli (Brassica olearacea) prior to and after subjecting to boiling, microwaving and pressure cooking. The total antioxidant activity was increased in cooked water convolvulus, broccoli and bitter gourd, estimated based on the ferric reducing antioxidant power, the Trolox equivalent antioxidant capacity and 2,2-diphenyl-1-picryl-hydrazyl radical scavenging activity. Pressure cooking did not cause any significant decline in the antioxidant property. Boiling generally improved the overall antioxidant activity in all the vegetables. Correlation analysis suggests that WPC contributed to significant antioxidant activities in these vegetables. Thus, prudence in selecting an appropriate cooking method for different vegetables may improve or preserve their nutritional value.