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Fundamental Research May 2024Corona virus disease 2019 (COVID-19) has exerted a profound adverse impact on human health. Studies have demonstrated that aerosol transmission is one of the major... (Review)
Review
Corona virus disease 2019 (COVID-19) has exerted a profound adverse impact on human health. Studies have demonstrated that aerosol transmission is one of the major transmission routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pathogenic microorganisms such as SARS-CoV-2 can survive in the air and cause widespread infection among people. Early monitoring of pathogenic microorganism transmission in the atmosphere and accurate epidemic prediction are the frontier guarantee for preventing large-scale epidemic outbreaks. Monitoring of pathogenic microorganisms in the air, especially in densely populated areas, may raise the possibility to detect viruses before people are widely infected and contain the epidemic at an earlier stage. The multi-scale coupled accurate epidemic prediction system can provide support for governments to analyze the epidemic situation, allocate health resources, and formulate epidemic response policies. This review first elaborates on the effects of the atmospheric environment on pathogenic microorganism transmission, which lays a theoretical foundation for the monitoring and prediction of epidemic development. Secondly, the monitoring technique development and the necessity of monitoring pathogenic microorganisms in the atmosphere are summarized and emphasized. Subsequently, this review introduces the major epidemic prediction methods and highlights the significance to realize a multi-scale coupled epidemic prediction system by strengthening the multidisciplinary cooperation of epidemiology, atmospheric sciences, environmental sciences, sociology, demography, etc. By summarizing the achievements and challenges in monitoring and prediction of pathogenic microorganism transmission in the atmosphere, this review proposes suggestions for epidemic response, namely, the establishment of an integrated monitoring and prediction platform for pathogenic microorganism transmission in the atmosphere.
PubMed: 38933199
DOI: 10.1016/j.fmre.2023.05.022 -
Nutrients Jun 2024Depression is a major global health concern expected to worsen by 2030. In 2019, 28 million individuals were affected by depressive disorders. Dietary and supplemental... (Review)
Review
Depression is a major global health concern expected to worsen by 2030. In 2019, 28 million individuals were affected by depressive disorders. Dietary and supplemental vitamins show overall favorable preventative and therapeutic effects on depression. B vitamins are crucial for neurological function and mood regulation. Deficiencies in these vitamins are linked to depression. Studies on individual B vitamins show promise in improving depressive symptoms, particularly thiamin, riboflavin, niacin, and folate. Vitamin C deficiency may heighten depressive symptoms, but its exact role is not fully understood. Seasonal Affective Disorder (SAD) is associated with insufficient sunlight exposure and vitamin D deficiency. Vitamin D supplementation for SAD shows inconsistent results due to methodological variations. Further investigation is needed to understand the mechanisms of vitamins in depression treatment. Moreover, more research on SAD and light therapy's efficacy and underlying mechanisms involving photoreceptors, enzymes, and immune markers is needed. Although dietary and supplemental vitamins show overall favorable preventative and therapeutic effects on depression, dietitians treating psychiatric disorders face challenges due to diverse study designs, making direct comparisons difficult. Therefore, this article reviews the current literature to assess the role of dietary and supplemental vitamins in the prevention and treatment of depression. This review found that, although evidence supports the role of B vitamins and vitamins C and D in preventing and treating depression, further research is needed to clarify their mechanisms of action and determine the most effective intervention strategies.
Topics: Humans; Seasonal Affective Disorder; Vitamin D; Dietary Supplements; Vitamins; Depression; Adult; Ascorbic Acid; Vitamin B Complex; Vitamin D Deficiency; Female; Solubility
PubMed: 38931257
DOI: 10.3390/nu16121902 -
Molecules (Basel, Switzerland) Jun 2024Ultraviolet B (UVB) exposure can contribute to photoaging of skin. is rich in ursolic acid (UA), which is beneficial to the prevention of photoaging. Because UA is...
Ultraviolet B (UVB) exposure can contribute to photoaging of skin. is rich in ursolic acid (UA), which is beneficial to the prevention of photoaging. Because UA is hardly soluble in water, the extract (COE) was obtained using water as the antisolvent to separate the components containing UA from the crude extract of . The effect of COE on UVB damage was assessed using . The results showed that COE could increase the lifespan and enhance the antioxidant enzyme activity of exposed to UVB while decreasing the reactive oxygen species (ROS) level. At the same time, COE upregulated the expression of antioxidant-related genes and promoted the migration of SKN-1 to the nucleus. Moreover, COE inhibited the expression of the downstream gene and the extension of the lifespan in mutants exposed to UVB, indicating that SKN-1 was required for COE to function. Our findings indicate that COE mainly ameliorates the oxidative stress caused by UVB in via the SKN-1/Nrf2 pathway.
Topics: Animals; Caenorhabditis elegans; Triterpenes; Ursolic Acid; Ultraviolet Rays; Plant Extracts; Caenorhabditis elegans Proteins; Oxidative Stress; Cornus; Antioxidants; Reactive Oxygen Species; Skin Aging; Transcription Factors; DNA-Binding Proteins; Longevity; NF-E2-Related Factor 2
PubMed: 38930783
DOI: 10.3390/molecules29122718 -
Life (Basel, Switzerland) May 2024Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare disorders of heme biosynthesis characterized by severe cutaneous phototoxicity....
BACKGROUND
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare disorders of heme biosynthesis characterized by severe cutaneous phototoxicity. Afamelanotide, an α-melanocyte-stimulating hormone analogue, is the only approved treatment for protoporphyria and leads to increased light tolerance and improved quality of life (QoL). However, published experience with afamelanotide in the US is limited.
METHODS
Here, we report on all adults who received at least one dose of afamelanotide at the Massachusetts General Hospital Porphyria Center from 2021 to 2022. Changes in the time to phototoxic symptom onset, QoL, and laboratory parameters were assessed before and during treatment with afamelanotide.
RESULTS
A total of 29 patients with protoporphyria were included, 26 of whom (72.2%) received ≥2 afamelanotide implants. Among the patients who received ≥2 implants, the median time to symptom onset following sunlight exposure was 12.5 min (IQR, 5-20) prior to the initiation of afamelanotide and 120 min (IQR, 60-240) after treatment ( < 0.001). Improvements in QoL during afamelanotide treatment were measured using two QoL tools, with good correlation observed between these two instruments. Finally, we found no improvements in the median levels of metal-free erythrocyte protoporphyrin, plasma protoporphyrin, or liver biochemistries during versus prior to the initiation of afamelanotide treatment.
CONCLUSIONS
This study highlights a dramatic clinical benefit of afamelanotide in relation to light tolerance and QoL in protoporphyria, albeit without improvement in protoporphyrin levels or measures of liver function.
PubMed: 38929673
DOI: 10.3390/life14060689 -
International Journal of Molecular... Jun 2024UV-B is an important environmental factor that differentially affects plant growth and secondary metabolites. The effects of supplemental ultraviolet-B (sUV-B) exposure...
UV-B is an important environmental factor that differentially affects plant growth and secondary metabolites. The effects of supplemental ultraviolet-B (sUV-B) exposure (T1, 1.40 kJ·m·day; T2, 2.81 kJ·m·day; and T3, 5.62 kJ·m·day) on the growth biomass, physiological characteristics, and secondary metabolites were studied. Our results indicated that leaf thickness was significantly ( < 0.05) reduced under T3 relative to the control (natural light exposure, CK); The contents of 6-BA and IAA were significantly reduced ( < 0.05); and the contents of ABA, 10-deacetylbaccatin III, and baccatin III were significantly ( < 0.05) increased under T1 and T2. The paclitaxel content was the highest (0.036 ± 0.0018 mg·g) under T3. The cephalomannine content was significantly increased under T1. gene expression was upregulated under T1 and T3. The gene expressions of and were significantly ( < 0.05) upregulated under sUV-B exposure, and the gene expressions of , , and were significantly ( < 0.05) downregulated. A correlation analysis showed that the 6-BA content had a significantly ( < 0.05) positive correlation with gene expression. The IAA content had a significantly ( < 0.05) positive correlation with the gene expression of , , , and . The ABA content had a significantly ( < 0.05) positive correlation with gene expression. gene expression had a significantly ( < 0.05) positive correlation with the 10-deacetylbaccatin content. gene expression was positively correlated with the contents of baccatin III and cephalomannine. gene expression had a significantly ( < 0.01) positive correlation with the paclitaxel content. A factor analysis showed that the accumulation of paclitaxel content was promoted under T2, which was helpful in clarifying the accumulation of taxane compounds after sUV-B exposure.
Topics: Taxus; Taxoids; Ultraviolet Rays; Gene Expression Regulation, Plant; Paclitaxel; Plant Leaves; Bridged-Ring Compounds; Indoleacetic Acids; Plant Growth Regulators; Abscisic Acid; Alkaloids
PubMed: 38928114
DOI: 10.3390/ijms25126407 -
Cancers Jun 2024Human papillomavirus (HPV) has been implicated in various cancers, including those affecting the skin. The study assessed the long-term risk of skin cancer associated...
Synergistic Effect of Human Papillomavirus and Environmental Factors on Skin Squamous Cell Carcinoma, Basal Cell Carcinoma, and Melanoma: Insights from a Taiwanese Cohort.
Human papillomavirus (HPV) has been implicated in various cancers, including those affecting the skin. The study assessed the long-term risk of skin cancer associated with HPV infection in Taiwan region, using data from the National Health Insurance Research Database between 2007 and 2015. Our analysis revealed a significant increase in skin cancer risk among those with HPV, particularly for squamous cell carcinoma (SCC), the subtype with the highest observed adjusted hazard ratio (aHR) = 5.97, 95% CI: 4.96-7.19). The overall aHR for HPV-related skin cancer was 5.22 (95% CI: 4.70-5.80), indicating a notably higher risk in the HPV-positive group. The risk of skin cancer was further stratified by type, with basal cell carcinoma (aHR = 4.88, 95% CI: 4.14-5.74), and melanoma (aHR = 4.36, 95% CI: 2.76-6.89) also showing significant associations with HPV. The study also highlighted regional variations, with increased risks in southern Taiwan and the Kaohsiung-Pingtung area. Key findings emphasize the importance of sun protection, particularly in regions of high UV exposure and among individuals in high-risk occupations. This research contributes to a better understanding of the complex interactions between HPV and skin cancer risk, reinforcing the importance of preventive strategies in public health.
PubMed: 38927988
DOI: 10.3390/cancers16122284 -
Photochemistry and Photobiology Jun 2024Tree shade, particularly shade that obscures direct sunlight near peak periods of midday solar exposure can have a pronounced effect on potentially harmful ultraviolet...
Tree shade, particularly shade that obscures direct sunlight near peak periods of midday solar exposure can have a pronounced effect on potentially harmful ultraviolet radiation, and in turn, strongly influence the maximum daily UV index (UVI). In this study, the seasonal influence of tree shade on the UVI is evaluated from 210 hemispherical sky view images collected alongside public walkways and footpaths from 10 residential Brisbane suburbs. The effective sidewalk UV index is calculated underneath planted tree canopies, adjacent residential gardens, buildings and background tree species. Results are presented with respect to seasonal variations in the diurnal solar elevation for each month of the year at Brisbane's latitude. The research also examines the total reduction in UVI due to the presence of individual tree species, showing reductions in the midday UVI of up to 91% of an equivalent unimpeded sky hemisphere when overhead tree canopies are present. Important footpath tree species for peak midday UVI mitigation include Pongamia pinnata, Xanthostemon chrysanthus, Senna siamea, and Libidibia ferrea. The planting and maintenance of existing tree species already growing alongside residential Brisbane streets will improve the shade characteristics of suburbs and enhance UV protection for local residents.
PubMed: 38926941
DOI: 10.1111/php.13988 -
Cancer Jun 2024Phosphatidylinositol 3-kinase (PI3K) inhibitors transformed management of various malignancies. This study preclinically characterized TQ-B3525 (dual PI3Kα/δ...
BACKGROUND
Phosphatidylinositol 3-kinase (PI3K) inhibitors transformed management of various malignancies. This study preclinically characterized TQ-B3525 (dual PI3Kα/δ inhibitor) and assessed the recommended phase 2 dose (RP2D), safety, efficacy, and pharmacokinetics in relapsed or refractory (R/R) lymphoma or advanced solid tumors (STs).
METHODS
Oral TQ-B3525 was given at eight dose levels on a 28-day cycle. Primary end points were dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and safety.
RESULTS
TQ-B3525 showed high selectivity and suppressed tumor growth. Between June 12, 2018, and November 18, 2020, 80 patients were enrolled (63 in dose-escalation cohort; 17 in dose-expansion cohort). Two DLTs occurred in two (two of 63, 3.2%) DLT-evaluable patients; MTD was not identified. TQ-B3525 at 20 mg once daily was selected as RP2D. Grade 3 or worse treatment-related adverse events mainly included hyperglycemia (16.3%), neutrophil count decreased (15.0%), and diarrhea (10.0%). Two (2.5%) treatment-related deaths were reported. Sixty patients with R/R lymphoma and 11 advanced STs demonstrated objective response rates of 68.3% and 9.1%, disease control rates of 91.7% and 54.6%, median progression-free survivals of 12.1 and 1.1 months; median overall survivals were not reached.
CONCLUSION
TQ-B3525 exhibited rapid absorption and a nearly proportional increase in exposure. Acceptable safety and promising efficacy support further investigation of TQ-B3525 (20 mg once daily) for R/R lymphoma.
PubMed: 38926891
DOI: 10.1002/cncr.35453 -
Discovery Medicine Jun 2024Cigarette smoke (CS) induces autophagy and endoplasmic reticulum (ER) stress in the lungs. Research suggests that maternal exposure to CS during pregnancy leads to...
BACKGROUND
Cigarette smoke (CS) induces autophagy and endoplasmic reticulum (ER) stress in the lungs. Research suggests that maternal exposure to CS during pregnancy leads to decreased lung function in offspring. However, the effects of maternal CS exposure on lung autophagy and ER stress in offspring during pregnancy remain unclear.
METHODS
C57BL/6J female mice were divided into the AA (air treatment during both pre-pregnancy and pregnancy), AS (air treatment during pre-pregnancy and CS treatment during pregnancy), SA (CS treatment during pre-pregnancy and air treatment during pregnancy), and SS (CS treatment during both pre-pregnancy and pregnancy) groups. The male offspring mice were selected to the study and euthanized 49 days after birth for the study. Hematoxylin and eosin (HE) staining was employed to observe pathological alterations, while transmission electron microscopy (TEM) was utilized to examine ultrastructure and autophagic vesicles. Additionally, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method was applied to identify apoptosis in lung tissues. Immunofluorescence, Real-Time PCR, and Western Blot analyses were conducted to assess the expression of ER stress and autophagy-related markers in lung tissues.
RESULTS
The findings revealed that exposure to CS heightened the extent of pathological damage and the abundance of autophagosomes in the lungs of offspring mice. TUNEL results indicated an increased fluorescence intensity in the AS, SA and SS groups, with the most significant in AS and SS groups. Furthermore, CS exposure augmented the fluorescence intensity and expression of ER stress and autophagy-related proteins. The expression of C/EBP-homologous protein (CHOP) exhibited no discernible difference between the SA and SS groups but showed a significant increase in the AS group. Conversely, the expression levels of glucose-regulated protein 78 (GRP78), Caspase-12, Beclin-1, and microtubule-associated protein 1 light chain 3 (LC3) exhibited no significant difference between the AS and SA groups, whereas they were significantly upregulated in the SS group.
CONCLUSIONS
Preconceptional and gestational exposure to CS heightened ER stress and autophagy in the lungs of mouse offspring. However, in mothers who smoked, withdrawal from CS during pregnancy led to a reduction in ER stress and autophagy in the lungs of their offspring.
Topics: Animals; Endoplasmic Reticulum Stress; Autophagy; Female; Pregnancy; Mice; Lung; Mice, Inbred C57BL; Maternal Exposure; Male; Endoplasmic Reticulum Chaperone BiP; Prenatal Exposure Delayed Effects; Apoptosis; Tobacco Smoke Pollution
PubMed: 38926111
DOI: 10.24976/Discov.Med.202436185.115 -
Journal of Applied Microbiology Jun 2024This study aimed to assess the pharmacokinetic/pharmacodynamic (PK/PD) targets of danofloxacin to minimize the risk of selecting resistant P. multocida mutants and to...
AIMS
This study aimed to assess the pharmacokinetic/pharmacodynamic (PK/PD) targets of danofloxacin to minimize the risk of selecting resistant P. multocida mutants and to identify the mechanisms underlying their resistance in an in vitro dynamic model, attaining the optimum dosing regimen of danofloxacin to improve its clinical efficacy based on the mutant selection window (MSW) hypothesis.
METHODS AND RESULTS
Danofloxacin at seven dosing regimens and five days of treatment were simulated to quantify the bactericidal kinetics and enrichment of resistant mutants upon continuous antibiotic exposure. The magnitudes of PK/PD targets associated with different efficacies were determined in the model. The 24 h danofloxacin area under the concentration-time curve to MIC ratios (AUC24h/MIC) associated with bacteriostatic, bactericidal and eradication effects against P. multocida were 34, 52, and 64 h. This translates to average danofloxacin concentrations (Cav) over 24 h being 1.42, 2.17, and 2.67 times the MIC, respectively. An AUC/MIC-dependent antibacterial efficacy and AUC/MPC (mutant prevention concentration)-dependent enrichment of P. multocida mutants in which maximum losses in danofloxacin susceptibility occurred at a simulated AUC24h/MIC ratio of 72 h (i.e. Cav of 3 times the MIC). The overexpression of efflux pumps (acrAB-tolC) and their regulatory genes (marA, soxS, and ramA) was associated with reduced susceptibility in danofloxacin-exposed P. multocida. The AUC24h/MPC ratio of 19 h (i.e. Cav of 0.8 times the MPC) was determined to be the minimum mutant prevention target value for the selection of resistant P. multocida mutants.
CONCLUSIONS
The emergence of P. multocida resistance to danofloxacin exhibited a concentration-dependent pattern and was consistent with the MSW hypothesis. The current clinical dosing regimen of danofloxacin (2.5 mg kg-1) may have a risk of treatment failure due to inducible fluoroquinolone resistance.
PubMed: 38925653
DOI: 10.1093/jambio/lxae154