Displaying publications 21 - 40 of 57 in total

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  1. Antiproliferative effects of boswellic acid-loaded chitosan nanoparticles on human lung cancer cell line A549
    Solanki N, Mehta M, Chellappan DK, Gupta G, Hansbro NG, Tambuwala MM, et al.
    Future Med Chem, 2020 11;12(22):2019-2034.
    PMID: 33124483 DOI: 10.4155/fmc-2020-0083
    Aim: In the present study boswellic acids-loaded chitosan nanoparticles were synthesized using ionic gelation technique. The influence of independent variables were studied and optimized on dependent variables using central composite design. Methodology & results: The designed nanoparticles were observed spherical in shape with an average size of 67.5-187.2 nm and have also shown an excellent entrapment efficiency (80.06 ± 0.48). The cytotoxicity assay revealed enhanced cytotoxicity for drug-loaded nanoparticles in contrast to the free drug having an IC50 value of 17.29 and 29.59 μM, respectively. Flow cytometry confirmed that treatment of cells with 40 μg/ml had arrested 22.75 ± 0.3% at SubG0 phase of the cell cycle when compared with untreated A459 cells. The observed results justified the boswellic acids-loaded chitosan nanoparticles were effective due to greater cellular uptake, sustained intercellular drug retention and enhanced antiproliferative effect by inducing apoptosis.
  2. Biochar for cadmium pollution mitigation and stress resistance in tobacco growth
    Ren T, Chen N, Wan Mahari WA, Xu C, Feng H, Ji X, et al.
    Environ Res, 2021 01;192:110273.
    PMID: 33002505 DOI: 10.1016/j.envres.2020.110273
    Pot experiments were conducted to investigate the influence of biochar addition and the mechanisms that alleviate Cd stress in the growth of tobacco plant. Cadmium showed an inhibitory effect on tobacco growth at different post-transplantation times, and this increased with the increase in soil Cd concentration. The growth index decreased by more than 10%, and the photosynthetic pigment and photosynthetic characteristics of the tobacco leaf were significantly reduced, and the antioxidant enzyme activity was enhanced. Application of biochar effectively alleviated the inhibitory effect of Cd on tobacco growth, and the alleviation effect of treatments is more significant to the plants with a higher Cd concentration. The contents of chlorophyll a, chlorophyll b, and carotenoids in the leaves of tobacco plants treated with biochar increased by 9.99%, 12.58%, and 10.32%, respectively, after 60 days of transplantation. The photosynthetic characteristics index of the net photosynthetic rate increased by 11.48%, stomatal conductance increased by 11.44%, and intercellular carbon dioxide concentration decreased to 0.92. Based on the treatments, during the growth period, the antioxidant enzyme activities of tobacco leaves comprising catalase, peroxidase, superoxide dismutase, and malondialdehyde increased by 7.62%, 10.41%, 10.58%, and 12.57%, respectively, after the application of biochar. Our results show that biochar containing functional groups can effectively reduce the effect of Cd stress by intensifying the adsorption or passivation of Cd in the soil, thereby, significantly reducing the Cd content in plant leaves, and providing a theoretical basis and method to alleviate soil Cd pollution and effect soil remediation.
  3. Fulltext Concepts of advanced therapeutic delivery systems for the management of remodeling and inflammation in airway diseases
    Dhanjal DS, Sharma P, Mehta M, Tambuwala MM, Prasher P, Paudel KR, et al.
    Future Med Chem, 2022 Feb;14(4):271-288.
    PMID: 35019757 DOI: 10.4155/fmc-2021-0081
    Chronic respiratory disorders affect millions of people worldwide. Pathophysiological changes to the normal airway wall structure, including changes in the composition and organization of its cellular and molecular constituents, are referred to as airway remodeling. The inadequacy of effective treatment strategies and scarcity of novel therapies available for the treatment and management of chronic respiratory diseases have given rise to a serious impediment in the clinical management of such diseases. The progress made in advanced drug delivery, has offered additional advantages to fight against the emerging complications of airway remodeling. This review aims to address the gaps in current knowledge about airway remodeling, the relationships between remodeling, inflammation, clinical phenotypes and the significance of using novel drug delivery methods.
  4. Fulltext Toll-like receptor 2 and 4 have opposing roles in the pathogenesis of cigarette smoke-induced chronic obstructive pulmonary disease
    Haw TJ, Starkey MR, Pavlidis S, Fricker M, Arthurs AL, Nair PM, et al.
    Am. J. Physiol. Lung Cell Mol. Physiol., 2018 02 01;314(2):L298-L317.
    PMID: 29025711 DOI: 10.1152/ajplung.00154.2017
    Chronic obstructive pulmonary disease (COPD) is the third leading cause of morbidity and death and imposes major socioeconomic burdens globally. It is a progressive and disabling condition that severely impairs breathing and lung function. There is a lack of effective treatments for COPD, which is a direct consequence of the poor understanding of the underlying mechanisms involved in driving the pathogenesis of the disease. Toll-like receptor (TLR)2 and TLR4 are implicated in chronic respiratory diseases, including COPD, asthma and pulmonary fibrosis. However, their roles in the pathogenesis of COPD are controversial and conflicting evidence exists. In the current study, we investigated the role of TLR2 and TLR4 using a model of cigarette smoke (CS)-induced experimental COPD that recapitulates the hallmark features of human disease. TLR2, TLR4, and associated coreceptor mRNA expression was increased in the airways in both experimental and human COPD. Compared with wild-type (WT) mice, CS-induced pulmonary inflammation was unaltered in TLR2-deficient ( Tlr2-/-) and TLR4-deficient ( Tlr4-/-) mice. CS-induced airway fibrosis, characterized by increased collagen deposition around small airways, was not altered in Tlr2-/- mice but was attenuated in Tlr4-/- mice compared with CS-exposed WT controls. However, Tlr2-/- mice had increased CS-induced emphysema-like alveolar enlargement, apoptosis, and impaired lung function, while these features were reduced in Tlr4-/- mice compared with CS-exposed WT controls. Taken together, these data highlight the complex roles of TLRs in the pathogenesis of COPD and suggest that activation of TLR2 and/or inhibition of TLR4 may be novel therapeutic strategies for the treatment of COPD.
  5. Fulltext Breast milk from healthy women has higher anti-Candida properties than women with vaginal infections during pregnancy
    Nisaa AA, Oon CE, Sreenivasan S, Balakrishnan V, Tan JJ, Teh CS, et al.
    Food Sci Biotechnol, 2023 Mar;32(4):471-480.
    PMID: 36911325 DOI: 10.1007/s10068-022-01088-x
    The aim of this study was to investigate the different immunological and antimicrobial properties of breast milk from women with (W) or without (WO) vaginal yeast infections during pregnancy in 85 lactating women (W, n = 43; WO, n = 42). Concentrations of IL-10, IgA, IgM, IgG, EGF, and TGF-α were similar in both groups. However, breast milk of women aged below 31 years old from the W-group showed higher concentration of EGF than the WO-group (p = 0.031). Breast milk from WO-group exhibited higher anti-Candida properties than W-group, both via growth inhibition and aggregation of yeast cells (p 
  6. Fulltext Probiotic Improves Skin Oxidation, Elasticity, and Structural Properties in Aging Rats
    Lee BK, Xu P, Mageswaran UM, Jeong WS, Engku-Husna EI, Muhammad-Nashriq K, et al.
    Prev Nutr Food Sci, 2023 Sep 30;28(3):293-301.
    PMID: 37842246 DOI: 10.3746/pnf.2023.28.3.293
    Skin aging, which affects all living organisms, is associated with oxidative stress. Probiotics exhibit antioxidant properties by producing reactive metabolites that counter oxidative stress. We hypothesized that Limosilactobacillus fermentum USM 4189 (LF 4189) has antioxidative properties and may prevent skin aging. In the present study, we used a D-galactose senescence-induced rat model to evaluate the potential antioxidative capability of LF 4189. The results indicated that rats administered LF 4189 exhibited increased plasma antioxidative activity (P=0.004), lipid peroxidation capacity (P=0.007), and skin elasticity compared with untreated aged rats (P=0.005). LF 4189 prevented telomere length shortening (P<0.05), indicating the potential to prevent senescence. A higher apoptotic activity was observed in old rats compared with young rats, whereas LF 4189 reduced the expression of four antioxidative enzyme genes that function as radical scavengers (all P<0.05), suggesting that the LF 4189 group had a reduced need to scavenge free radicals. Our findings indicate the potential of probiotics, such as LF 4189, as an anti-aging dietary intervention with antioxidant potential to improve skin health.
  7. A novel Tembusu virus isolated from goslings in China form a new subgenotype 2.1.1
    Zhu Y, Hu Z, Lv X, Huang R, Gu X, Zhang C, et al.
    Transbound Emerg Dis, 2022 Jul;69(4):1782-1793.
    PMID: 33993639 DOI: 10.1111/tbed.14155
    Since 2010, several duck Tembusu viruses (DTMUVs) have been isolated from infected ducks in China, and these virus strains have undergone extensive variation over the years. Although the infection rate is high, the mortality rate is usually relatively low-~5%-30%; however, since fall 2019, an infectious disease similar to DTMUV infection but with a high mortality rate of ~50% in goslings has been prevalent in Anhui Province, China. The present study identified a new Tembusu virus, designated DTMUV/Goose/China/2019/AQ-19 (AQ-19), that is believed to be responsible for the noticeably high mortality in goslings. To investigate the genetic variation of this strain, its entire genome was sequenced and analysed for specific variations, and goslings and mice were challenged with the isolated virus to investigate its pathogenicity. The AQ-19 genome shared only 94.3%-96.9% and 90.9% nucleotide identity with other Chinese and Malaysian DTMUVs, respectively; however, AQ-19 has high homology with Thailand DTMUVs (97.2%-98.1% nucleotide identity). Phylogenetic analysis of the E gene revealed that AQ-19 and most of Thailand DTMUVs form a branch separate from any of the previously reported DTMUV strains in China. After the challenge, some goslings and mice showed typical clinical signs of DTMUV, particularly severe neurological dysfunction. AQ-19 has high virulence in goslings and mice, resulting in 60% and 70% mortality through intramuscular and intracerebral routes, respectively. Pathological examination revealed severe histological lesions in the brain and liver of the infected goslings and mice. Taken together, these results demonstrated the emergence of a novel Tembusu virus with high virulence circulating in goslings in China for the first time, and our findings highlight the high genetic diversity of DTMUVs in China. Further study of the pathogenicity and host range of this novel Tembusu virus is particularly important.
  8. Fulltext The Role of 1-Methylcyclopropene in the regulation of ethylene biosynthesis and ethylene receptor gene expression in Mangifera indica L. (Mango Fruit)
    Li L, Shuai L, Sun J, Li C, Yi P, Zhou Z, et al.
    Food Sci Nutr, 2020 Feb;8(2):1284-1294.
    PMID: 32148834 DOI: 10.1002/fsn3.1417
    Mango (Mangifera indica L.) is respiratory climacteric fruit that ripens and decomposes quickly following their harvest. 1-methylcyclopropene (1-MCP) is known to affect the ripening of fruit, delaying the decay of mango stored under ambient conditions. The objective of this study was to clarify the role of 1-MCP in the regulation of ethylene biosynthesis and ethylene receptor gene expression in mango. 1-MCP significantly inhibited the 1-aminocyclopropane-1-carboxylic acid (ACC) content. The activity of ACC oxidase (ACO) increased on days 6, 8, and 10 of storage, whereas delayed ACC synthase (ACS) activity increased after day 4. The two homologous ethylene receptor genes, ETR1 and ERS1 (i.e., MiETR1 and MiERS1), were obtained and deposited in GenBank® (National Center for Biotechnology Information-National Institutes of Health [NCBI-NIH]) (KY002681 and KY002682). The MiETR1 coding sequence was 2,220 bp and encoded 739 amino acids (aa). The MiERS1 coding sequence was 1,890 bp and encoded 629 aa, similar to ERS1 in other fruit. The tertiary structures of MiETR1 and MiERS1 were also predicted. MiERS1 lacks a receiver domain and shares a low homology with MiETR1 (44%). The expression of MiETR1 and MiERS1 mRNA was upregulated as the storage duration extended and reached the peak expression on day 6. Treatment with 1-MCP significantly reduced the expression of MiETR1 on days 4, 6, and 10 and inhibited the expression of MiETR1 on days 2, 4, 6, and 10. These results indicated that MiETR1 and MiERS1 had important functions in ethylene signal transduction. Treatment with 1-MCP might effectively prevent the biosynthesis of ethylene, as well as ethylene-induced ripening and senescence. This study presents an innovative method for prolonging the storage life of mango after their harvest through the regulation of MiETR1 and MiERS1 expression.
  9. Lactobacillus probiotics restore vaginal and gut microbiota of pregnant women with vaginal candidiasis
    Ang XY, Roslan NS, Ahmad N, Yusof SM, Abdullah N, Nik Ab Rahman NN, et al.
    Benef Microbes, 2023 Nov 23;14(5):421-431.
    PMID: 38350486 DOI: 10.1163/18762891-20220103
    The development of probiotics has now included the areas along the gut-vaginal axis. We thus aimed to investigate the effects of lactobacilli probiotic to modulate and restore vaginal and gut microbiota of pregnant women with vaginal candidiasis (VC). A randomised, double-blind and placebo-controlled study was performed in 78 pregnant women with VC. Patients were randomised to either the probiotic (SynForU-HerCare) or placebo which were administered at baseline and continued for 8-weeks (two capsules/day of 9.5 log cfu/capsule). Microbiota profiles were assessed at time points of weeks-0, 4 and 8 for high vaginal swab and faecal samples. Shannon diversity index showed that after 8-weeks amid VC, a shift in microbial community compositional changes occurred in the high vaginal region at both genus (P=0.025) and species (P=0.044) levels, where the administration of probiotic prevented such a shift. These changes were mainly attributed to a decreased in abundance of Lactobacillus (P=0.042) accompanied by increased abundance of Prevotella (P=0.002) and Atopobium (P=0.002) in the placebo group while the probiotic group remained unchanged over time. The administration of probiotics also prevented a reduced abundance of faecal phylum Firmicutes after 8-weeks as seen in the placebo group (P<0.0001), which also showed reduction at subsequent taxonomic levels of class, family, genera and species. VC has not only altered the microbiota of vagina regions but also gut microbiota profiles, causing lessening of gut microbiota that are crucial for gut nutrient availability, protection and immunity. The administration of lactobacilli probiotics has prevented such a shift, leading to better modulated gut and vaginal microenvironment amid VC. The study was registered at ClinicalTrials.gov: identifier number NCT03940612.
  10. Fulltext Constipation anti-aging effects by dairy-based lactic acid bacteria
    Jaafar MH, Xu P, Mageswaran UM, Balasubramaniam SD, Solayappan M, Woon JJ, et al.
    J Anim Sci Technol, 2024 Jan;66(1):178-203.
    PMID: 38618031 DOI: 10.5187/jast.2023.e93
    Constipation, which refers to difficulties in defecation and infrequent bowel movement in emptying the gastrointestinal system that ultimately produces hardened fecal matters, is a health concern in livestock and aging animals. The present study aimed to evaluate the potential effects of dairy-isolated lactic acid bacteria (LAB) strains to alleviate constipation as an alternative therapeutic intervention for constipation treatment in the aging model. Rats were aged via daily subcutaneous injection of D-galactose (600 mg/body weight [kg]), prior to induction of constipation via oral administration of loperamide hydrochloride (5 mg/body weight [kg]). LAB strains (L. fermentum USM 4189 or L. plantarum USM 4187) were administered daily via oral gavage (1 × 10 Log CFU/day) while the control group received sterile saline. Aged rats as shown with shorter telomere lengths exhibited increased fecal bulk and soften fecal upon administration of LAB strains amid constipation as observed using the Bristol Stool Chart, accompanied by a higher fecal moisture content as compared to the control (p < 0.05). Fecal water-soluble metabolite profiles showed a reduced concentration of threonine upon administration of LAB strains compared to the control (p < 0.05). Histopathological analysis also showed that the administration of LAB strains contributed to a higher colonic goblet cell count as compared to the control (p < 0.05). The present study illustrates the potential of dairy-sourced LAB strains as probiotics to ameliorate the adverse effect of constipation amid aging, and as a potential dietary intervention strategy for dairy foods including yogurt and cheese.
  11. Rutin loaded liquid crystalline nanoparticles inhibit non-small cell lung cancer proliferation and migration in vitro
    Paudel KR, Wadhwa R, Tew XN, Lau NJX, Madheswaran T, Panneerselvam J, et al.
    Life Sci, 2021 Jul 01;276:119436.
    PMID: 33789146 DOI: 10.1016/j.lfs.2021.119436
    Non-small cell lung cancer (NSCLC) is one of the major causes of cancer-related mortality globally. Despite the availability of therapeutic options, the improvement in patient survival is yet to be achieved. Recent advances in natural product (e.g., Rutin) research, therapeutic nanotechnology and especially the combination of both could aid in achieving significant improvements in the treatment or management of NSCLC. In this study, we explore the anti-cancer activity of Rutin-loaded liquid crystalline nanoparticles (LCNs) in an in vitro model where we have employed the A549 human lung epithelial carcinoma cell line. The anti-proliferative activity was determined by MTT and Trypan blue assays, whereas, the anti-migratory activity was evaluated by the scratch wound healing assay and a modified Boyden chamber assay. We also evaluated the anti-apoptotic activity by Annexin V-FITC staining, and the colony formation activity was studied using crystal violet staining. Here, we report that Rutin-LCNs showed promising anti-proliferative and anti-migratory activities. Furthermore, Rutin-LCNs also induced apoptosis in the A549 cells and inhibited colony formation. The findings warrant further detailed and in-depth anti-cancer mechanistic studies of Rutin-LCNs with a focus towards a potential therapeutic option for NSCLC. LCNs may help to enhance the solubility of Rutin used in the treatment of lung cancer and hence enhance the anticancer effect of Rutin.
  12. Fulltext Validation Study of Rajasekaran's Kyphosis Classification System: Do We Clearly Understand Single- and Two-Column Deficiencies?
    Shetty AP, Rajavelu R, Viswanathan VK, Watanabe K, Chhabra HS, Kanna RM, et al.
    Asian Spine J, 2020 Aug;14(4):475-488.
    PMID: 32493003 DOI: 10.31616/asj.2020.0014
    STUDY DESIGN: Multicenter validation study.

    PURPOSE: To evaluate the inter-rater reliability of Rajasekaran's kyphosis classification through a multicenter validation study.

    OVERVIEW OF LITERATURE: The classification of kyphosis, developed by Rajasekaran, incorporates factors related to curve characteristics, including column deficiency, disc mobility, curve magnitude, and osteotomy requirements. Although the classification offers significant benefits in determining prognosis and management decisions, it has not been subjected to multicenter validation.

    METHODS: A total of 30 sets of images, including plain radiographs, computed tomography scans, and magnetic resonance imaging scans, were randomly selected from our hospital patient database. All patients had undergone deformity correction surgery for kyphosis. Twelve spine surgeons from the Asia-Pacific region (six different countries) independently evaluated and classified the deformity types and proposed their surgical recommendations. This information was then compared with standard deformity classification and surgical recommendations.

    RESULTS: The kappa coefficients for the classification were as follows: 0.88 for type 1A, 0.78 for type 1B, 0.50 for type 2B, 0.40 for type 3A, 0.63 for type 3B, and 0.86 for type 3C deformities. The overall kappa coefficient for the classification was 0.68. Regarding the repeatability of osteotomy recommendations, kappa values were the highest for Ponte's (Schwab type 2) osteotomy (kappa 0.8). Kappa values for other osteotomy recommendations were 0.52 for pedicle subtraction/disc-bone osteotomy (Schwab type 3/4), 0.42 for vertebral column resection (VCR, type 5), and 0.30 for multilevel VCRs (type 6).

    CONCLUSIONS: Excellent accuracy was found for types 1A, 1B, and 3C deformities (ends of spectrum). There was more variation among surgeons in differentiating between one-column (types 2A and 2B) and two-column (types 3A and 3B) deficiencies, as surgeons often failed to recognize the radiological signs of posterior column failure. This failure to identify column deficiencies can potentially alter kyphosis management. There was excellent consensus among surgeons in the recommendation of type 2 osteotomy; however, some variation was observed in their choice for other osteotomies.

  13. Fulltext A pathogenic role for tumor necrosis factor-related apoptosis-inducing ligand in chronic obstructive pulmonary disease
    Haw TJ, Starkey MR, Nair PM, Pavlidis S, Liu G, Nguyen DH, et al.
    Mucosal Immunol, 2016 Jul;9(4):859-72.
    PMID: 26555706 DOI: 10.1038/mi.2015.111
    Chronic obstructive pulmonary disease (COPD) is a life-threatening inflammatory respiratory disorder, often induced by cigarette smoke (CS) exposure. The development of effective therapies is impaired by a lack of understanding of the underlining mechanisms. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine with inflammatory and apoptotic properties. We interrogated a mouse model of CS-induced experimental COPD and human tissues to identify a novel role for TRAIL in COPD pathogenesis. CS exposure of wild-type mice increased TRAIL and its receptor messenger RNA (mRNA) expression and protein levels, as well as the number of TRAIL(+)CD11b(+) monocytes in the lung. TRAIL and its receptor mRNA were also increased in human COPD. CS-exposed TRAIL-deficient mice had decreased pulmonary inflammation, pro-inflammatory mediators, emphysema-like alveolar enlargement, and improved lung function. TRAIL-deficient mice also developed spontaneous small airway changes with increased epithelial cell thickness and collagen deposition, independent of CS exposure. Importantly, therapeutic neutralization of TRAIL, after the establishment of early-stage experimental COPD, reduced pulmonary inflammation, emphysema-like alveolar enlargement, and small airway changes. These data provide further evidence for TRAIL being a pivotal inflammatory factor in respiratory diseases, and the first preclinical evidence to suggest that therapeutic agents that target TRAIL may be effective in COPD therapy.
  14. Spatiotemporal Dynamics of Coastal Viral Community Structure and Potential Biogeochemical Roles Affected by an Ulva prolifera Green Tide
    Han M, Sun J, Yang Q, Liang Y, Jiang Y, Gao C, et al.
    mSystems, 2023 Feb 23.
    PMID: 36815859 DOI: 10.1128/msystems.01211-22
    The world's largest macroalgal green tide, caused by Ulva prolifera, has resulted in serious consequences for coastal waters of the Yellow Sea, China. Although viruses are considered to be one of the key factors in controlling microalgal bloom demise, understanding of the relationship between viral communities and the macroalgal green tide is still poor. Here, a Qingdao coastal virome (QDCV) time-series data set was constructed based on the metagenomic analysis of 17 DNA viromes along three coastal stations of the Yellow Sea, covering different stages of the green tide from Julian days 165 to 271. A total of 40,076 viral contigs were detected and clustered into 28,058 viral operational taxonomic units (vOTUs). About 84% of the vOTUs could not be classified, and 62% separated from vOTUs in other ecosystems. Green tides significantly influenced the spatiotemporal dynamics of the viral community structure, diversity, and potential functions. For the classified vOTUs, the relative abundance of Pelagibacter phages declined with the arrival of the bloom and rebounded after the bloom, while Synechococcus and Roseobacter phages increased, although with a time lag from the peak of their hosts. More than 80% of the vOTUs reached peaks in abundance at different specific stages, and the viral peaks were correlated with specific hosts at different stages of the green tide. Most of the viral auxiliary metabolic genes (AMGs) were associated with carbon and sulfur metabolism and showed spatiotemporal dynamics relating to the degradation of the large amount of organic matter released by the green tide. IMPORTANCE To the best of our knowledge, this study is the first to investigate the responses of viruses to the world's largest macroalgal green tide. It revealed the spatiotemporal dynamics of the unique viral assemblages and auxiliary metabolic genes (AMGs) following the variation and degradation of Ulva prolifera. These findings demonstrate a tight coupling between viral assemblages, and prokaryotic and eukaryotic abundances were influenced by the green tide.
  15. Fulltext Vaginal Infections during Pregnancy Increase Breast Milk Microbiome Alpha Diversity and Alter Taxonomic Composition
    Nisaa AA, Oon CE, Sreenivasan S, Balakrishnan V, Rajendran D, Tan JJ, et al.
    Prev Nutr Food Sci, 2023 Mar 31;28(1):1-9.
    PMID: 37066035 DOI: 10.3746/pnf.2023.28.1.1
    We previously reported that breast milk from women with (W) or without (WO) vaginal yeast infection during pregnancy differs in its immunological and antimicrobial properties, especially against pathogenic vaginal Candida sp.. Here, we investigated the differences in microbiota profiles of breast milk from these groups. Seventy-two breast milk samples were collected from lactating mothers (W, n=37; WO, n=35). The DNA of bacteria was extracted from each breast milk sample for microbiota profiling by 16S rRNA gene sequencing. Breast milk from the W-group exhibited higher alpha diversity than that from the WO-group across different taxonomic levels of class (P=0.015), order (P=0.011), family (P=0.020), and genus (P=0.030). Compositional differences between groups as determined via beta diversity showed marginal differences at taxonomic levels of phylum (P=0.087), family (P=0.064), and genus (P=0.067). The W-group showed higher abundances of families Moraxellaceae (P=0.010) and Xanthomonadaceae (P=0.008), and their genera Acinetobacter (P=0.015), Enhydrobacter (P=0.015), and Stenotrophomonas (P=0.007). Meanwhile, the WO-group showed higher abundances of genus Staphylococcus (P=0.046) and species Streptococcus infantis (P=0.025). This study shows that, although breast milk composition is affected by vaginal infection during pregnancy, this may not pose a threat to infant growth and development.
  16. Fulltext Nutraceuticals and mitochondrial oxidative stress: bridging the gap in the management of bronchial asthma
    Allam VSRR, Paudel KR, Gupta G, Singh SK, Vishwas S, Gulati M, et al.
    Environ Sci Pollut Res Int, 2022 Sep;29(42):62733-62754.
    PMID: 35796922 DOI: 10.1007/s11356-022-21454-w
    Asthma is a chronic inflammatory disease primarily characterized by inflammation and reversible bronchoconstriction. It is currently one of the leading causes of morbidity and mortality in the world. Oxidative stress further complicates the pathology of the disease. The current treatment strategies for asthma mainly involve the use of anti-inflammatory agents and bronchodilators. However, long-term usage of such medications is associated with severe adverse effects and complications. Hence, there is an urgent need to develop newer, novel, and safe treatment modalities for the management of asthma. This has therefore prompted further investigations and detailed research to identify and develop novel therapeutic interventions from potent untapped resources. This review focuses on the significance of oxidative stressors that are primarily derived from both mitochondrial and non-mitochondrial sources in initiating the clinical features of asthma. The review also discusses the biological scavenging system of the body and factors that may lead to its malfunction which could result in altered states. Furthermore, the review provides a detailed insight into the therapeutic role of nutraceuticals as an effective strategy to attenuate the deleterious effects of oxidative stress and may be used in the mitigation of the cardinal features of bronchial asthma.
  17. Berberine-loaded engineered nanoparticles attenuate TGF-β-induced remodelling in human bronchial epithelial cells
    De Rubis G, Paudel KR, Liu G, Agarwal V, MacLoughlin R, de Jesus Andreoli Pinto T, et al.
    Toxicol In Vitro, 2023 Oct;92:105660.
    PMID: 37591407 DOI: 10.1016/j.tiv.2023.105660
    Airway remodelling occurs in chronic respiratory diseases (CRDs) such as asthma and chronic obstructive pulmonary disease (COPD). It is characterized by aberrant activation of epithelial reparation, excessive extracellular matrix (ECM) deposition, epithelial-to-mesenchymal transition (EMT), and airway obstruction. The master regulator is Transforming Growth Factor-β (TGF-β), which activates tissue repair, release of growth factors, EMT, increased cell proliferation, and reduced nitric oxide (NO) secretion. Due to its fundamental role in remodelling, TGF-β is an emerging target in the treatment of CRDs. Berberine is a benzylisoquinoline alkaloid with antioxidant, anti-inflammatory, and anti-fibrotic activities whose clinical application is hampered by poor permeability. To overcome these limitations, in this study, berberine was encapsulated in monoolein-based liquid crystalline nanoparticles (BM-LCNs). The potential of BM-LCNs in inhibiting TGF-β-induced remodelling features in human bronchial epithelial cells (BEAS-2B) was tested. BM-LCNs significantly inhibited TGF-β-induced migration, reducing the levels of proteins upregulated by TGF-β including endoglin, thrombospondin-1, basic fibroblast growth factor, vascular-endothelial growth factor, and myeloperoxidase, and increasing the levels of cystatin C, a protein whose expression was downregulated by TGF-β. Furthermore, BM-LCNs restored baseline NO levels downregulated by TGF-β. The results prove the in vitro therapeutic efficacy of BM-LCNs in counteracting TGF-β-induced remodelling features. This study supports the suitability of berberine-loaded drug delivery systems to counteract airway remodelling, with potential application as a treatment strategy against CRDs.
  18. Fulltext TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase
    Liu G, Haw TJ, Starkey MR, Philp AM, Pavlidis S, Nalkurthi C, et al.
    Nat Commun, 2023 Nov 14;14(1):7349.
    PMID: 37963864 DOI: 10.1038/s41467-023-42913-z
    Toll-like receptor 7 (TLR7) is known for eliciting immunity against single-stranded RNA viruses, and is increased in both human and cigarette smoke (CS)-induced, experimental chronic obstructive pulmonary disease (COPD). Here we show that the severity of CS-induced emphysema and COPD is reduced in TLR7-deficient mice, while inhalation of imiquimod, a TLR7-agonist, induces emphysema without CS exposure. This imiquimod-induced emphysema is reduced in mice deficient in mast cell protease-6, or when wild-type mice are treated with the mast cell stabilizer, cromolyn. Furthermore, therapeutic treatment with anti-TLR7 monoclonal antibody suppresses CS-induced emphysema, experimental COPD and accumulation of pulmonary mast cells in mice. Lastly, TLR7 mRNA is increased in pre-existing datasets from patients with COPD, while TLR7+ mast cells are increased in COPD lungs and associated with severity of COPD. Our results thus support roles for TLR7 in mediating emphysema and COPD through mast cell activity, and may implicate TLR7 as a potential therapeutic target.
  19. Fulltext Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer
    Lesseur C, Diergaarde B, Olshan AF, Wünsch-Filho V, Ness AR, Liu G, et al.
    Nat Genet, 2016 Dec;48(12):1544-1550.
    PMID: 27749845 DOI: 10.1038/ng.3685
    We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10-8), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10-9). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10-6) than in HPV-negative (OR = 0.75, P = 0.16) cancers.
  20. Fulltext Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci
    Kachuri L, Amos CI, McKay JD, Johansson M, Vineis P, Bueno-de-Mesquita HB, et al.
    Carcinogenesis, 2016 Jan;37(1):96-105.
    PMID: 26590902 DOI: 10.1093/carcin/bgv165
    Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000×) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73×10(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64×10(-6)), rs112290073 (OR = 1.85, P = 1.27×10(-5)), rs138895564 (OR = 2.16, P = 2.06×10(-5); among young cases, OR = 3.77, P = 8.41×10(-4)). In addition, we found that rs139852726 (P = 1.44×10(-3)) was associated with telomere length in a sample of 922 healthy individuals. The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.84×10(-7)) and lung cancer (P = 2.37×10(-5)) risk. In this largest fine-mapping study to investigate a large number of rare and novel variants within 5p15.33, we identified novel lung and adenocarcinoma susceptibility loci with large effects and provided support for the role of telomere length as the potential underlying mechanism.
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