Molecular identification of Lodoicea maldivica (coco de mer) seeds

<p>Abstract</p> <p>Background</p> <p>The edible endosperm of <it>Lodoicea maldivica </it>with the common name of <it>coco de mer </it>is used in Chinese medicine for treating cough. Native to Seychelles, <it>Lodoicea maldivica </it>seeds have commanded high prices for centuries due to its scarcity. This study aims to develop a molecular identification method for the authentication of <it>Lodoicea maldivica </it>seeds.</p> <p>Methods</p> <p>DNA was extracted from the sample. Two polymerase chain reaction (PCR) systems were developed to amplify a region of the chloroplast DNA and the nuclear phosphoribulokinase (PRK) region specific to <it>Lodoicea maldivica </it>respectively. DNA sequence of a sample was determined and compared with that of the <it>Lodoicea maldivica </it>reference material.</p> <p>Results</p> <p>The PRK gene of <it>Lodoicea maldivica </it>was successfully amplified and sequenced for identification.</p> <p>Conclusion</p> <p>A new molecular method for the identification of <it>Lodoicea maldivica </it>seeds in fresh, frozen or dried forms was developed.</p

Immunoinformatic evaluation of multiple epitope ensembles as vaccine candidates:E coli 536

Epitope prediction is becoming a key tool for vaccine discovery. Prospective analysis of bacterial and viral genomes can identify antigenic epitopes encoded within individual genes that may act as effective vaccines against specific pathogens. Since B-cell epitope prediction remains unreliable, we concentrate on T-cell epitopes, peptides which bind with high affinity to Major Histacompatibility Complexes (MHC). In this report, we evaluate the veracity of identified T-cell epitope ensembles, as generated by a cascade of predictive algorithms (SignalP, Vaxijen, MHCPred, IDEB, EpiJen), as a candidate vaccine against the model pathogen uropathogenic gram negative bacteria Escherichia coli (E-coli) strain 536 (O6:K15:H31). An immunoinformatic approach was used to identify 23 epitopes within the E-coli proteome. These epitopes constitute the most promiscuous antigenic sequences that bind across more than one HLA allele with high affinity (IC50 <50nM). The reliability of software programmes used, polymorphic nature of genes encoding MHC and what this means for population coverage of this potential vaccine are discussed

Validation and application of health utilities index in Chinese subjects with down syndrome

Objectives: The objectives of the study were (1) to validate the Chinese version of Health Utilities Index (HUI-Ch); (2) to examine the Health-related Quality of Life (HRQoL) of Chinese subjects with Down syndrome (DS); and (3) to study the impact of chronic health conditions on HRQoL of Chinese with DS. Methods: The multiple choice questionnaire for scoring Health Utilities Index Mark 2 (HUI2) and Health Utilities Index Mark 3 (HUI3) was translated and validated. In addition to the HRQoL scores from HUI2 and HUI3, proxy-data on socio-demographics, and 10 common chronic health conditions for people with DS were collected and analyzed. Data analysis involves multiple imputation and multiple regression analysis to predict variations in HRQoL in relation to different factors. Lastly, a gradient interval was constructed on the number of chronic health conditions in relation to HRQoL. Results: HUI-Ch was validated according to standard guidelines. People with DS were found to have a lower HRQoL as compared to the general population, with the majority categorized as moderate or severe on the scale. Behavioral and hearing problems on HUI2, and hearing problems on HUI3 were found to be statistically significant predictors of a lower HRQoL score. A significant gradient relationship existed showing when the number of health problems increased, the HRQoL scores decreased. Conclusions: HUI-Ch is a valid instrument to assess HRQoL. It can have broad application in Chinese subjects with DS including the study of the impact of different chronic health conditions on their quality of life. The quantifiable nature of HUI-Ch will facilitate longitudinal study on the well-being of subjects with DS and evaluation of effectiveness of intervention programs in the near future

Effectiveness of BNT162b2 and CoronaVac vaccinations against SARS-CoV-2 omicron infection in people aged 60 years or above: a case–control study

BACKGROUND: In view of limited evidence that specifically addresses vaccine effectiveness (VE) in the older population, this study aims to evaluate the real-world effectiveness of BNT162b2 and CoronaVac in older adults during the Omicron BA.2 outbreak. METHODS: This case-control study analyzed data available between January and March 2022 from the electronic health databases in Hong Kong and enrolled individuals aged 60 or above. Each case was matched with up to 10 controls by age, sex, index date and Charlson Comorbidity Index for the four outcomes (COVID-19 infection, COVID-19-related hospitalization, severe complications, and all-cause mortality) independently. Conditional logistic regression was conducted to evaluate VE of BNT162b2 and CoronaVac against COVID-19-related outcomes within 28 days after COVID-19 infection among participants stratified by age groups (60-79, ≥80 years old). RESULTS: A dose-response relationship between the number of vaccine doses received and protection against severe or fatal disease was observed. Highest VE (95% CI) against COVID-19 infection was observed in individuals aged ≥80 who received three doses of BNT162b2 [75.5% (73.1-77.7%)] or three doses of CoronaVac [53.9% (51.0-56.5%)] compared to those in the younger age group who received three doses of BNT162b2 [51.1% (49.9-52.4%)] or three doses of CoronaVac [2.0% (-0.1-4.1%)]. VE (95% CI) was higher for other outcomes, reaching 91.9% (89.4-93.8%) and 86.7% (84.3-88.8%) against COVID-19-related hospitalization; 85.8% (61.2-94.8%) and 89.8% (72.4-96.3%) against COVID-19-related severe complications; and 96.4% (92.9-98.2%) and 95.0% (92.1-96.8%) against COVID-19-related mortality after three doses of BNT162b2 and CoronaVac in older vaccine recipients, respectively. A similar dose-response relationship was established in younger vaccine recipients and after stratification by sex and Charlson Comorbidity Index. CONCLUSION: Both BNT162b2 and CoronaVac vaccination were effective in protecting older adults against COVID-19 infection and COVID-19-related severe outcomes amidst the Omicron BA.2 pandemic, and VE increased further with the third dose

Waning effectiveness against COVID-19-related hospitalisation, severe complications, and mortality with two to three doses of CoronaVac and BNT162b2: a case-control study

BACKGROUND: This study aims to evaluate waning effectiveness against severe and fatal COVID-19 with 2-3 doses of CoronaVac/BNT162b2, where data is limited. METHODS: A case-control study included individuals aged ≥18 years, unvaccinated or received 2-3 doses of CoronaVac/BNT162b2, using electronic healthcare databases in Hong Kong. Those with first COVID-19-related hospitalisation, severe complications, or mortality between 1 January and 15 August 2022 were defined as cases and matched with up-to-10 controls by age, sex, index date, and Charlson Comorbidity Index. Vaccine effectiveness (VE) against COVID-19-related outcomes was estimated at different time intervals from second and third dose vaccination (0-13 up-to 210-240 days) using conditional logistic regression adjusted for comorbidities and medications. RESULTS: By 211-240 days after second dose, VE against COVID-19-related hospitalisation reduced to 46.6% (40.7%-51.8%) for BNT162b2 and 36.2% (28.0%-43.4%) for CoronaVac, and VE against COVID-19-related mortality were 73.8% (55.9%-84.4%) and 76.6% (60.8%-86.0%). After third dose, VE against COVID-19-related hospitalisation decreased from 91.2% (89.5%-92.6%) for BNT162b2 and 76.7% (73.7%-79.4%) for CoronaVac at 0-13 days, to 67.1% (60.4%-72.6%) and 51.3% (44.2%-57.5%) at 91-120 days. VE against COVID-19-related mortality for BNT162b2 remained high from 0-13 days [98.2% (95.0%-99.3%)] to 91-120 days [94.6% (77.7%-98.7%)], and for CoronaVac reduced from 0-13 days [96.7% (93.2%-98.4%)] to 91-120 days [86.4% (73.3%-93.1%)]. CONCLUSIONS: Significant risk reduction against COVID-19-related hospitalisation and mortality after CoronaVac or BNT162b2 vaccination was observed for >240 and >120 days after second and third dose compared to unvaccinated, despite significant waning over time. Timely administration of booster doses could provide higher levels of protection

Effectiveness of BNT162b2 and CoronaVac vaccinations against mortality and severe complications after SARS-CoV-2 Omicron BA.2 infection: a case–control study

Data regarding protection against mortality and severe complications after Omicron BA.2 infection with CoronaVac and BNT162b2 vaccines remains limited. We conducted a case–control study to evaluate the risk of severe complications and mortality following 1–3 doses of CoronaVac and BNT162b2 using electronic health records database. Cases were adults with their first COVID-19-related mortality or severe complications between 1 January and 31 March 2022, matched with up-to 10 controls by age, sex, index date, and Charlson Comorbidity Index. Vaccine effectiveness against COVID-19-related mortality and severe complications by type and number of doses was estimated using conditional logistic regression adjusted for comorbidities and medications. Vaccine effectiveness (95% CI) against COVID-19-related mortality after two doses of BNT162b2 and CoronaVac were 90.7% (88.6–92.3) and 74.8% (72.5–76.9) in those aged ≥65, 87.6% (81.4–91.8) and 80.7% (72.8–86.3) in those aged 50–64, 86.6% (71.0–93.8) and 82.7% (56.5–93.1) in those aged 18–50. Vaccine effectiveness against severe complications after two doses of BNT162b2 and CoronaVac were 82.1% (74.6–87.3) and 58.9% (50.3–66.1) in those aged ≥65, 83.0% (69.6–90.5) and 67.1% (47.1–79.6) in those aged 50–64, 78.3% (60.8–88.0) and 77.8% (49.6–90.2) in those aged 18–50. Further risk reduction with the third dose was observed especially in those aged ≥65 years, with vaccine effectiveness of 98.0% (96.5–98.9) for BNT162b2 and 95.5% (93.7–96.8) for CoronaVac against mortality, 90.8% (83.4–94.9) and 88.0% (80.8–92.5) against severe complications. Both CoronaVac and BNT162b2 vaccination were effective against COVID-19-related mortality and severe complications amidst the Omicron BA.2 pandemic, and risks decreased further with the third dose

Interleukin-10 Promoter Polymorphism is Associated with the Predisposition to the Development of IgA Nephropathy and Focal Segmental Glomerulosclerosis in Korea

The roles of interleukin-10 (IL-10) have been emphasized in several models of glomerulonephritis (GN). Three biallelic polymorphisms within the IL-10 promoter region, at positions -1,082, -819, and -592 from the transcription initiation site, were shown to affect the level of IL-10 production. To investigate the effect of IL-10 promoter polymorphisms on the predisposition to development of GN in Korea, IL-10 promoter polymorphisms were assayed by polymerase chain reaction followed by restriction fragment length polymorphism in 108 patients with IgA nephropathy (IgAN), 49 focal segmental glomerulosclerosis (FSGS), and 100 healthy controls. In comparison with the control, the frequency of -1,082*G alleles were lower in IgAN and the frequencies of -592*C and -819*C were lower in FSGS, respectively. As for the haplotype, GCC haplotype was less frequent among IgAN than the control and ATA haplotype was more frequent among FSGS than the control (p<0.05). The frequency of intermediate producer genotypes (GCC/ACC and GCC/ATA) were lower among IgAN or FSGS than the control. Our findings suggested that IL-10 promoter polymorphism predisposed to the development of IgAN and FSGS in Korean patients

Repurposing hyperpolarization-activated cyclic nucleotide-gated channels as a novel therapy for breast cancer.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are members of the voltage-gated cation channel family known to be expressed in the heart and central nervous system. Ivabradine, a small molecule HCN channel-blocker, is FDA-approved for clinical use as a heart rate-reducing agent. We found that HCN2 and HCN3 are overexpressed in breast cancer cells compared with normal breast epithelia, and the high expression of HCN2 and HCN3 is associated with poorer survival in breast cancer patients. Inhibition of HCN by Ivabradine or by RNAi, aborted breast cancer cell proliferation in vitro and suppressed tumour growth in patient-derived tumour xenograft models established from triple-negative breast cancer (TNBC) tissues, with no evident side-effects on the mice. Transcriptome-wide analysis showed enrichment for cholesterol metabolism and biosynthesis as well as lipid metabolism pathways associated with ER-stress following Ivabradine treatment. Mechanistic studies confirmed that HCN inhibition leads to ER-stress, in part due to disturbed Ca2+ homeostasis, which subsequently triggered the apoptosis cascade. More importantly, we investigated the synergistic effect of Ivabradine and paclitaxel on TNBC and confirmed that both drugs acted synergistically in vitro through ER-stress to amplify signals for caspase activation. Combination therapy could suppress tumour growth of xenografts at much lower doses for both drugs. In summary, our study identified a new molecular target with potential for being developed into targeted therapy, providing scientific grounds for initiating clinical trials for a new treatment regimen of combining HCN inhibition with chemotherapy

Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases