Enterotoxigenic methicillin resistant Staphylococcus aureus contamination in salted fish from Gwadar Balochistan

Staphylococcus aureus is an important foodborne pathogen associated to food intoxication and other multiple infections in human being. Its presence in salted food is a serious issue due to its salt tolerance potential. A study was conducted to analyze the presence of enterotoxins producing drug resistance S. aureus in salted sea fish from Gwadar. Freshly persevered samples (n=50) of salted fish were subjected to analyze the presence of S. aureus using 16S rRNA and Nuc genes primers. The isolates were then evaluated for drug resistance and enterotoxins producing potential using specific primers for MecA (methicillin resistance gene), (SEA) staphylococcal enterotoxin A and (SEB) staphylococcal enterotoxin B genes. Total 13/50 (26%) of the samples were found positive for the presence of S. aureus, preliminary confirmed with biochemical profiling and finally with the help of target genes presence. The isolates were found showing 100% resistant to methicillin, which were molecularly confirmed by the presence of MecA gene present in genome. The isolates 5/13 (38%) were positive for SEA and 3/13 (23%) for SEB genes, whereas 2/13 (15%) were confirmed having both SEA and SEB genes in its genome. It was also confirmed that all the isolates were capable to form biofilm over the glass surfaces. It was concluded that the study confirmed the presence of enterotoxigenic methicillin resistance Staphylococcus aurous (MRSA) in salted fish product, that poses gross food safety concern. Preventive and control measures are necessary to handle this serious food safety concern.

The Effect of Nano Albumin Combined with Paclitaxel on Drug Resistance of Breast Cancer Through Regulating ATP Binding Cassette Subfamily B Member 1 (ABCB1)

The paclitaxel is a common-used chemotherapy drug and its combination with nano albumin reduces drug side effect. However, whether nab-paclitaxel affects drug resistance of breast cancer remains unclear. This study intends to discuss the mechanism of drug resistance induced by nab-paclitaxel. The drug resistance of MCF-7/nab-paclitaxel in MCF-7 cell and cell proliferation was detected by MTT along with analysis of ABCB1 expression, cell cycle, and apoptosis. There was stronger drug resistance of nab-paclitaxel in the MCF-7/nab-paclitaxel cell group through be adopted with different concentration of nab-paclitaxel at the 0th hour, 24th hour and 48th hour. There was remarkable abnormal expression of the ABCB1 in the MCF-7/nab-paclitaxel cell group. The si-ABCB1 could release the quantity of the MCF-7/nab-paclitaxel cell blocked at S period. And the si-ABCB1 could reduce the expression of cyclin D1 and CDK2 in the MCF-7/nab-paclitaxel cell notably. But the expression level of p21 was increased when there was high concentration of si-ABCB1. The si-ABCB1 could increase the quantity of the MCF-7/nab-paclitaxel cell at the later period of cell apoptosis notably. The rat’s tumor growth was delayed obviously at the MCF-7/nabpaclitaxel cell group treated by si-ABCB1. But the inhibiting effect of the MCF-7/nab-paclitaxel cell on tumor growth was less. There was stronger drug resistance of cell for the nano albumin combined with paclitaxel. The function of cell proliferation in breast cancer was restrained by the nano albumin combined with paclitaxel mainly through inducing the expression of ABCB1, adjusting the growth of cell cycle and the expression of P21/BCL-2 protein.

Epithelial-mesenchymal transition and H2O2 signaling – a driver of disease progression and a vulnerability in cancers

Mutation-selective drugs constitute a great advancement in personalized anticancer treatment with increased quality of life and overall survival in cancers. However, the high adaptability and evasiveness of cancers can lead to disease progression and the development of drug resistance, which cause recurrence and metastasis. A common characteristic in advanced neoplastic cancers is the epithelial-mesenchymal transition (EMT) which is strongly interconnected with H2O2 signaling, increased motility and invasiveness. H2O2 relays its signal through the installation of oxidative posttranslational modifications on cysteines. The increased H2O2 levels that are associated with an EMT confer a heightened sensitivity towards the induction of ferroptosis as a recently discovered vulnerability.

Molecular identification and anti-malarial drug resistance profile of Plasmodium falciparum from patients attending Kisoro Hospital, southwestern Uganda

Background The evolution of malaria infection has necessitated the development of highly sensitive diagnostic assays, as well as the use of dried blood spots (DBS) as a potential source of deoxyribonucleic acid (DNA) yield for polymerase chain reaction (PCR) assays. This study identified the different Plasmodium species in malaria-positive patients, and the anti-malarial drug resistance profile for Plasmodium falciparum using DBS samples collected from patients attending Kisoro Hospital in Kisoro district, Southwestern Uganda. Methods The blood samples were prospectively collected from patients diagnosed with malaria to make DBS, which were then used to extract DNA for real-time PCR and high-resolution melting (HRM) analysis. Plasmodium species were identified by comparing the control and test samples using HRM-PCR derivative curves. Plasmodium falciparum chloroquine (CQ) resistance transporter (pfcrt) and kelch13 to screen the samples for anti-malarial resistance markers. The HRM-PCR derivative curve was used to present a summary distribution of the different Plasmodium species as well as the anti-malarial drug profile. Results Of the 152 participants sampled, 98 (64.5%) were females. The average age of the participants was 34.9 years (range: 2 months–81 years). There were 134 samples that showed PCR amplification, confirming the species as Plasmodium. Plasmodium falciparum (N = 122), Plasmodium malariae (N = 6), Plasmodium ovale (N = 4), and Plasmodium vivax (N = 2) were the various Plasmodium species and their proportions. The results showed that 87 (71.3%) of the samples were sensitive strains/wild type (CVMNK), 4 (3.3%) were resistant haplotypes (SVMNT), and 31 (25.4%) were resistant haplotypes (CVIET). Kelch13 C580Y mutation was not detected. Conclusion The community served by Kisoro hospital has a high Plasmodium species burden, according to this study. Plasmodium falciparum was the dominant species, and it has shown that resistance to chloroquine is decreasing in the region. Based on this, molecular identification of Plasmodium species is critical for better clinical management. Besides, DBS is an appropriate medium for DNA preservation and storage for future epidemiological studies.

Computer-Assisted Discovery of Alkaloids with Schistosomicidal Activity

Schistosomiasis is a chronic parasitic disease caused by trematodes of the genus Schistosoma; it is commonly caused by Schistosoma mansoni, which is transmitted by Bioamphalaria snails. Studies show that more than 200 million people are infected and that more than 90% of them live in Africa. Treatment with praziquantel has the best cost–benefit result on the market. However, hypersensitivity, allergy, and drug resistance are frequently presented after administration. From this perspective, ligand-based and structure-based virtual screening (VS) techniques were combined to select potentially active alkaloids against S. mansoni from an internal dataset (SistematX). A set of molecules with known activity against S. mansoni was selected from the ChEMBL database to create two different models with accuracy greater than 84%, enabling ligand-based VS of the alkaloid bank. Subsequently, structure-based VS was performed through molecular docking using four targets of the parasite. Finally, five consensus hits (i.e., five alkaloids with schistosomicidal potential), were selected. In addition, in silico evaluations of the metabolism, toxicity, and drug-like profile of these five selected alkaloids were carried out. Two of them, namely, 11,12-methylethylenedioxypropoxy and methyl-3-oxo-12-methoxy-n(1)-decarbomethoxy-14,15-didehydrochanofruticosinate, had plausible toxicity, metabolomics, and toxicity profiles. These two alkaloids could serve as starting points for the development of new schistosomicidal compounds based on natural products.

Evaluation of a parasite-density based pooled targeted amplicon deep sequencing (TADS) method for molecular surveillance of Plasmodium falciparum drug resistance genes in Haiti

Sequencing large numbers of individual samples is often needed for countrywide antimalarial drug resistance surveillance. Pooling DNA from several individual samples is an alternative cost and time saving approach for providing allele frequency (AF) estimates at a population level. Using 100 individual patient DNA samples of dried blood spots from a 2017 nationwide drug resistance surveillance study in Haiti, we compared codon coverage of drug resistance-conferring mutations in four Plasmodium falciparum genes (crt, dhps, dhfr, and mdr1), for the same deep sequenced samples run individually and pooled. Samples with similar real-time PCR cycle threshold (Ct) values (+/- 1.0 Ct value) were combined with ten samples per pool. The sequencing success for samples in pools were higher at a lower parasite density than the individual samples sequence method. The median codon coverage for drug resistance-associated mutations in all four genes were greater than 3-fold higher in the pooled samples than in individual samples. The overall codon coverage distribution for pooled samples was wider than the individual samples. The sample pools with < 40 parasites/μL blood showed more discordance in AF calls for dhfr and mdr1 between the individual and pooled samples. This discordance in AF estimation may be due to low amounts of parasite DNA, which could lead to variable PCR amplification efficiencies. Grouping samples with an estimated ≥ 40 parasites/μL blood prior to pooling and deep sequencing yielded the expected population level AF. Pooling DNA samples based on estimates of > 40 parasites/μL prior to deep sequencing can be used for rapid genotyping of a large number of samples for these four genes and possibly other drug resistant markers in population-based studies. As Haiti is a low malaria transmission country with very few mixed infections and continued chloroquine sensitivity, the pooled sequencing approach can be used for routine national molecular surveillance of resistant parasites.

Extracellular Vesicles as Mediators of Therapy Resistance in the Breast Cancer Microenvironment

Resistance to various therapies, including novel immunotherapies, poses a major challenge in the management of breast cancer and is the leading cause of treatment failure. Bidirectional communication between breast cancer cells and the tumour microenvironment is now known to be an important contributor to therapy resistance. Several studies have demonstrated that crosstalk with the tumour microenvironment through extracellular vesicles is an important mechanism employed by cancer cells that leads to drug resistance via changes in protein, lipid and nucleic acid cargoes. Moreover, the cargo content enables extracellular vesicles to be used as effective biomarkers for predicting response to treatments and as potential therapeutic targets. This review summarises the literature to date regarding the role of extracellular vesicles in promoting therapy resistance in breast cancer through communication with the tumour microenvironment.

The Establisment of Caring Community Through TB Care Muhammadiyah at Puskesmas Tamansari Tasikmalaya City

Tuberculosis is an infectious disease whose number is still increasing in Indonesia, especially in Mulyasari Village, Tamansari District, Tasikmalaya City. TB incidence in Tamansari as of November 2020 reached 58 people, 3 people died and 1 person experienced drug resistance. Muhammadiyah is an Islamic da'wah movement for amar ma'ruf nahi munkar whose one of its da'wah movements is concerned with social humanitarian movements in the health sector. One of the health services that continues to be developed by Muhammadiyah is service and counseling to the community about TB disease and socialization of the use of TB Comprehensive PMO guidelines which can improve the cognitive, affective and psychomotor abilities of TB PMO which have an impact on increasing public awareness of TB disease. This program is implemented through counseling to cadres, religious leaders and PMOs in the work area of ??the Tamansari Health Center about TB disease and socialization of the use of TB Comprehensive PMO guidelines. Tamansari Health Center consists of 4 sub-districts, namely Mulyasari village, Sukahurip village, Setyawargi village and Setyamulya village. The results of this community service are an increase in the knowledge of cadres, PMOs and religious leaders about TB control and the formation of the TB Care Muhammadiyah management where in each disctrict there are 4 Muhammadiyah branch managers who collaborate with the village cadre coordinator to participate in monitoring the treatment of TB patients in the Tamansari area.