In vitro expression of secondary antitumor immunity by in vivo tumor-sensitized T cells: Inhibition by tumor-induced suppressor T cells

Summary In vitro cultivation of memory immune cells from P815- or P388-immune mice with corresponding irradiated tumor cells induced generation of cytolytic T cells (CTL). The induction of CTL generation, as well as the cytolytic activity itself, was tumor-specific. The in vitro generation of CTL from P815- or P388-immune cells was suppressed by spleen cells from mice bearing corresponding progressive tumors (tumor size 15 mm). The tumor-induced suppressor cells suppressed the in vitro generation of CTL, but did not affect their cytolytic function. The suppression was tumor-specific and was mediated by Ly1⁺2^–L3T4⁺ T cells. Treatment of suppressor cell donors with cyclophosphamide or sublethal -radiation completely abolished the ability of their spleen cells to inhibit the in vitro CTL generation.     

Silencing of the MEG3 gene promoted anti-cancer activity and drug sensitivity in glioma

Aberrant expression of MEG3 has been shown in various cancers. The purpose of this study is to evaluate the effect of MEG3 on glioma cells and the use of potential chemotherapeutics in glioma by modulating MEG3 expression. Cell viability, migration and chemosensitivity were assayed. Cell death was evaluated in MEG3 overexpressing and MEG3 suppressed cells. MEG3 expression was compared in patient-derived glioma cells concerning IDH1 mutation and WHO grades. Silencing of MEG3 inhibited cell proliferation and reduced cell migration while overexpression of MEG3 promoted proliferation in glioma cells. MEG3 inhibition improved the chemosensitivity of glioma cells to 5-fluorouracil (5FU) but not to navitoclax. On the other hand, there is no significant effect of MEG3 expression on temozolamide (TMZ) treatment which is a standard chemotherapeutic agent in glioma. Suppression of the MEG3 gene in patient-derived oligodendroglioma cells also showed the same effect whereas glioblastoma cell proliferation and chemosensitivity were not affected by MEG3 inhibition. Further, as a possible cell death mechanism of action apoptosis was investigated. Although MEG3 is a widely known tumour suppressor gene and its loss is associated with several cancer types, here we reported that MEG3 inhibition can be used for improving the efficiency of known chemotherapeutic drug sensitivity. We propose that the level of MEG3 should be evaluated in the treatment of different glioma subtypes that are resistant to effective drugs to increase the potential effective drug applications.     

Effect of Axial Ligand Length on Biological and Anticancer Properties of Axially Disubstituted Silicon Phthalocyanines

In this study, three new axially disubstituted silicon phthalocyanines ( SiPc1–3 ) and their quaternized phthalocyanine derivatives ( QSiPc1–3 ) were prepared and characterized. The biological properties (antioxidant, antimicrobial, antibiofilm, and microbial cell viability activities) of the water-soluble silicon phthalocyanines were examined, as well. A 1 % DMSO diluted with pure water was used as a solvent in biological activity studies. All the compounds exhibited high antioxidant activity. They displayed efficient antimicrobial and antimicrobial photodynamic therapeutic properties against various microorganisms, especially Gram (+) bacteria. Additionally, they demonstrated high antibiofilm activities against S. aureus and P. aeruginosa. In addition, 100 % bacterial reduction was obtained for all the studied phthalocyanines against E. coli viable cells. Besides, the DNA cleavage and binding features of compounds ( QSiPc1–3 ) were studied using pBR322 DNA and CT-DNA, respectively. Furthermore, the human topoisomerase I enzyme inhibition activities of compounds QSiPc1 – 3 were studied. Anticancer properties of the water-soluble compounds were investigated using cell proliferation MTT assay. They exhibited anticarcinogenic activity against the human colon cancer cell line (DLD-1). Compounds QSiPc1 and QSiPc3 displayed a high anticarcinogenic effect on the DLD-1 cell line. The obtained results indicated that all the studied compounds may be effective biological agents and anticancer drugs after further investigations.     

Metagenomics analysis of the fecal microbiota in Ring-necked pheasants (Phasianus colchicus) and Green pheasants (Phasianus versicolor) using next generation sequencing

Pheasant reintroduction and conservation efforts have been in place in Pakistan since the 1980 s, yet there is still a scarcity of data on pheasant microbiome and zoonosis. Instead of growing vast numbers of bacteria in the laboratory, to investigate the fecal microbiome, pheasants (green and ring neck pheasant) were analyzed using 16S rRNA metagenomics and using IonS5TMXL sequencing from two flocks more than 10 birds. Operational taxonomic unit (OTU) cluster analysis and phylogenetic tree analysis was performed using Mothur software against the SSUrRNA database of SILVA and the MUSCLE (Version 3.8.31) software. Results of the analysis showed that firmicutes were the most abundant phylum among the top ten phyla, in both pheasant species, followed by other phyla such as actinobacteria and proteobacteria in ring necked pheasant and bacteroidetes in green necked pheasant. Bacillus was the most relatively abundant genus in both pheasants followed by Oceanobacillus and Teribacillus for ring necked pheasant and Lactobacillus for green necked pheasant. Because of their well-known beneficial characteristics, these genus warrants special attention. Bird droppings comprise germs from the urinary system, gut, and reproductive sites, making it difficult to research each anatomical site at the same time. We conclude that metagenomic analysis and classification provides baseline information of the pheasant fecal microbiome that plays a role in disease and health.     

A novel homozygous 10 nucleotide deletion in BBS10 causes Bardet–Biedl syndrome in a Pakistani family

Bardet–Biedl Syndrome is a multisystem autosomal recessive disorder characterized by central obesity, polydactyly, hypogonadism, learning difficulties, rod-cone dystrophy and renal dysplasia. Bardet–Biedl Syndrome has a prevalence rate ranging from 1 in 100,000 to 1 in 160,000 births although there are communities where Bardet–Biedl Syndrome is found at a higher frequency due to consanguinity. We report here a Pakistani consanguineous family with two affected sons with typical clinical features of Bardet–Biedl Syndrome, in addition to abnormal liver functioning and bilateral basal ganglia calcification, the latter feature being typical of Fahr's disease. Homozygous regions obtained from SNP array depicted three known genes BBS10, BBS14 and BBS2. Bidirectional sequencing of all coding exons by traditional sequencing of all these three genes showed a homozygous deletion of 10 nucleotides (c.1958_1967del), in BBS10 in both affected brothers. The segregation analysis revealed that the parents, paternal grandfather, maternal grandmother and an unaffected sister were heterozygous for the deletion. Such a large deletion in BBS10 has not been reported previously in any population and is likely to be contributing to the phenotype of Bardet–Biedl Syndrome in this family.     

Quest for Novel Preventive and Therapeutic Options Against Multidrug-Resistant Pseudomonas aeruginosa

International Journal of Peptide Research and Therapeutics - Pseudomonas aeruginosa (P. aeruginosa) is a critical healthcare challenge due to its ability to cause persistent infections and the...     

Assessment of risk management and control measures against coronavirus disease

This article presents the COVID-19 situation and control measures taken by the Government of Pakistan. Two waves of pandemic are faced globally and similar in the study area. We have investigated the risk management decision in two phases. Primarily, strict lockdown was observed from March 2020 to July 2020 and smart lockdown was enforced from August 2020 to December 2020. It has been studied that during strict lockdown, COVID cases reduced gradually but reopening of institutes and smart lockdown strategy resulted gradual increase in confirmed cases and death rates. During first wave of COVID-19 in Pakistan, a total confirmed number of patients of COVID-19 were 263,496 till 18th of July 2020 with total deaths of 5,568 people and 204,276 recoveries, while total number of COVID-19 patients reached 555,511 till 9th of February 2021 with total deaths of 12,026 people. Province of Sindh was affected badly with total number of 251,434 COVID-19 cases followed by Punjab Province with total number of 161,347 COVID-19 till 9th of February 2020.     

Population genetic structure of turbot (Scophthalmus maximus L., 1758) in the Black Sea

Turbot, Scophthalmus maximus, is a commercially important demersal flatfish species distributed throughout the Black Sea. Several studies performed locally with a limited number of specimens using both mitochondrial DNA (mtDNA) and microsatellite markers evidenced notable genetic variation among populations. However, comprehensive population genetic studies are required to help management of the species in the Black Sea. In the present study eight microsatellite loci were used to resolve the population structure of 414 turbot samples collected from 12 sites across the Black Sea. Moreover, two mtDNA genes, COI and Cyt-b, were used for taxonomic identification. Microsatellite markers of Smax-04 and B12-I GT14 were excluded from analysis due to scoring issues. Data analysis was performed with the remaining six loci. Loci were highly polymorphic (average of 17.8 alleles per locus), indicating high genetic variability. Locus 3/20CA17, with high null allele frequency (>30%), significantly deviated from HW equilibrium. Pairwise comparison of the F_ST index showed significant differences between most of the surveyed sampling sites (P < 0.01). Cluster analysis evidenced the presence of three genetic groups among sampling sites. Significant genetic differentiation between Northern (Sea of Azov and Crimea) and Southern (Turkish Black Sea Coast) Black Sea sampling sites were detected. The Mantel test supported an isolation by distance model of population structure. These findings are vital for long-term sustainable management of the species and development of conservation programs. Moreover, generated mtDNA sequences would be useful for the establishment of a database for S. maximus.     

Biocontrol of wilt disease complex of pea using Pseudomonas fluorescens and Rhizobium sp.

Biocontrol of wilt disease complex of pea caused by the root-knot nematode Meloidogyne incognita and Fusarium oxysporum f. sp. pisi was studied on pea (Pisum sativum L.) using plant growth-promoting rhizobacterium Pseudomonas fluorescens and root nodule bacterium Rhizobium sp. Inoculation of M. incognita and F.oxysporum alone caused significant reductions in plant growth over un-inoculated control. Reduction in plant growth caused by M. incognita was statistically equal to that caused by F. oxysporum. Inoculation of M. incognita plus F. oxysporum together caused a greater reduction in plant growth than the sum of damage caused by these pathogens singly. Inoculation of P. fluorescens and Rhizobium sp. individually or both together increased plant growth in pathogen inoculated and un-inoculated plants. Inoculation of P. fluorescens to pathogen-inoculated plants caused a greater increase in plant growth than caused by Rhizobium sp. Application of Rhizobium plus P. fluorescens caused a greater increase in plant growth than caused by each of them singly. Inoculation of P.fluorescens caused higher reduction in galling and nematode multiplication than caused by Rhizobium sp. Use of Rhizobium plus P. fluorescens caused higher reduction in galling and nematode multiplication than their individual inoculation. Plants inoculated with both pathogens plus Rhizobium showed less nodulation than plants inoculated with single pathogen plus Rhizobium. Inoculation of Rhizobium plus P. fluorescens resulted in higher root-nodulation than inoculated only with Rhizobium. Wilting indices were 4 and 5, respectively, when plants were inoculated with F. oxysporum and F. oxysporum plus M. incognita. Wilting indices were reduced maximum to 1 and 2, respectively, when plants inoculated with F.oxysporum and plants with both pathogens were treated with P. fluorescens plus Rhizobium.