Target Therapy in Neuroblastoma

Neuroblastoma is an embryonal malignancy that originates in the sympathetic nervous system. It is the most common solid tumor in infants and the most frequent extracranial solid tumor in children. Neuroblastoma accounts for 10% of childhood malignancies with 75% occurring in children <4 years. Stage, age, clinical and tumor genomic features are the principal criteria for determining treatment policy. Treatment modalities traditionally employed in the management of neuroblastoma are surgery, chemotherapy, and radiotherapy. Intensive multimodal treatment in patients with neuroblastoma has resulted in improved survival rates. However, there is a considerable percentage of patients with refractory and relapsed disease. Targeted therapy for neuroblastoma involves treatment aimed at molecular targets that have a unique expression in this childhood cancer. A large number of molecular targets have been identified for the treatment of high-risk and relapsed neuroblastoma. Treatment in this way aims at providing a more selective way to treat the disease and decreasing toxicities associated with the conventional treatment regimen

The role of B-cells in immunity against adult Strongyloides venezuelensis

BACKGROUND: Strongyloides venezuelensis has been used as a tool and model for strongyloidiasis research. Elimination of S. venezuelensis adult worms from mice has been particularly associated with proliferation and activation of intestinal mast cells and eosinophils. To date, the role of B-cells in the protective mechanism against adult Strongyloides infection in experimental animals has not been reported in the literature. Therefore, the present study was carried to investigate the role of B-lymphocytes in immunity against adult S. venezuelensis infection using mice with a targeted deletion of the JH locus. METHODS: JHD knockout mice with its wild-type Balb/c mice were infected by intra-duodenal implantation of adult S. venezuelensis. Fecal egg count, intestinal worm recovery, mucosal mast cells and eosinophils were counted. RESULTS: At day 11 post infection, parasites in wild-type mice stopped egg laying, while in JHD knockout mice parasites continued to excrete eggs until the end of the observation period, day 107. The higher number of parasite eggs expelled in the feces of JHD knockout infected mice was a consequence of higher worm burdens, which established in the small intestine of these animals. On the other hand worm fecundity was comparable in both groups of mice. Both B-cell-deficient mice and wild-type mice, showed an influx of mucosal mast cells and eosinophils. The absolute numbers in JHD knockout mice were lower than those seen in wild-type mice at day 11, but not to a level of significance. JHD knockout mice could not recover from infection despite the recruitment of both types of cells. CONCLUSION: Our findings highlight a role of B cells in mucosal immunity against invasion of adult S. venezuelensis and in its expulsion. Therefore, we conclude that B-cells together with mucosal mast cells and eosinophils, contribute to immunity against adult S. venezuelensis by mechanism(s) to be investigated

Comparative Genetic Diversity Assessment and Marker–Trait Association Using Two DNA Marker Systems in Rice (<i>Oryza sativa</i> L.)

In this paper, the genetic diversities of 12 rice genotypes (Oryza sativa L.), representing Indica, Japonica, and Indica–Japonica varieties, were assessed using twelve ISSR and five SSR markers. In addition, the rice genotypes were evaluated for 11 agro-morphological traits in a two-year trial. Association mapping was performed to detect any association between the DNA markers and the agro-morphological traits. An association analysis was conducted considering the relative kinship among the genotypes and accounting for the population structure using the unified mixed-model approach to avoid possible false-positive associations. Seventy-three alleles were collectively produced by ISSRs and SSRs, with an average of 6.3 and 2.8 alleles per locus, respectively. Both marker systems were informative, and the average polymorphism information content (PIC) was 0.222 and 0.352 for ISSRs and SSRs, respectively. The average expected heterozygosity (Hexp) was 0.264 for ISSRs compared to 0.457 for SSRs. After using the false discovery rate (FDR) method, the association analysis revealed a total of 12 significant marker–trait associations with six agro-morphological traits, including the no. of unfiled grains panicle−1, panicle length, panicle weight, the no. of panicles plant−1, the no. of tillers plant−1, and 1000-grain weight. ISSRs showed seven significant associations with five markers, while SSRs showed three significant associations with three markers. The phenotypic variance (R2) explained by each marker ranged between 29.2% for the ISSR marker HB11 (associated with 1000-grain weight) and 49.3% for the ISSR marker HB8 (associated with the no. of tillers plant−1). The identified marker–trait associations reported herein may improve the expected gain of future molecular-based rice-breeding programs, particularly those designed for improving grain-related or harvest-related traits

Comparative Genetic Diversity Assessment and Marker&ndash;Trait Association Using Two DNA Marker Systems in Rice (Oryza sativa L.)

In this paper, the genetic diversities of 12 rice genotypes (Oryza sativa L.), representing Indica, Japonica, and Indica&ndash;Japonica varieties, were assessed using twelve ISSR and five SSR markers. In addition, the rice genotypes were evaluated for 11 agro-morphological traits in a two-year trial. Association mapping was performed to detect any association between the DNA markers and the agro-morphological traits. An association analysis was conducted considering the relative kinship among the genotypes and accounting for the population structure using the unified mixed-model approach to avoid possible false-positive associations. Seventy-three alleles were collectively produced by ISSRs and SSRs, with an average of 6.3 and 2.8 alleles per locus, respectively. Both marker systems were informative, and the average polymorphism information content (PIC) was 0.222 and 0.352 for ISSRs and SSRs, respectively. The average expected heterozygosity (Hexp) was 0.264 for ISSRs compared to 0.457 for SSRs. After using the false discovery rate (FDR) method, the association analysis revealed a total of 12 significant marker&ndash;trait associations with six agro-morphological traits, including the no. of unfiled grains panicle&minus;1, panicle length, panicle weight, the no. of panicles plant&minus;1, the no. of tillers plant&minus;1, and 1000-grain weight. ISSRs showed seven significant associations with five markers, while SSRs showed three significant associations with three markers. The phenotypic variance (R2) explained by each marker ranged between 29.2% for the ISSR marker HB11 (associated with 1000-grain weight) and 49.3% for the ISSR marker HB8 (associated with the no. of tillers plant&minus;1). The identified marker&ndash;trait associations reported herein may improve the expected gain of future molecular-based rice-breeding programs, particularly those designed for improving grain-related or harvest-related traits

Rare Acetogenins with Anti-Inflammatory Effect from the Red Alga <i>Laurencia obtusa</i>

Three new rare C12 acetogenins (enyne derivatives 1&#8315;3) were isolated from the organic extract obtained from the red alga Laurencia obtusa, collected from the Red Sea. The chemical structures of the isolated compounds were established by spectroscopical data analyses. Potent anti-inflammatory effect of the isolated metabolites was evidenced by inhibition of the release of inflammatory mediators (e.g., TNF-&#945;, IL-1&#946; and IL-6) by employing Human Peripheral Blood Mononuclear Cells (PBMC)

Subtyping of Blastocystis sp. isolated from symptomatic and asymptomatic individuals in Makkah, Saudi Arabia

Abstract Background Blastocystis is a group of cosmopolitan gastrointestinal parasite of humans and a wide variety of animals. These anaerobic protozoans include more than 17 specific small-subunit ribosomal RNA subtypes, of which nine are found in humans with a variable geographical distribution. Until now, no study has described the Blastocystis subtypes present in Saudi Arabia. Methods In total, 1,262 faecal samples were collected from patients with gastrointestinal complaints and asymptomatic individuals visiting two major hospitals. All samples were analysed by F1/R1 diagnostic PCR, microscopy and culture methods. The subtypes of Blastocystis sp. isolates were determined by the sequenced-tagged site (STS)-based method. Results One-hundred-thirty-three positive cases were detected by F1/R1 diagnostic PCR, of which 122 were also positive by the culture method and 83 by direct microscopy. The sensitivities of direct microscopy and the culture method were 62% and 92%, respectively. Subtype (ST3) was the most prevalent (80.5%), followed by ST1 (14.5%) and ST2 (5%). ST4, ST5, ST6 and ST7 were not detected in this study. ST3 infections were significantly predominant (P < 0.05) among symptomatic patients. Conclusions To our knowledge, this study provides the first run-through information on Blastocystis sp. epidemiology in Makkah city, revealing a rather moderate prevalence of 10.5% and the presence of three subtypes, ST1, ST2, and ST3. ST3 was the most predominant, particularly among symptomatic patients

MXene (Ti₃C₂T_x)-Embedded Nanocomposite Hydrogels for Biomedical Applications: A Review

Polymeric nanocomposites have been outstanding functional materials and have garnered immense attention as sustainable materials to address multi-disciplinary problems. MXenes have emerged as a newer class of 2D materials that produce metallic conductivity upon interaction with hydrophilic species, and their delamination affords monolayer nanoplatelets of a thickness of about one nm and a side size in the micrometer range. Delaminated MXene has a high aspect ratio, making it an alluring nanofiller for multifunctional polymer nanocomposites. Herein, we have classified and discussed the structure, properties and application of major polysaccharide-based electroactive hydrogels (hyaluronic acid (HA), alginate sodium (SA), chitosan (CS) and cellulose) in biomedical applications, starting with the brief historical account of MXene’s development followed by successive discussions on the synthesis methods, structures and properties of nanocomposites encompassing polysaccharides and MXenes, including their biomedical applications, cytotoxicity and biocompatibility aspects. Finally, the MXenes and their utility in the biomedical arena is deliberated with an eye on potential opportunities and challenges anticipated for them in the future, thus promoting their multifaceted applications

Microneedle-Based Natural Polysaccharide for Drug Delivery Systems (DDS): Progress and Challenges

In this focused progress review, the most widely accepted methods of transdermal drug delivery are hypodermic needles, transdermal patches and topical creams. However, microneedles (MNs) (or microneedle arrays) are low-invasive 3D biomedical constructs that bypass the skin barrier and produce systemic and localized pharmacological effects. In the past, biomaterials such as carbohydrates, due to their physicochemical properties, have been extensively used to manufacture microneedles (MNs). Due to their wide range of functional groups, carbohydrates enable the design and development of tunable properties and functionalities. In recent years, numerous microneedle products have emerged on the market, although much research needs to be undertaken to overcome the various challenges before the successful introduction of microneedles into the market. As a result, carbohydrate-based microarrays have a high potential to achieve a future step in sensing, drug delivery, and biologics restitution. In this review, a comprehensive overview of carbohydrates such as hyaluronic acid, chitin, chitosan, chondroitin sulfate, cellulose and starch is discussed systematically. It also discusses the various drug delivery strategies and mechanical properties of biomaterial-based MNs, the progress made so far in the clinical translation of carbohydrate-based MNs, and the promotional opportunities for their commercialization. In conclusion, the article summarizes the future perspectives of carbohydrate-based MNs, which are considered as the new class of topical drug delivery systems