Immune checkpoint inhibitors in the treatment of hepatocellular carcinoma.

Despite advances in cancer treatment, hepatocellular carcinoma (HCC), the most common form of liver cancer, remains a major public health problem worldwide. The immune microenvironment plays a critical role in regulating tumor progression and resistance to therapy, and in HCC, the tumor microenvironment (TME) is characterized by an abundance of immunosuppressive cells and signals that facilitate immune evasion and metastasis. Recently, anti-cancer immunotherapies, therapeutic interventions designed to modulate the immune system to recognize and eliminate cancer, have become an important cornerstone of cancer therapy. Immunotherapy has demonstrated the ability to improve survival and provide durable cancer control in certain groups of HCC patients, while reducing adverse side effects. These findings represent a significant step toward improving cancer treatment outcomes. As demonstrated in clinical trials, the administration of immune checkpoint inhibitors (ICIs), particularly in combination with anti-angiogenic agents and tyrosine kinase inhibitors, has prolonged survival in a subset of patients with HCC, providing an alternative for patients who progress on first-line therapy. In this review, we aimed to provide an overview of HCC and the role of the immune system in its development, and to summarize the findings of clinical trials involving ICIs, either as monotherapies or in combination with other agents in the treatment of the disease. Challenges and considerations regarding the administration of ICIs in the treatment of HCC are also outlined.

Surface defects due to bacterial residue on shrimp shell.

The changes in the surface chemistry and morphological structure of chitin forms obtained from shrimp shells (ShpS) with and without microorganisms were evaluated. Total mesophilic aerobic bacteria (TMAB), estimated Pseudomonas spp. and Enterococcus spp. were counted in Shp-S by classical cultural counting on agar medium, where the counts were 6.56 ± 0.09, 6.30 ± 0.12, and 3.15 ± 0.03 CFU/g, respectively. Fourier Transform Infrared (FTIR) Spectroscopy and Scanning Electron Microscopy (SEM)/Energy dispersed X-ray (EDX) were used to assess the surface chemistry/functional groups and morphological structure for ChTfree (non-microorganism), and ChTmo (with microorganisms). ChTfree FTIR spectra presented a detailed chitin structure by OH, NH, and CO stretching vibrations, whereas specific peaks of chitin could not be detected in ChTmo. Major differences were also found in SEM analysis for ChTfree and ChTmo. ChTfree had a flat, prominent micropore, partially homogeneous structure, while ChTmo had a layered, heterogeneous, complex dense fibrous, and lost pores form. The degree of deacetylation was calculated for ChTfree and ChTmo according to FTIR and EDX data. The results suggest that the degree of deacetylation decreases in the presence of microorganisms, affecting the production of beneficial components negatively. The findings were also supported by the molecular docking model.

Genetic diversity and population structure of Saccharomyces cerevisiae isolated from Turkish sourdough by iPBS-retrotransposons markers.

Molecular DNA markers are valuable tools for analyzing genetic variation among yeast from different populations to reveal the genetically different autochthonous strains. In this study, we employed inter-primer binding site (iPBS) retrotransposon polymorphism to assess the genetic variation and population structure of 96 Saccharomyces cerevisiae isolates from four different regions in Turkey. The nine selected iPBS primers amplified 102 reproducible and scorable bands, of which 95.10% were polymorphic with an average of 10.78 polymorphic fragments per primer. The average polymorphism information content and the resolving power were 0.26-3.58, respectively. Analysis of molecular variance (AMOVA) revealed significant (P < 0.001) genetic differences within populations (88%) and between populations (12%). The unweighted pair group mean with arithmetic (UPGMA) dendrogram grouped 96 S. cerevisiae strains into two main clusters, where the highest probability of the data elucidating the population structure was obtained at ΔK = 2. There was not an obvious genetic discrimination of the populations according to geographical regions on UPGMA, supported by principal coordinate analysis. However, the individuals of the closer provinces in each population were more likely to group together or closely. The results indicate that iPBS polymorphism is a useful tool to reveal the genetically diverse autochthonous S. cerevisiae strains that may be important for the production of sourdough or baked goods.

Start Codon Targeted (SCoT) markers for the assessment of genetic diversity in yeast isolated from Turkish sourdough.

Molecular markers are valuable tools for assessing the genetic variation in yeast. Here, we investigated the utility of SCoT markers for the genetic characterization of yeast strains at inter and intraspecies levels. A total of 345 endogenous yeast strains were isolated from 65 Type I sourdough samples collected from six different regions of Turkey. The seven SCoT primers produced 221 bands, of which 95.47% were polymorphic. Each primer could successfully differentiate species, supported by PIC and RP values. The ITS sequencing of isolates selected from the UPGMA dendrogram revealed that Saccharomyces cerevisiae predominated the microflora, followed by Kazachstania servazzii, K. humilis, Wickerhamomyces anomalus, Torulaspora delbrueckii, and Pichia kudriavzevii, respectively. The AMOVA revealed a high genetic variation between (49%) and within populations (51%) for S. cerevisiae. The high gene flow observed among S. cerevisiae populations suggests that it may have contributed to the geographical evolution of S. cerevisiae via the transportation of the sourdough samples. The different geographical origins were most likely to group separately on the UPGMA and PCoA. Saccharomyces cerevisiae strains from more distant populations generally displayed more significant genetic variation. SCoT markers can successfully be used alone or with the other existing DNA markers for DNA fingerprinting and analyzing the genetic variation between and within species.

The utility of iPBS retrotransposons markers to analyze genetic variation in yeast.

Yeasts are one of the main organisms in the food industry and effective components of many ecosystems. The method for identifying and detecting certain yeast species or strains is a crucial step for the food industry and should be simple, reliable, fast, and inexpensive. In our study, inter-priming binding sites (iPBS) retrotransposon marker system was employed to elucidate the genetic variability at intraspecies and interspecies levels among 112 yeast strains belonging to eight species previously obtained from fermented foods. The molecular identification of yeast strains was firstly confirmed by sequencing the D1/D2 domain of the 26S rRNA. The eight selected retrotransposon-based primers produced 278 bands, all of which were polymorphic with an average of 34.75 polymorphic fragments per primer. The averages of polymorphism information contents and the resolving power values for the iPBS marker system were 0.23 and 10.11, respectively. The genetic parameters within each yeast species obtained from iPBS markers were observed as; the percentage of polymorphic loci for each species ranging from 19.23% to 71.21%, Nei's gene diversity from 0.085 to 0.228, while Shannon's information index values ranging from 0.125 to 0.349. The value of gene flow (0.09) and genetic variation among the populations (0.85) showed higher genetic variation among the species. UPGMA analyses demonstrated considerable genetic variability in the yeast strains, clustered them according to their species, and revealed the intraspecific variation. Each of the selected iPBS primer provided enough species-discrimination. Present evaluations suggest the utility of iPBS marker system to estimate the genetic variation of yeast strains. This study is a preliminary point for further studies on the identification methodology, and population genetics of yeast species having importance in the food industry with iPBS markers.