Does presence of complex translocations involving BCR::ABL1 in chronic myeloid leukemia affect the response rate to tyrosine kinase inhibitors? A systematic review of the literature.

Philadelphia (Ph) chromosome (9;22)(q34;q11) comprises 90-95 % of chronic myeloid leukemia (CML), while 5-10 % of CML have translocations involving three or more chromosomes. The outcome of treating patients harbouring complex Ph-positive cytogenetics with tyrosine kinase inhibitors (TKI) is unclear. In the present systematic review, we aim to summarise the response of patients with complex Ph-positive cytogenetics to treatment with TKI therapy. We collated all available literature from databases such as PubMed, Google Scholar, Web of Science database, Cochrane library, Scopus and Embase (up until January 31st, 2024), which describe cases of patients with CML, harbouring complex Ph-positive variations (three and four-way translocations), and summarised their response to TKI therapy. The studies were screened for the following criteria: documented TKI intervention and outcome (whether CR was achieved). Studies that did not report the same, were excluded. Additionally, we report a case from our center of a 55-year-old patient with CML, positive for the Ph-chromosome, harbouring a three-way translocation involving chromosome 15 i.e. 46XX, t(9;15;22) (q34;p11;q11). Identification of BCR::ABL and involvement of chromosome 15 was carried out using conventional cytogenetics, fluorescence in situ hybridization (FISH), and quantitative PCR (qPCR). Based on the inclusion criteria, a total of 15 studies were included from which a total of 87 cases were covered. Overall, we identified 38 unique complex three- and four-way translocations across 87 Ph-positive cases and found that 85 patients with complex Ph-positive cytogenetics achieved complete remission upon treatment and did not appear to have a lesser response to TKI therapy.

Exosomal long non-coding RNA MALAT1: a candidate of liquid biopsy in monitoring of Wilms' tumor.

PURPOSE: Wilms' tumor (WT) is a rare kidney cancer that primarily affects children. Exosomes are extracellular vesicles that cargo nucleic acids, proteins,etc. for cellular communication. Long non-coding RNAs (lncRNAs) have utility as biomarkers for cancer diagnosis, prognosis, and disease monitoring. We hypothesize that expression of lncRNA, metastasis-associated lung adenocarcinoma transcript-1(MALAT1), is dysregulated and possibly trafficked within exosomes to influence the tissue microenvironment for metastasis and recurrence of WT. METHODS: We investigated the expression of MALAT1 in thirty WT samples by qPCR. Exosomes were isolated using a precipitated and affinity-binding-based kit, and characterized using TEM, NTA, and DLS. RESULTS: Mean number of exosomes was 9.01×108/mL in primary culture, 1.64×108/mL in urine, and 4.65×108/plasma:400µl. Average yield of total RNA was 1.28µg (primary-culture supernatant:1ml), 1.47µg (Urine:1ml), 1.65µg (Plasma:400 µL). We quantified MALAT1 in exosomes derived from these sources in patients of WT. Expression of MALAT1 was significantly downregulated (p=0.008) in WT samples. CONCLUSION: This is the first study that demonstrated the presence of lncRNA MALAT1 in various invasive and non-invasive samples of patients with WT(primary tissue culture, urine, and plasma samples).

Expression of long non-coding RNA UCA1 and its clinical relevance in paediatric acute myeloid leukemia.

The underlying mechanisms and clinical significance of long non-coding RNA (lncRNA) urothelial cancer associated 1 (UCA1) is largely unknown in acute myeloid leukemia (AML). We aimed to study the expression of lncRNA UCA1, and its biological and clinical relevance in AML. Expression of lncRNA UCA1 was quantified in peripheral blood (PB) samples of children with de novo AML (n=69), post-induction, after achieving complete remission (CR) (n=8), and in patients who had relapsed (n=10). Additionally, two external cohorts were analysed i.e., TCGA-LAML dataset and Leukemia-MILE study. We also quantified expression in four different AML cell lines and analysed expression after cell differentiation. A consistent pattern of low UCA1 expression in AML was observed in our cohort of sixty-nine patients at baseline (P < 0.0001) and in the TCGA and Leukemia-MILE datasets. In patients who achieved remission, expression was comparable to healthy individuals, while relapsed patients interestingly had lower levels of UCA1 (P=0.0002). Furthermore, lncRNA UCA1 expression was significantly lower in AML cell lines (THP-1, P=0.0112; KG-1, P=0.0168; and HL-60, P=0.0112) and increased when THP-1 cells were differentiated (P=0.0001). In our AML patient cohort, lower expression was significantly associated with CR (P=0.043), however, the impact on survival (EFS and OS) was not significant. This is the first study wherein the lncRNA UCA1 expression was studied in various AML cell lines along with AML patients at baseline, remission and relapse. In conclusion, we found that UCA1 is significantly downregulated in AML compared to healthy individuals and mature differentiated cells.

Green Synthesis of Silver Nanoparticles from Camellia sinensis and Its Antimicrobial and Antibiofilm Effect against Clinical Isolates.

The green synthesis method of was used for the synthesis of silver nanoparticles using Camellia sinensis (green tea). The Camellia sinensis silver nanoparticles (CS-AgNPs) were characterized using different techniques, including UV-Vis (ultra violet-visible), SEM (scanning electron microscopy), TEM (transmission electron microscopy), and XRD (X-ray diffraction). The average size of the CS-AgNPs was 52 nm, according to TEM. The CS-AgNPs showed excellent antibacterial and antifungal activity. The MIC (minimum inhibitory concentration) against bacterial isolates varied from 31.25 to 62.5 µg/mL, whereas for fungal isolates, the MIC varied from 125 to 250 µg/mL. The presence of a zone in the well diffusion assay showed the antimicrobial nature of CS-AgNPs. Further, CLSM (confocal laser scanning microscopy) showed that CS-AgNPs possess antibiofilm activity. The interaction of CS-AgNPs with the Candidal cells was analyzed using TEM, and it was revealed that CS-AgNPs entered the cell and disrupted the cell machinery.

Biogas production and nutrients removal from slaughterhouse wastewater using integrated anaerobic and aerobic granular intermittent SBRs - Bioreactors stability and microbial dynamics.

Slaughterhouse wastewater (SWW) was effectively treated in sequential anaerobic and aerobic granular intermittent sequencing batch reactors (ASBR+ISBR) for 665 days at different HRTs (48 h, 32 h, 24 h, and 12 h). The ASBR was stable at each HRT but performed relatively well at 12 h (OLR - 7.8-9.8 kg COD/m3-d) in terms of pollutants removal and biogas production than previously conducted research. The average biogas production was about 17.3 L/day having 70-76 % of CH4 which could subsidize around 52 % of electricity demand while saving 103 US dollars/day if installed at full scale. In the case of post aerobic granular ISBR, carbon and nutrients removal (N&P) was achieved by enriching granules (1.7-2.2 mm) at low DO (0.5-0.8 mg/L) via the nitrite pathway. The ISBR was also well stable at 12 h HRT (average OLR of 2.1 kg COD/m3-d) and met the effluent discharge guidelines recommended by the Central Pollution Control Board of India. During steady-state conditions (12 h HRT), the average removal efficiencies for COD, TSS, O&G, TN, and PO4-P were 98.8 %, 96.4 %, 98.7 %, 93.4 %, and 86.6 % respectively from combined ASBR and ISBR. The microbial analysis confirmed Euryarchaeota, Proteobacteria, Firmicutes, Chloroflexi, Bacteroidetes, Planctomycetes, and Synergistetes as the dominant phyla in ASBR. Methanosaeta (21.56 %) and Methanosarcina (6.48 %) were the prevailing methanogens for CH4 production. The leading phyla observed in ISBR were Bacteroidetes, Proteobacteria, Firmicutes, Armatimonadetes, Verrucomicrobia, Chloroflexi, and Planctomycetes. Heterotrophic AOB (Thauera, Xanthomonadaceae, Pseudomonas, Sphingomonadaceae, and Rhodococcus) were mainly detected in the system for ammonia oxidation besides common autotrophic AOB. Similarly, a known PAO (Accumulibacter) was not identified but other PAO (Rhodocyclaceae, Dechloromonas, Pseudomonas, Flavobacteriaceae, and Sphingobacteriaceae) were prevalent inside aerobic granular ISBR that contributed to both carbon and nutrients removal. The results obtained would help implement the investigated reactor configurations at the pilot and full scale for SWW treatment.

Remote ischemic preconditioning-induced neuroprotection in cerebral ischemia-reperfusion injury: Preclinical evidence and mechanisms.

Remote ischemic preconditioning (RIPC) is an intrinsic protective phenomenon in which 3 to 4 interspersed cycles of non-fatal regional ischemia followed by reperfusion to the remote tissues protect the vital organs including brain, heart and kidney against sustained ischemia-reperfusion-induced injury. There is growing preclinical evidence supporting the usefulness of RIPC in eliciting neuroprotection against focal and global cerebral ischemia-reperfusion injury. Scientists have explored the involvement of HIF-1α, oxidative stress, apoptotic pathway, Lcn-2, platelets-derived microparticles, splenic response, adenosine A1 receptors, adenosine monophosphate activated protein kinase and neurogenic pathway in mediating RIPC-induced neuroprotection. The present review discusses the early and late phases of neuroprotection induced by RIPC against cerebral ischemic injury in animals along with the various possible mechanisms.

Effect of wheat bran and dried carrot pomace addition on quality characteristics of chicken sausage.

OBJECTIVE: Effect of addition of wheat bran (WB) and dried carrot pomace (DCP) on sensory, textural, colour, physico-chemical and nutritional characteristics of chicken sausage were evaluated. METHODS: WB and DCP were used as a source of dietary fibre at 3%, 6%, and 9% level individually. Different quality attributes of sausages were estimated. One product from each source with very good sensory acceptability was selected to analyze dietary fibre content and shelf life under refrigerated storage. RESULTS: Sensory acceptability of 3% fibre enriched sausage was comparable with control and a further increase in fibre level resulted in a decrease in sensory acceptability. Fibre enriched sausages were significantly harder and less cohesive than control sausage. Significant increase in gumminess and chewiness was observed at 6% level in WB treated sausages and 9% level in DCP treated sausages. Moisture content decreased significantly in all treated sausages, protein content decreased significantly in DCP-2 and DCP-3 sausages while fat content decreased in all WB and DCP-3 treated sausages in comparison to control. The fibre enriched sausage had significantly higher dietary fibre and lower cholesterol content. Cooking yield and emulsion stability increased in treated sausages and a significant difference was noticed at 6% level in both types of sausages. pH of WB treated sausages was significantly higher and DCP treated sausage significantly lower in comparison to control. CONCLUSION: The results of present study indicate that fibre enriched chicken sausage with moderate acceptability can be developed by incorporating WB and DCP each up to 9% level. Chicken sausage with very good acceptability, higher dietary fibre content and storability up to 15 days at refrigerated temperature can be developed by incorporating WB and DCP at 6% level each.