High morbidity and mortality in children with untreated congenital deficiency of leptin or its receptor.

The long-term clinical outcomes of severe obesity due to leptin signaling deficiency are unknown. We carry out a retrospective cross-sectional investigation of a large cohort of children with leptin (LEP), LEP receptor (LEPR), or melanocortin 4 receptor (MC4R) deficiency (n = 145) to evaluate the progression of the disease. The affected individuals undergo physical, clinical, and metabolic evaluations. We report a very high mortality in children with LEP (26%) or LEPR deficiency (9%), mainly due to severe pulmonary and gastrointestinal infections. In addition, 40% of surviving children with LEP or LEPR deficiency experience life-threatening episodes of lung or gastrointestinal infections. Although precision drugs are currently available for LEP and LEPR deficiencies, as yet, they are not accessible in Pakistan. An appreciation of the severe impact of LEP or LEPR deficiency on morbidity and early mortality, educational attainment, and the attendant stigmatization should spur efforts to deliver the available life-saving drugs to these children as a matter of urgency.

Genome mining of Pseudomonas spp. hints towards the production of under-pitched secondary metabolites.

The recent advances in omics and computational analysis have enabled the capacity to identify the exclusive strain-specific metabolites and novel biosynthetic gene clusters. This study analyzed eight strains of P. aurantiaca including GS1, GS3, GS4, GS6, GS7, FS2, ARS38, PBSt2, one strain of P. chlororaphis RP4, one strain of P. aeruginosa (At1RP4), and one strain of P. fluorescens (RS1) for the production of rhamnolipids, quorum-sensing signals, and osmolytes. Seven rhamnolipid derivatives were variably detected in fluorescent pseudomonads. These rhamnolipids included Rha-C10-C8, Rha-Rha-C10-C10, Rha-C10-C12db, Rha-C10-C10, Rha-Rha-C10-C12, Rha-C10-C12, and Rha-Rha-C10-C12db. Pseudomonas spp. also showed the variable production of osmoprotectants including N-acetyl glutaminyl glutamine amide (NAGGN), betaine, ectoine, and trehalose. Betaine and ectoine were produced by all pseudomonads, however, NAGGN and trehalose were observed by five and three strains, respectively. Four strains including P. chlororaphis (RP4), P. aeruginosa (At1RP4), P. fluorescens (RS1), and P. aurantiaca (PBSt2) were exposed to 1- 4% NaCl concentrations and evaluated for the changes in phenazine production profile which were negligible. AntiSMASH 5.0 platform showed 50 biosynthetic gene clusters in PB-St2, of which 23 (45%) were classified as putative gene clusters with ClusterFinder algorithm, five (10%) were classified as non-ribosomal peptides synthetases (NRPS), five (10%) as saccharides, and four (8%) were classified as putative fatty acids. The genomic attributes and comprehensive insights into the metabolomic profile of these Pseudomonas spp. strains showcase their phytostimulatory, phyto-protective, and osmoprotective effects of diverse crops grown in normal and saline soils. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03607-x.

Peripheral mRNA Expression and Prognostic Significance of Emotional Stress Biomarkers in Metastatic Breast Cancer Patients.

Emotional stress is believed to be associated with increased tumor progression. Stress-induced epigenetic modifications can contribute to the severity of disease and poor prognosis in cancer patients. The current study aimed to investigate the expression profiles along with the prognostic significance of psychological stress-related genes in metastatic breast cancer patients, to rationalize the molecular link between emotional stress and cancer progression. We profiled the expression of selected stress-associated genes (5-HTT, NR3C1, OXTR, and FKBP5) in breast cancer including the stress evaluation of all participants using the Questionnaire on Distress in Cancer Patients-short form (QSC-R10). A survival database, the Kaplan-Meier Plotter, was used to explore the prognostic significance of these genes in breast cancer. Our results showed relatively low expressions of 5-HTT (p = 0.02) and OXTR (p = 0.0387) in metastatic breast cancer patients as compared to the non-metastatic group of patients. The expression of NR3C1 was low in tumor grade III as compared to grade II (p = 0.04). Additionally, the expression of NR3C1 was significantly higher in patients with positive estrogen receptor status. However, no significant difference was found regarding FKBP5 expression in breast cancer. The results suggest a potential implication of these genes in breast cancer pathology and prognosis.

Profilin 3 genetic architecture in glioma formalin fixed paraffin embedded (FFPE) archive.

Pfn3 is an intron-less gene, encoding actin binding protein that affects structure of cytoskeleton. Although, Pfn3 is mentioned in Allen Brain Atlas and in adult and prenatal Human Brain Tissue Gene Expression Profiles dataset, however, no report on brain and/or brain tumor associated Pfn3 nucleotide sequences are available in the databases. Moreover, pfn3 and pfn4 are always considered as testicular specific genes. The current study explored transcriptional expression profile and genetic architecture of pfn3 in a cohort of fifty formalin fixed paraffin embedded (FFPE) human glioma archive tissues. Results of designed study highlighted the significant dysregulated transcriptional pattern of pfn3. Molecular similarity index indicated 97% in nucleotide and 93% homology in protein sequences (with clear differences in nine amino acid residues). Thus, molecular variations in the pfn3 may be corelated with the malignancy of brain tumors, as previously, pfn1 and pfn2 were reported as tumor suppressor genes in other types of cancer.