We investigated possible anti-diabetic effect of ferrocene-based acyl ureas: 4-ferrocenyl aniline (PFA), 1-(4-chlorobenzoyl)-3-(4-ferrocenylphenyl) urea (DPC1), 1-(3-chlorobenzoyl)-3-(4-ferrocenylphenyl) urea (DMC1), 1-(2-chlorobenzoyl)-3-(4-ferrocenylphenyl) urea (DOC1) and homoleptic cadmium carboxylates: bis (diphenylacetato) cadmium (II) (DPAA), bis (4-chlorophenylacetato) cadmium (II) (CPAA), using in silico and in vivo techniques. PFA, DPC1, DMC1, DOC1, DPAA and CPAA exhibited high binding affinities (ACE ≥ −350 Kcal/mol) against targets: aldose reductase, peroxisome proliferator-activated receptor γ, 11β-hydroxysteroid dehydrogenase-1, C-alpha glucosidase and glucokinase, while showed moderate affinities (ACE ≥ −250 Kcal/mol) against N-alpha glucosidase, dipeptidyl peptidase-IV, phosphorylated-Akt, glycogen synthase kinase-3β, fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase, whereas revealed lower affinities (ACE < −250 Kcal/mol) vs. alpha amylase, protein tyrosine phosphatases 1B, glycogen phosphorylase and phosphatidylinositol 3 kinase. In alloxan (300 mg/Kg)-induced diabetic mice, DPAA and DPC1 (1–10 mg/Kg) at day 1, 5, 10, 15, and 20th decreased blood glucose levels, compared to diabetic control group and improved the treated animals body weight. DPAA (10 mg/Kg) and DPC1 (5 mg/Kg) in time-dependent manner (30–120 min.) enhanced tolerance of oral glucose overload in mice. DPAA and DPCI dose-dependently at 1, 5, and 10 mg/Kg decreased glycosylated hemoglobin levels in diabetic animals, as caused by metformin. These results indicate that aforementioned derivatives of ferrocene and cadmium possess anti-diabetic potential.
Osteopetrosis is a genetically heterogenous, fatal bone disorder characterized by increased bone density. Globally, various genetic causes are reported for osteopetrosis with all forms of inheritance patterns. A precise molecular diagnosis is necessary for prognosis and for prescribing treatment paradigms in osteopetrosis. Here we report on thirteen individuals diagnosed with infantile malignant osteopetrosis coming from ten unrelated Pakistani families; nine of whom are consanguineous. We performed whole exome sequencing and Sanger sequencing in all families and identified homozygous variants in genes previously reported for autosomal recessive inheritance of osteopetrosis. All the identified variants are expected to affect the stability or length of gene products except one nonsynonymous missense variant. TCIRG1 was found as a candidate causal gene in majority of the families. We report six novel variants; four in TCIRG1 and one each in CLCN7 and OSTM1. Our combined findings will be helpful in molecular diagnosis and genetic counselling of patients with osteopetrosis particularly in populations with high consanguinity.
Astrocytes are the most abundant cells of the central nervous system. These cells are of diverse types based on their function and structure. Astrocyte activation is linked mainly with microbial infections, but long-term activation can lead to neurological impairment. Astrocytes play a significant role in neuro-inflammation by activating pro-inflammatory pathways. Activation of interleukins and cytokines causes neuroinflammation resulting in many neurodegenerative disorders such as stroke, growth of tumours, and Alzheimer’s. Inflammation of the brain hinders neural circulation and compromises blood flow by affecting the blood–brain barrier. So the oxygen concentration is lowered, causing brain hypoxia. Hypoxia leads to the activation of nuclear factor kappa B (NFkB) and hypoxia-inducible factors (HIF), which aggravates the inflammatory state of the brain. Hypoxia evoked changes in the blood–brain barrier, further complicating astrocyte-induced pathogenesis.
The focus of this study is to get an in-depth understanding of the importance and need for Career Counseling at the Grade 12 level because career counseling at this level helps students in selecting the appropriate study program in line with their future career choice. The study was guided by 5 research questions including; what are the perspectives of grade 12 students about career counseling? To what extent career counseling is provided to grade 12 students at school? What are the benefits of career counseling for grade 12 students? What are the issues related to career counseling for grade 12 students? And how do the issues related to career counseling for grade 12 students be resolved? Purposefully selected research participants of this study were 6 students who were studying at grade 12 level at a semi-public sector school of Sukkur city. A qualitative case study approach has been used, with a semi-structured interview guide for collecting data. Data were analyzed by an open coding strategy and is reported thematically. It is anticipated that this study will help students, teachers, parents, educational institutes, and policymakers to a greater extent. Career counseling is becoming people-oriented and so with the findings of this study, policymakers can make new policies and implement them in the system. Future research can be conducted in different public and private sector schools of Sindh. Research participants from different education systems will provide a deeper analysis of different views and perspectives of students in different settings.
Background: Osteopoikilosis is a benign, uncommon disorder that is inherited by the autosomal dominant gene. Multiple benign enostoses are present in this specific kind of sclerosing skeletal dysplasia, which can be mistaken for osteoblastic skeletal metastases. Case Presentation: We present here a case of 50-year-old male patient with pain in lower back for 3 months. His pelvic X-ray showed few sclerotic rounded lesions in ilium, acetabulum and proximal femur. His MRI pelvis showed T1WI and T2WI hypo intense focal lesions in ilium and acetabulum. His 99mTc MDP bone scan was done showing no focal abnormal uptake in lesion reported on pelvic X-ray and MRI. These features are suggestive of Osteopoikilosis, ruling out osteoblastic skeletal metastasis. Conclusion: Osteopoikilosis is usually an incidental finding on radiograph. Both x-ray and MRI findings can mimic skeletal metastasis, but a normal bone scan can rule out metastasis and is useful if metastatic disease is thought to be a possibility.
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