Unlocking Synergistic Potential: Agomelatine Enhances the Chemotherapeutic Effect of Paclitaxel in Breast Cancer Cell Through MT1 Melatonin Receptors and ER-alpha Axis

This study investigates the potential of agomelatine (AGO), a synthetic melatoninergic drug, in combination with paclitaxel (PTX) for the treatment of breast cancer. The effects of AGO, PTX and melatonin (MTN) on breast cancer cell viability were investigated, focusing on the role of MT1 receptors. Cell viability and gene expression were analyzed in MCF-7 and MDA-MB-231 breast cancer cell experiments. The results show that AGO has cytotoxic effects on breast cancer cells similar to MTN. Combining AGO and MTN with PTX showed synergistic effects in MCF-7 cells. The study also reveals differences in the molecular mechanisms of breast cancer between estrogen-positive MCF-7 cells and estrogen-negative MDA-MB-231 cells. Combination with AGO and PTX affects apoptosis-associated proteins in both cell types. The findings suggest that AGO, combined with PTX, may be a promising adjuvant therapy for breast cancer and highlight the importance of MTN receptors in its mechanism of action.     

31 cases with oculoauriculovertebral dysplasia (Goldenhar syndrome): clinical, neuroradiologic, audiologic and cytogenetic findings

Goldenhar syndrome (GS) or oculoauriculovertebral dysplasia (OAVD) is characterized by pre-auricular skin tags, microtia, facial asymmetry, ocular abnormalities and vertebral anomalies of different size and shape. The phenotypical findings of this syndrome are variable due to heterogenous aetiology. For that reason, the physician sometimes faces difficulty when making a definite diagnosis of OAVD. We reviewed the clinical and laboratory findings of 31 patients (15 boys and 16 girls) aged from 1 day to 16 years with the clinical diagnosis of GS. The characteristic features were pre-auricular skin tags (90%), microtia (52%), hemifacial microsomia (77%) and epibulbar dermoids (39%). Vertebral anomalies were noted in 70% of the patients. Cardiac malformations were found in 39% while a genitourinary anomaly was noted in 23% and various central nervous system malformations in 47%. There were 3 pregnancies following an intracytoplasmic sperm injection (ICSI) technique among the 31 patients. Two patients with GS came from the same family. Their relatives had hydrocephaly, myelomeningocele and neural tube defects. It is known that some chromosomal aberrations are seen in GS. We performed chromosome analysis of 29 patients. Among these cases, only one patient with severe mental and motor retardation had a 47,XX,+der(22)t(11,22)(q23; q11 karyotype due to a maternal balanced translocation t(11;22)(q23;q11). This translocation was demonstrated in her sister, brother and maternal uncle. Additionally CATCH 22 analysis in 13 cases with OAVD with a CATCH 22 phenotype revealed no deletion. OAVD patients present with different morphologic features and systemic manifestations. A multidisciplinary approach should be undertaken by departments such as pediatric cardiology, audiology, ophthalmology and plastic surgery when evaluating patients with OAVD. Chromosome analysis should be performed in every patient with Goldenhar syndrome.     

Oral self-nanoemulsifying formulation of GLP-1 agonist peptide exendin-4: development,characterization and permeability assesment on Caco-2 cell monolayer

Amino Acids - The objective of this study was to prepare a stable self-nanoemulsifying formulation of exendin-4, which is an antidiabetic peptide. As exendin-4 is commercially available only in...     

Reticulon-like REEP4 at the inner nuclear membrane promotes nuclear pore complex formation

Nuclear pore complexes (NPCs) are channels within the nuclear envelope that mediate nucleocytoplasmic transport. NPCs form within the closed nuclear envelope during interphase or assemble concomitantly with nuclear envelope reformation in late stages of mitosis. Both interphase and mitotic NPC biogenesis require coordination of protein complex assembly and membrane deformation. During early stages of mitotic NPC assembly, a seed for new NPCs is established on chromatin, yet the factors connecting the NPC seed to the membrane of the forming nuclear envelope are unknown. Here, we report that the reticulon homology domain protein REEP4 not only localizes to high-curvature membrane of the cytoplasmic endoplasmic reticulum but is also recruited to the inner nuclear membrane by the NPC biogenesis factor ELYS. This ELYS-recruited pool of REEP4 promotes NPC assembly and appears to be particularly important for NPC formation during mitosis. These findings suggest a role for REEP4 in coordinating nuclear envelope reformation with mitotic NPC biogenesis.     

Photoaffinity labeling of plasma membrane receptors for aldosterone from human mononuclear leukocytes.

Non-genomic effects of aldosterone on the sodium-proton-antiport have been shown in human mononuclear leukocytes which could be related to a new aldosterone membrane receptor. In the present paper plasma membranes from human mononuclear leukocytes were covalently photolabeled with a [125I]-aldosterone derivative. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed significant aldosterone binding at a molecular weight of approximately 50000 Dalton which was absent with 1 microM cold aldosterone, but not cortisol in the binding media. The presence of the sulfhydryl agent dithiothreitol did not affect results suggesting the absence of disulfide bridges in the steroid binding domain of the receptor. These data are the first to define the molecular weight of the membrane receptor for aldosterone.     

Microorganisms isolated from the bile of the patients who have undergone cholecystectomy and their antibiotic resistance pattern: multicenter prospective study

International Microbiology - Gallbladder and biliary tract infections are diseases with high mortality rates if they are not treated properly. Microbiological evaluation of perioperatively...     

A study on the determination of risk factors associated with babesiosis and prevalence of Babesia sp., by PCR amplification, in small ruminants from Southern Punjab (Pakistan)

Babesiosis is a parasitic infection due to the multiplication of tick borne parasite, Babesia sp., in erythrocytes of host, which includes a wide variety of vertebrates including small ruminants causing decreased livestock output and hence economic losses. The objective of the present study was to establish a PCR based method for the detection of Babesia sp. in small ruminant population in Southern Punjab and to determine the risk factors involve in the spread of babesiosis. A total of 107 blood samples were collected from 40 sheep and 67 goats in seven districts of Southern Punjab from randomly selected herds. Data on the characteristics of the animals and the herd were collected through questionnaires. 36 blood samples (34% of total) produced the DNA fragment specific for 18S rRNA gene of Babesia sp., by PCR amplification, of which 20 were sheep and 16 were goats. Samples from all seven district contained Babesia positive samples and prevalence varied between 18 to 68%. It was observed that male animals (P = 0.009) and young animals under one year of age (P = 0.01) were more prone to the parasite. It was observed that herds consist of more than 15 animals (P = 0.007), composed of mixed species of small ruminants (P = 0.022), associated with dogs (P = 0.003) and dogs having ticks on their bodies (P = 0.011) were among the major risk factors for the spread of babesiosis in small ruminants.     

Neuroprotective effect of combination therapy of glatiramer acetate and epigallocatechin-3-gallate in neuroinflammation

Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system. However, studies of MS and the animal model, experimental autoimmune encephalomyelitis (EAE), indicate that neuronal pathology is the principle cause of clinical disability. Thus, there is need to develop new therapeutic strategies that not only address immunomodulation but also neuroprotection. Here we show that the combination therapy of Glatiramer acetate (GA), an immunomodulatory MS therapeutic, and the neuroprotectant epigallocatechin-3-gallate (EGCG), the main phenol in green tea, have synergistic protective effects in vitro and in the EAE model. EGCG and GA together led to increased protection from glutamate- and TRAIL-induced neuronal cell death in vitro. EGCG combined with GA induced regeneration of hippocampal axons in an outgrowth assay. The combined application of EGCG and GA did not result in unexpected adverse events in vivo. Neuroprotective and neuroregenerative effects could be translated in the in vivo model, where combination treatment with EGCG and GA significantly delayed disease onset, strongly reduced clinical severity, even after onset of symptoms and reduced inflammatory infiltrates. These results illustrate the promise of combining neuroprotective and anti-inflammatory treatments and strengthen the prospects of EGCG as an adjunct therapy for neuroinflammatory and neurodegenerative diseases.