Protective Oral Vaccination against Infectious bursal disease virus Using the Major Viral Antigenic Protein VP2 Produced in Pichia pastoris

Infectious bursal disease virus (IBDV) causes economically important immunosuppressive disease in young chickens. The self-assembling capsid protein (VP2) from IBDV strain IR01 was expressed in Pichia pastoris resulting in the formation of homomeric, 23-nm infectious bursal disease subviral particles (IBD-SVPs) with a yield of 76 mg/l before and 38 mg/l after purification. Anti-IBDV antibodies were detected in chickens injected with purified IBD-SVPs or fed with either purified IBD-SVPs or inactivated P. pastoris cells containing IBD-VP2 (cell-encapsulated). Challenge studies using the heterologous classical IBDV strain (MB3) showed that intramuscular vaccination with 20 µg purified IBD-SVPs conferred full protection, achieved complete virus clearance and prevented bursal damage and atrophy, compared with only 40% protection, 0–10% virus clearance accompanied by severe atrophy and substantial bursal damage in mock-vaccinated and challenge controls. The commercial IBDV vaccine also conferred full protection and achieved complete virus clearance, albeit with partial bursal atrophy. Oral administration of 500 µg purified IBD-SVPs with and without adjuvant conferred 100% protection but achieved only 60% virus clearance with adjuvant and none without it. Moderate bursal damage was observed in both cases but the inclusion of adjuvant resulted in bursal atrophy similar to that observed with live-attenuated vaccine and parenteral administration of 20 µg purified IBD-SVPs. The oral administration of 250 mg P. pastoris cells containing IBD-VP2 resulted in 100% protection with adjuvant and 60% without, accompanied by moderate bursal damage and atrophy in both groups, whereas 25 mg P. pastoris cells containing IBD-VP2 resulted in 90–100% protection with moderate bursal lesions and severe atrophy. Finally, the oral delivery of 50 µg purified IBD-SVPs achieved 40–60% protection with severe bursal lesions and atrophy. Both oral and parenteral administration of yeast-derived IBD-VP2 can therefore induce a specific and protective immune response against IBDV without affecting the growth rate of chickens.     

Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n=7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P<0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact, ghrelin balanced Bax/Bcl-2 ratio toward at increase of Bax level in the spermatocytes and therefore may stimulate apoptosis in these germ cells. In contrast, ghrelin administration significantly suppressed proliferation-associated peptide PCNA in the spermatocytes as well as spermatogonia (P<0.05). Whereas, caspase-3 activity did not show any marked alteration during the experiment in both groups (P>0.05). Upstream of Bax substance parallel to down-regulation of PCNA demonstrate that ghrelin may prevent massive accumulation of germ cells during normal spermatogenesis. These observations also indicate that ghrelin may be considered as a modulator of spermatogenesis in normal adult rats and could be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors.     

Optimization of TaDREB3 gene expression in transgenic barley using cold‐inducible promoters

Constitutive over‐expression of the TaDREB3 gene in barley improved frost tolerance of transgenic plants at the vegetative stage of plant development, but leads to stunted phenotypes and 3‐ to 6‐week delays in flowering compared to control plants. In this work, two cold‐inducible promoters with contrasting properties, the WRKY71 gene promoter from rice and the Cor39 gene promoter from durum wheat, were applied to optimize expression of TaDREB3. The aim of the work was to increase plant frost tolerance and to decrease or prevent negative developmental phenotypes observed during constitutive expression of TaDREB3. The OsWRKY71 and TdCor39 promoters had low‐to‐moderate basal activity and were activated by cold treatment in leaves, stems and developing spikes of transgenic barley and rice. Expression of the TaDREB3 gene, driven by either of the tested promoters, led to a significant improvement in frost tolerance. The presence of the functional TaDREB3 protein in transgenic plants was confirmed by the detection of strong up‐regulation of cold‐responsive target genes. The OsWRKY71 promoter–driven TaDREB3 provides stronger activation of the same target genes than the TdCor39 promoter. Analysis of the development of transgenic plants in the absence of stress revealed small or no differences in plant characteristics and grain yield compared with wild‐type plants. The WRKY71–TaDREB3 promoter–transgene combination appears to be a promising tool for the enhancement of cold and frost tolerance in crop plants but field evaluation will be needed to confirm that negative development phenotypes have been controlled.     

Mechanism of the Bell-Shaped Profile of Ribonuclease A activity: Molecular Dynamic Approach

Ribonuclease-A is a small enzyme contains an active site with positive charges for its substrate. His¹² and His¹¹⁹ of its active site play critical role in enzyme catalysis. Salts show a bell-shaped profile on enzyme activity with an optimum salt concentration of about 0.1?M for optimum activity. The mechanism of decreased activity of the enzyme at low salt concentrations is not clear. In this work, we made a new effort to study the molecular events causing inactivation of RNase-A at low concentrations of NaCl. Our molecular dynamic result confirms that decrease in salt concentrations below an optimal level leads to an enzyme structure with lower dynamism and flexibility than that needed for optimum activity.     

Abdominal pain as presentation of Takayasu's arteritis in an adolescent male patient

We describe a boy with chronic abdominal pain, nausea and vomiting, and weight loss. The imaging was compatible with Takayasu's arteritis. Chronic mesenteric ischemia was the etiology of the patient's symptoms.     

New trends in glioma cancer therapy: Targeting Na+/H+ exchangers

Glioma is the oneof the most prevalent primarybrain tumors. There is a variety of oxidative stresses, inflammatory pathways, apoptosis signaling, and Na⁺/H ⁺ exchangers (NHEs) involved in the pathophysiology of glioma. Previous studies have indicated a relationship between NHEs and some molecular pathways in glioma. NHEs, including NHE1, NHE5, and NHE9 affect apoptosis, tumor-associated macrophage inflammatory pathways, matrix metalloproteinases, cancer-cell growth, invasion, and migration of glioma. Also, inhibition of NHEs contributes to increased survival in animal models of glioma. Limited studies, however, have assessed the relationship between NHEs and molecular pathways in glioma. This review summarizes current knowledge and evidence regarding the relationship between NHEs and glioma, and the mechanisms involved.     

Aquaporin 4: A key player in Parkinson's disease

Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases which occur in aged people worldwide. Given that a sequence of cellular and molecular mechanisms, including oxidative stresses, apoptosis, inflammatory pathways, microglia, astrocyte activation, and aquaporin 4 (AQP4) are associated with initiation and the progression of PD. AQP4 may affect various pathways (i.e., α-synuclein, inflammatory pathways, and microglia and astrocyte activation). Few reports have evaluated the relationship between AQP4 and PD-related cellular and molecular pathways. Here, for the first time, we highlighted the relationship between AQP4 and molecular mechanisms involved in PD pathogenesis.     

Evidence of curcumin and curcumin analogue effects in skin diseases: A narrative review

Curcumin, a natural polyphenolic and yellow pigment obtained from the spice turmeric, has strong antioxidative, anti-inflammatory, and antibacterial properties. Due to these properties, curcumin has been used as a remedy for the prevention and treatment of skin aging and disorders such as psoriasis, infection, acne, skin inflammation, and skin cancer. Curcumin has protective effects against skin damage caused by chronic ultraviolet B radiation. One of the challenges in maximizing the therapeutic potential of curcumin is its low bioavailability, limited aqueous solubility, and chemical instability. In this regard, the present review is focused on recent studies concerning the use of curcumin for the treatment of skin diseases, as well as offering new and efficient strategies to optimize its pharmacokinetic profile and increase its bioavailability.     

Cell competition: Winning out by losing notch

Cell competition where ‘loser’ cells are eliminated by neighbors with higher fitness is a widespread phenomenon in development. However, a growing body of evidence argues cells with somatic mutations compete with their wild type counterparts in the earliest stages of cancer development. Recent studies have begun to shed light on the molecular and cellular mechanisms that alter the competitiveness of cells carrying somatic mutations in adult tissues. Cells with a ‘winner’ phenotype create clones which may expand into extensive fields of mutant cells within normal appearing epithelium, favoring the accumulation of further genetic alterations and the evolution of cancer. Here we focus on how mutations which disrupt the Notch signaling pathway confer a ‘super competitor’ status on cells in squamous epithelia and consider the broader implications for cancer evolution.