Diel timing of nest predation changes across breeding season in a subtropical shorebird

Predation is the most common cause of nest failure in birds. While nest predation is relatively well studied in general, our knowledge is unevenly distributed across the globe and taxa, with, for example, limited information on shorebirds breeding in subtropics. Importantly, we know fairly little about the timing of predation within a day. Here, we followed 444 nests of the red‐wattled lapwing (Vanellus indicus), a ground‐nesting shorebird, for a sum of 7,828 days to estimate a nest predation rate, and continuously monitored 230 of these nests for a sum of 2,779 days to reveal how the timing of predation changes over the day and season in a subtropical desert. We found that 312 nests (70%) hatched, 76 nests (17%) were predated, 23 (5%) failed for other reasons, and 33 (7%) had an unknown fate. Daily predation rate was 0.95% (95%CrI: 0.76% – 1.19%), which for a 30‐day long incubation period translates into ~25% (20% – 30%) chance of nest being predated. Such a predation rate is low compared to most other avian species. Predation events (N = 25) were evenly distributed across day and night, with a tendency for increased predation around sunrise, and evenly distributed also across the season, although night predation was more common later in the season, perhaps because predators reduce their activity during daylight to avoid extreme heat. Indeed, nests were never predated when midday ground temperatures exceeded 45℃. Whether the diel activity pattern of resident predators undeniably changes across the breeding season and whether the described predation patterns hold for other populations, species, and geographical regions await future investigations.     

Cytokines as potential combination agents with PD-1/PD-L1 blockade for cancer treatment

Immunotherapy has caused a paradigm shift in the treatment of several malignancies, particularly the blockade of programmed death-1 (PD-1) and its specific receptor/ligand PD-L1 that have revolutionized the treatment of a variety of malignancies, but significant durable responses only occur in a small percentage of patients, and other patients failed to respond to the treatment. Even those who initially respond can ultimately relapse despite maintenance treatment, there is considerable potential for synergistic combinations of immunotherapy and chemotherapy agents with immune checkpoint inhibitors into conventional cancer treatments. The clinical experience in the use of cytokines in the clinical setting indicated the efficiency of cytokine therapy in cancer immunotherapy. Combinational approaches to enhancing PD-L1/PD-1 pathways blockade efficacy with several cytokines such as interleukin (IL)-2, IL-15, IL-21, IL-12, IL-10, and interferon-α (IFN-α) may result in additional benefits. In this review, the current state of knowledge about PD-1/PD-L1 inhibitors, the date in the literature to ascertain the combination of anti-PD-1/PD-L1 antibodies with cytokines is discussed. Finally, it is noteworthy that novel therapeutic approaches based on the efficient combination of recombinant cytokines with the PD-L1/PD-1 blockade therapy can enhance antitumor immune responses against various malignancies.     

P53 protein and Ki-67 expression in chronic gastritis patients with positive Helicobacter pylori infection

The present study was carried out to assess the predictive value and expression of the proliferative activity of Ki-67 and the expression of p53 protein in Helicobacter pylori associated chronic gastritis. This study comprised archival blocks from 20 dyspeptic patients who at National Hepatology and Tropical Medicine Research Institute underwent a diagnostic oesophago-gastroduodenoscopy with multiple gastric antral endoscopic biopsies for histological examination. The blocks were cut at 5 nM thicknesses, stained by hematoxylin and eosin to score the inflammatory grade and subjected to Giemsa stain to assess H. pylori infection, and then immune–histochemical method was done to determine protein P53 and Ki-67. The obtained results indicated that there was no significant association between the expression of Ki67 and P53 in the studied cases. There was no significant association between Ki67 and P53 in the presence of intestinal atrophy, intestinal metaplasia, intestinal activity and intestinal inflammation. While, there was significant association between Ki67 and P53 in intestinal dysplasia, P = 0.015, 0.025, respectively. It could be concluded that the significant association of the proliferative marker Ki-67 and apoptotic marker p53 protein with intestinal dysplasia may be one of the main predictive values in the development of gastric carcinoma in patients with gastritis secondary to H. pylori infection.     

A possible therapy by juvenile hormone I to Spodoptera littoralis (Boisd.) larvae previously treated by precocene II

An effective constant dose (55 μg) of precocene II (PII) was topically tested against the last three instars of Spodoptera littoralis (Boisd.) larvae. Application of PII induced morphogenetic abnormalities typical of juvenile hormone (JH) excess. The resultant imperfect insects included larval‐pupal mosaic and partial or severe cases of untanned pupae. The sixth‐instar larvae were more sensitive to PII administration than the two preceding instars. However, sensitivity of the last larval instar to PII varied with the timing of dose application relative to the developmental status of the larvae. Whereas the newly ecdysed (0‐day old) larvae were more sensitive, the older larvae of the same sixth‐instar showed sharp decrease in their sensitivity to PII with a concomitant increase of their age. Application of a single dose (5 μg) of JH I to PII pre‐treated larvae significantly (P < 0.001) reduced the production of imperfect insects where many PH‐treated larvae developed successfully to apparent normal pupae. Although a single dose of PII was more effective on S. littoralis larvae than repeated daily doses, the effectiveness of JHI‐therapy to PH pre‐treated larvae by repeated doses was less effective in producing perfect insects than JH‐therapy to PII pre‐treated larvae by single doses. The reversal of any of these by applied JHI is quite interesting but the mechanisms remain to be unraveled.     

Comparison of botulinum toxin type A and aprotinin monotherapy with combination therapy in healing of burn wounds in an animal model

Burns are one of the most common injuries that are complicated by many challenges including infection, severe inflammatory response, excessive expression of proteases, and scar formation. The aim of this study was to investigate the effect of botulinum toxin type A (BO) and aprotinin (AP) separately or in combination (BO-AP) in healing process. Four burn wounds were created in each rat and randomly filled with silver sulfadiazine (SSD), BO, AP and BO-AP. The rats were euthanized after 7, 14, and 28 days, and their harvested wound samples were evaluated by gross pathology, histopathology, gene expression, biochemical testing, and scanning electron microscopy. Both BO and AP significantly reduced expression of interleukin-1β (IL-1β) and transforming growth factor-β1 (TGF-β1) at the 7th post wounding day. Moreover, they inhibited scar formation by reducing the TGF-β1 level and increasing basic fibroblast growth factor (bFGF) at the 28th day. AP by decreasing protease production showed more effective role than BO in wound regeneration. AP increased tissue organization and maturation and improved cosmetic appearance of wounds, at 28 days. The best results gained when combination of BO and AP were used in healing of burn wounds. Treatment by BO-AP significantly subsided inflammation compared to the BO, AP, and SSD treated wounds. Treatment with BO-AP also reduced collagen density and led to minimal scar formation. Combination of botulinum toxin type A and aprotinin considerably increased structural and functional properties of the healing wounds by reducing scar formation and decreasing production of proteases.

     

An anti-inflammatory role for carbon monoxide and heme oxygenase-1 in chronic Th2-mediated murine colitis

Cigarette smoking is a significant environmental factor in the human inflammatory bowel diseases, remarkably, conferring protection in ulcerative colitis. We previously demonstrated that a prominent component of cigarette smoke, CO, suppresses Th17-mediated experimental colitis in IL-10(-/-) mice through a heme oxygenase (HO)-1-dependent pathway. In this study, homeostatic and therapeutic effects of CO and HO-1 were determined in chronic colonic inflammation in TCR-α-deficient ((-/-)) mice, in which colitis is mediated by Th2 cytokines, similar to the cytokine milieu described in human ulcerative colitis. TCRα(-/-) mice exposed to CO or treated with the pharmacologic HO-1 inducer cobalt protoporphyrin demonstrated amelioration of active colitis. CO and cobalt protoporphyrin suppressed colonic IL-1β, TNF, and IL-4 production, whereas IL-10 protein secretion was increased. CO induced IL-10 expression in macrophages and in vivo through an HO-1-dependent pathway. Bacterial products regulate HO-1 expression in macrophages through MyD88- and IL-10-dependent pathways. CO exposure and pharmacologic HO-1 induction in vivo resulted in increased expression of HO-1 and IL-10 in CD11b(+) lamina propria mononuclear cells. Moreover, induction of the IL-10 family member IL-22 was demonstrated in CD11b(-) lamina propria mononuclear cells. In conclusion, CO and HO-1 induction ameliorated active colitis in TCRα(-/-) mice, and therapeutic effects correlated with induction of IL-10. This study provides further evidence that HO-1 mediates an important homeostatic pathway with pleiotropic anti-inflammatory effects in different experimental models of colitis and that targeting HO-1, therefore, is a potential therapeutic strategy in human inflammatory bowel diseases.     

Retrospective analysis of reconstruction techniques after periocular basalioma excision

The paper presents our approach to reconstruction after periocular basalioma (pBCC) excision, especially of large lower lid (LL) and medial canthal (MC) pBCC. Retrospective analysis of data of 123 patients with pBCC, confirmed on histologic examination (HE), operated in period from 1998 to 2006, was performed. Oncologic safety margins of 3 mm were marked after local anesthesia was administered. Reconstruction was done in time of surgery. In pBCC away from a lid margin, adjacent myocutaneous flaps were used. For lid margin involving (LM) pBCC, size of 10 mm and less in horizontal diameter (HD), full-thickness lid excision was performed, combined with lateral canthotomy and/or Tenzel or McGregor flap. When size of LM pBCC was more than 10 mm in HD and it was on a LL, ipsilateral upper lid (UL) tarsoconjunctival (TC) graft combined with single pedicle transposition myocutaneous flap were used. The same size of LM pBCC on a UL required ipsilateral full-thickness LL "switch" flap and/or contralateral LL Hübner graft. In MC pBCC combined approach was used. The follow-up was up to 5 years. The 19 patients (15.4%) had positive tumor margin on HE. Five of them refused further surgery, but only two had recurrence. The rest of 121 patients had no recurrence during follow-up. In 5/14 patients, who underwent additional surgery, no tumor cells were found on HE. The 10/123 patients (8.1%) had complications. The imperative of our approach to reconstruction after pBCC was good functional and cosmetic result, avoiding prolonged lid closure. Accordingly, in large LL LM pBCC we used ipsilateral UL TC graft combined with single pedicle transposition myocutaneous flap. In MC pBCC combined approach was mandatory.     

Role of histone modification and DNA methylation in signaling pathways involved in diabetic retinopathy

Retinopathy, characterized by an alteration of the retinal microvasculature, is a common complication of diabetes mellitus. These changes can cause increased permeability and alter endothelial cell proliferation, edema, and abnormal neovascularization and eventually result in blindness. The pathogenesis of diabetic retinopathy (DR) is complicated, involving many factors/mediators such as genetic susceptibility, microRNAs, and cytokines. One of the factors involved in DR pathogenesis is epigenetic changes that can have a key role in the regulation of gene expression; these include microRNAs, histone modifications, and methylation of DNA. The main epigenetic modifications are DNA methylation and posttranslational modifications of the histones. Generally, the studies on epigenetics can provide new opportunities to investigate the molecular basis of diseases with complicated pathogenesis, including DR, and provide essential insights into the potential design of strategies for its treatment. The aim of this study is an investigation of DR pathogenesis and epigenetic modifications that involve in DR development.     

Kefir Accelerates Burn Wound Healing Through Inducing Fibroblast Cell Migration In Vitro and Modulating the Expression of IL-1ß, TGF-ß1, and bFGF Genes In Vivo

Probiotics and Antimicrobial Proteins - Kefir is a natural probiotic compound with a long history of health benefits which can improve wound healing. This study investigated the regeneration...