Brucellosis Causes Alteration in Trace Elements and Oxidative Stress Factors

Brucellosis is regarded as one of the most common diseases among humans and livestock. In the present study, we aimed to assess the effect of this disease on the level of various cations including copper (Cu), manganese (Mn), zinc (Zn), and magnesium (Mg) as well as oxidative stress status in the serum of people suffering from brucellosis. The present case-study was carried out on 40 patients with brucellosis (case) and 20 healthy people (control). Blood specimens were taken from all the people and the level of essential trace elements and oxidative stress status were measured. The serum level of copper in the case group (165.39 ± 43.19 μg/dl) was significantly higher compared with that in the control group (122.12 ± 28.88 μg/dl). Whereas the serum level of zinc was significantly lower in the case group compared with that in the control group (76.47 ± 28.88 vs. 92.85 ± 23.16 μg/dl). The manganese and magnesium serum levels did not differ significantly between the two groups. Furthermore, total antioxidant capacity level was significantly lower in the case group (122.12 ± 28.22 μmol/ml) than that in the control group (3.08 ± 0.12 μmol/ml) and the level of serum malondialdehyde was significantly higher in the case group (7.20 ± 0.23 mmol/ml) than that in the control group (4.0 ± 0.19 mmol/ml). Brucellosis can cause alteration in the serum level of essential trace elements. Moreover, the present study indicated that brucellosis produces oxidative stress in patients.     

Intraspecific killing among Leopards (Panthera pardus) in Iran (Mammalia: Felidae)

Intraspecific aggression is one of the most common causes of death in leopards. Here, we report four cases of intraspecific killing amongst Persian Leopards (Panthera pardus saxicolor) in Iran. A young male leopard was found on 7 June 2008 which, according to camera trap images, had been killed by an adult male over a Red Deer (Cervus elaphus) kill, with trauma to his neck in Dorfak No-Hunting Area. A young female that had been fitted with a satellite GPS collar on 6 December 2015 in Tandoureh National Park died on 29 January 2016 at a site where an Urial Sheep (Ovis orientalis) ram had been freshly killed. Necropsy results, footprints at the scene of death and camera trap footage all supported the deduction that the animal was killed by a larger female leopard at the kill site. On 13 January 2017, a young, partially eaten female leopard was found with double puncture on the side of her throat. Finally, a rehabilitated adult female fitted with a satellite GPS collar found on 19 December 2017 with a double puncture on her head with several trauma and haemorrhages on her back. These instances seem to be the first documented reports of intraspecific killing among free-ranging leopards in Asia.     

Predator–prey relationships in a middle Asian Montane steppe: Persian leopard versus urial wild sheep in Northeastern Iran

Management controversies arise when both of the prey and predator in an ecosystem are species of conservation concern. We investigated trophic interactions between the endangered Persian leopard (Panthera pardus saxicolor) and a declining mountain ungulate, urial wild sheep (Ovis vignei), on a high-altitude steppe of Iran. During two consecutive photo-trapping seasons of 1,300 nights in total, a minimum population of four adult leopards (one female and three males) was documented. Scat analysis indicated that urial wild sheep was the staple of the leopard diet with 48.44 % of total biomass consumed. Remains of domestic livestock in leopard scats were negligible yet alarming (14.53 % biomass consumed), followed by wild pigs (8.13 %) and wild goat (1.26 %). Financial costs of leopard depredation to livestock breeders during our study period were comparatively lower than livestock–leopard conflict hotspots across Iran. Using distance sampling, urial density was 15.8 individuals km^?2 (±SE 6.2), and a total biomass of 47,621.5 kg for wild ungulates in the study area was estimated. We estimated that the annual removal rate of urial by leopards during our study period was 9.4 % of the total urial population. We suggest that continuous monitoring of the leopard and prey populations to assess predation impact should be considered, particularly in areas where a single species comprises a remarkable proportion of the leopard diet. In the meantime, assessing probable conflicts with local communities is recommended as a parallel management action to ensure long-term human–leopard coexistence. Our findings will aid wildlife managers in prey-depleted arid environments of western Asia to identify susceptible wild prey populations to predation by large carnivores; hence, significantly contribute in development and implementation of effective conservation measures to mitigate management conflicts.     

Functions of family-22 carbohydrate-binding modules in Clostridium josui Xyn10A

Clostridium josui xylanase Xyn10A is a modular enzyme comprising two family-22 carbohydrate-binding modules (CBMs), a family-10 catalytic module (CM), a family-9 CBM, and two S-layer homologous modules, consecutively from the N-terminus. To study the functions of the family-22 CBMs, truncated derivatives of Xyn10A were constructed: a recombinant CM polypeptide (rCM), a family-22 CBM polypeptide (rCBM), and a polypeptide composed of the family-22 CBMs and CM (rCBM-CM). Recombinant proteins were characterized by enzyme and binding assays. rCBM-CM showed the highest activity toward xylan and weak activity toward some polysaccharides such as barley beta-glucan and carboxymethyl-cellulose. Although rCBM showed an affinity for insoluble and soluble xylan as well as barley beta-glucan and Avicel in qualitative binding assays, removal of the CBMs negligibly affected the catalytic activity and thermostability of the CM.     

Conversion of antibacterial quinolone drug levofloxacin to potent cytotoxic agents

Levofloxacin, the optical S-(-) isomer of ofloxacin, is a broad-spectrum antibacterial agent widely used to control various infections caused by Gram-positive and Gram-negative bacteria. While the COOH group is necessary for antibacterial activity, its modification can offer anticancer activity to the fluoroquinolone framework. Therefore, several levofloxacin carboxamides 11a-j and 12 containing 5-substituted-1,3,4-thiadiazole residue were synthesized and screened in vitro for their anticancer activity. The in vitro MTT viability assay revealed that the most compounds had significant activity against cancer cells MCF-7, A549, and SKOV3. In particular, the 3-chloro- and 4-fluoro- benzyl derivatives ( 11b and 11h ), with IC₅₀ values of 1.69–4.76 μM were as potent as or better than doxorubicin. It should be noted that the mother quinolone levofloxacin showed no activity on the tested cancer cell lines. The SAR analysis demonstrated that the 3-chloro or 4-fluoro substituent on the S-benzyl moiety had positive effect on the activity. Further in vitro evaluations of the most promising compounds 11b and 11h by flow cytometric analysis and comet test revealed the ability of compounds in the induction of apoptosis and blockage of the cell proliferation at the G1-phase by nuclear fragmentation and DNA degradation in cancer cells. The obtained results demonstrated that the alteration of 6-COOH functional group in the levofloxacin structure and conjugation with a proper heterocyclic pharmacophore is a good strategy to obtain new anticancer agents.     

Remote controlling of CAR-T cells and toxicity management: Molecular switches and next generation CARs

Cell-based immunotherapies have been selected for the front-line cancer treatment approaches. Among them, CAR-T cells have shown extraordinary effects in hematologic diseases including chemotherapy-resistant acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL). In this approach, autologous T cells isolated from the patient''s body genetically engineered to express a tumor specific synthetic receptor against a tumor antigen, then these cells expanded ex vivo and re-infusion back to the patient body. Recently, significant clinical response and high rates of complete remission of CAR T cell therapy in B-cell malignancies led to the approval of Kymriah and Yescarta (CD19-directed CAR-T cells) were by FDA for treatment of acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Despite promising therapeutic outcomes, CAR T cells also can elicit the immune-pathologic effects, such as Cytokine Release Syndrome (CRS), Tumor Lysis Syndrome (TLS), and on-target off-tumor toxicity, that hampered its application. Ineffective control of these highly potent synthetic cells causes discussed potentially life-threatening toxicities, so researchers have developed several mechanisms to remote control CAR T cells. In this paper, we briefly review the introduced toxicities of CAR-T cells, then describe currently existing control approaches and review their procedure, pros, and cons.     

Differential physiological and biochemical responses of Quercus infectoria and Q. libani to drought and charcoal disease

The vast oak-dominated forests of the Zagros Mountains in southwestern Iran currently undergo large-scale dieback driven by a combination of drought and increasing incidence of charcoal disease caused by the fungal pathogens Biscogniauxia mediterranea and Obolarina persica. Here, we explore the interactive effects between drought and charcoal disease agents on the physiology and biochemistry of Quercus infectoria and Quercus libani seedlings. The combination of pathogen attack and water limitation hampered plant development, especially in Q. libani seedlings, negatively affecting growth, biomass production, photosynthetic efficiency, and leaf water potential. An increase in markers of oxidative damage together with the upregulation of the antioxidant defense revealed that drought stress and pathogen infection led to pro-oxidative conditions in both oak species, especially in Q. libani, where larger changes in malondialdehyde and hydrogen peroxide occurred. The upregulation of the antioxidant system was more prominent in Q. infectoria than in Q. libani, resulting in enhanced enzyme activity and accumulation of non-enzymatic antioxidants. Fungal infection stimulated the activity of chitinase, phenylalanine ammonia lyase and β-1,3-glucanase in Q. infectoria leaves and this response became more pronounced under water shortage. Our study highlights that drought stress greatly intensifies the effects of the charcoal disease. Moreover, our findings imply superior stress resistance of Q. infectoria conferred by a highly efficient antioxidant system, strong osmotic adjustment (through proline), and increases in resistance enzymes and secondary metabolites (phenols and flavonoids). Future investigations should focus on adult trees in their natural habitat including interactions with soil factors and other pathogens like nematodes, bacteria and other fungi. Because the present research was conducted on oak seedlings, the findings can be considered by forest nursery managers.     

Optimization of Bacillus subtilis natto growth parameters in glycerol-based medium for vitamin K (Menaquinone-7) production in biofilm reactors

Bioprocess and Biosystems Engineering - Menaquinone-7 (MK-7) is the key form of vitamin K used as a dietary supplement and its production revolves around Bacillus subtilis natto. Current...     

Synthesis,structure–activity relationship and molecular docking of 3-oxoaurones and 3-thioaurones as acetylcholinesterase and butyrylcholinesterase inhibitors

The present study describes efficient and facile syntheses of varyingly substituted 3-thioaurones from the corresponding 3-oxoaurones using Lawesson’s reagent and phosphorous pentasulfide. In comparison, the latter methodology was proved more convenient, giving higher yields and required short and simple methodology. The structures of synthetic compounds were unambiguously elucidated by IR, MS and NMR spectroscopy. All synthetic compounds were screened for their inhibitory potential against in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Molecular docking studies were also performed in order to examine their binding interactions with AChE and BChE human proteins. Both studies revealed that some of these compounds were found to be good inhibitors against AChE and BChE.