Studies using inhibitors that reportedly discriminate between cathepsin B and related lysosomal cysteine proteinases have implicated the enzyme in a wide range of physiological and pathological processes. The most popular substance to selectively inhibit cathepsin B in vivo is CA-074Me, the methyl ester of the E-64 derivative CA-074. However, we now have found that CA-074Me inactivates both cathepsin B and cathepsin L within murine fibroblasts. In contrast, exposure of these cells to the parental compound CA-074 leads to the selective inhibition of endogenous cathepsin B, while intracellular cathepsin L remains unaffected. These results indicate that CA-074 rather than CA-074Me should be used to specifically inactivate cathepsin B within living cells.

Synbiotic (SYN) additives were assessed as an antibiotic alternative on the effects on the nonspecific immune response and disease resistance of O. niloticus to P. aeruginosa. Healthy fish (n = 120, average initial weight 18 ± 2 g) were allotted randomly into four experimental groups (3 replicates for each); 1) a control group with no additives (CON), 2) basal diet complemented with 0.1 g kg^–1 diets of norfloxacin, NFLX, 3) basal diet fortified with 1 mL kg^–1 diet of SYN, and 4) basal diet complemented with a mixture of NFLX and SYN, which was carried out for eight weeks. Results showed a significant increase (p < 0.01) in the serum immune parameters (total protein, globulin and albumin, nitric oxide (NO), and lysozyme activity) in the SYN group and the NFLX+SYN group compared with the CON and NFLX groups. The serum glucose, cholesterol, and triglycerides were higher in NFLX and NFLX+SYN groups than the CON and SYN groups. The catalase (CAT), superoxide dismutase, glutathione peroxidase (GPX) activities were significantly augmented in the NFLX+SYN group, followed by the SYN group compared with CON and NFLX groups. The cumulative mortality rate (CMR) of O. niloticus following the P. aeruginosa challenge was decreased in the SYN group compared to other groups. The results emphasize that synbiotic could be used as a norfloxacin alternative to enhance the related immunological parameters, including antioxidant activity and disease resistance against P. aeruginosa infection of O. niloticus.

O1 Regulation of genes by telomere length over long distances

The influences of Boswellia serrata resin extract (BSRE) as a feed additive on the growth performance, immune response, antioxidant status, and disease resistance of Nile tilapia, Oreochromis niloticus L. were assessed. One hundred-forty four fingerlings (initial weight: 21.82 ± 0.48 g) were randomly allotted into four groups with three replicates where they were fed on one of four treatments with four levels of Boswellia serrata resin extract 0, 5, 10, or 15 g kg⁻¹, BSRE0, BSRE5, BSRE10, BSRE15, respectively for eight weeks. After the end of the feeding trial, the fish were challenged with Staphylococcus aureus, and mortalities were noted. The final body weight, total body weight gain, and the total feed intake were quadratically increased in BSRE5 treatment (p < 0.01). The protein productive efficiency (PPE) was linearly and quadratically increased in all BSRE supplemented treatments (p < 0.01). Dietary addition of BSRE raised the fish crude protein content and reduced the fat content in a level-dependent manner (p < 0.01). The ash content was raised in the BSRE15 group (p < 0.01). Dietary BSRE supplementation decreased the serum levels of glucose, total cholesterol, triglycerides, and nitric oxide. It increased the serum levels of total protein, albumin, total globulins, α1 globulin, α2 globulin, ß globulin, ɣ globulin, Catalase, and SOD (superoxide dismutase) activity, GSH (reduced glutathione), lysozyme activity, and MPO (myeloperoxidase) in a level-dependent manner (p < 0.05). The BSRE15 diet increased the serum level of ALT (alanine aminotransferase) and decreased creatinine serum level (p < 0.05). Dietary BSRE supplementation increased the relative percentage of survival % (RPS) of S. aureus challenged fish. The histoarchitecture of the gills and kidney was normal in the BSRE5 treatment and moderately changed in BSRE10 and BSRE15 treatments. The splenic lymphoid elements were more prevalent, and the melano-macrophage centers (MMC) were mild to somewhat activated in BSRE supplemented treatments. Dietary BSRE supplementation improved the intestinal histomorphology. It can be concluded that BSRE addition can enhance the antioxidant activity, immune status, and disease resistance of O. niloticus to S. aureus infection. The level of 5 g kg⁻¹ BSRE can improve fish growth without causing harmful effects on fish health. The highest levels of BSRE are not recommended as they badly affected the histoarchitecture of many vital organs.

Cisplatin (Cis) a drug commonly used as a chemotherapeutic agent to treat various types of cancer, inducing testicular damage. The present study aimed to investigate the inhibitory potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) and beetroot extract (BRE) in albino rats after testicular toxicity induced by cisplatin. Thirty adult male albino rats were grouped into: the control group, Cis group receiving a single dose of 7 mg/kg i.p. (intraperitoneal) to induce testicular toxicity, Cis plus BM-MSCs injected Cis followed by 2 × 10⁶ of BM-MSCs; Cis plus BRE group receiving Cis followed by 300 mg/kg body weight/day of BRE, and Cis plus BM-MSCs and BRE group. In the current study, Cis reduced sperm count, serum testosterone level, and testicular activity of alkaline phosphatase (AKP), besides a marked inhibition of succinate dehydrogenase (SDH) activity. In addition, it significantly increased malondialdehyde (MDA) and along with a marked decrease in testis reduced glutathione content and total antioxidant capacity (TAC). At the same time, Cis administration resulted in a marked elevation in interleukine-6 and the iNOS and caspase-3 genes; however, it decreased the expression of steroidogenic acute regulatory protein (StAR). Combined treatment with BM-MSCs and BRE resulted in great improvement of all previous parameters. These results were also confirmed by histopathological and immunohistochemical examination. In conclusion, both MSCs and BRE were found to have potent potentials to inhibit testicular damage induced by cisplatin.