Restrategizing becomes inevitable when in trying to proffer solution to a problem, damage in a different form is done. The unintended effects of drugs (side effects) could be leaving behind more damage than the therapeutic effect they are required to provide. This has led to the withdrawal of a number of drugs. However, there are still a number of options to explore in delivery, especially in the application of nanomedicine. Such advances in nanomedicine employ the use of phenylboronic acid-installed polymeric micelles, matrix metalloproteinase 2-sensitive poly(ethylene glycol)-drug conjugate, multifunctional DNA nanoflowers, single vehicular delivery of small interfering RNA (siRNA), nanoparticle-mediated codelivery of siRNA and prodrug, lipopeptide nanoparticles for siRNA delivery, ferrous iron-dependent drug delivery, polyprodrug amphiphiles, transepithelial transport of Fc-targeted nanoparticles, mutant KRAS target, monovalent molecular shuttle, near-infrared-actuated devices, transferrin receptor trafficking, remote loading of preencapsulated drugs, ATP-mediated liposomal drug delivery, nanoparticle-based combination chemotherapy delivery system, nucleic acid nanoparticle conjugates, ultrasound-triggered disruption of cross-linked hydrogels, refilling drug delivery depots through the blood, siRNA payloads to target KRAS-mutant cancer, delivery of antibody mimics into mammalian cells, biologically “smart” hydrogel, combination of liposomes containing bio-enhancers, and tetraether lipids. Minimized side effects, increased bioavailability, and reduced dosage are possible benefits of improved drug targeting.
Ischemia-reperfusion injury is a urological emergency condition that could lead to necrosis, testicular damage subfertility, and infertility. The purpose of this study was to identify changes taking place in the rat testis at short-term (4 hr) as well as long-term (7 days) reperfusion following testicular torsion and to evaluate the effects of Proxeed Plus (PP), L-carnitine-rich antioxidant supplement, on preventing these changes using the biochemical parameters and histopathology. Thirty adult male rats were divided into five groups: in groups, 1-4 testicular ischemia was achieved by rotating the left testis 720° clockwise for 4 h and dividing into the sham, torsion/detorsion (T/D), T/D+1000 mg/kg BW PP, and T/D+5000 mg/kg BW PP groups, respectively. PP was administered intraperitoneally 30 min before detorsion while group 5 served as the normal control. All rats were sacrificed 4 h after detorsion. The same experimental design was set up, and animals were sacrificed after 7 days of detorsion. The testicular levels of human cyclooxygenase-2; tumor necrosis factor; interleukins-1β, 6, and 10; hydrogen peroxide; malonaldehyde; superoxide dismutase; catalase; glutathione transferase; glutathione peroxidase; glutathione reductase; and histopathological damage were evaluated. Our results revealed that rats in the torsion/detorsion group exhibited elevated testicular levels of oxidative markers and proinflammatory cytokines, low levels of antioxidant enzymes, and severe histological alterations relative to the control and sham groups. Treatments with 1000 and 5000 mg/kg BW of PP for 4 hr and 7 days significantly ( p < 0.05 ) decreased the levels of the proinflammatory and oxidative markers while increasing the spermatogenesis, testicular levels of antioxidant enzymes, and anti-inflammatory cytokine (IL-10) in a dose-dependent manner. This suggested that PP exhibited anti-inflammatory and antioxidant activities against I/R testes thus serving as an effective supplement to protect against testicular assault.
Corchorus olitorius is a common vegetable in Nigeria used in making soup and stew. This study determined the effect of the ethanol extract of C. olitorius leaves on the activity of liver function enzymes and lipid profiles in Wistar albino rats. Twenty four (24) Wistar rats weighing between 150-200 g were randomly grouped into four of six animals each. Groups 1-3 rats received 2 ml 50, 100 and 200 mg/kg b.w. respectively, while the control group also received 2ml of distilled water orally for the period of the experiment. All animals were sacrificed after experimental period of 28 days. The results showed that the extract significantly (p=0.05) reduced the serum activities of AST, ALT and ALP when compared to the control at all doses tested. Also, the extract significantly reduced the concentration of total cholesterol at 50 and 100 mg/kg b.w. of the ethanol extract of C. olitorius and significantly (p=0.05) increased it at 200mg when compared to the control. A dose dependent significant (p=0.05) increase in the concentration of HDL and triacylglycerol were observed in all groups when compared to the control. The result of this study suggests that the ethanol extract of C. olitorius possesses hepatoprotective properties with possible tendency to increase the cholesterol concentrations at high doses.
Although almost all biological processes are mediated by a variety of proteins, it is important to bring to spotlight recent experimental and clinical research advances that had their focus on highlighting and taking advantage of the roles of several strategic proteins in order to gain more understanding of cancer biology. Proteins have a major stake in the initiation, progression, sustenance and completion of cellular processes, and have also demonstrated their vital roles in cancer processes. The characteristic functions of proteins and modified proteins have been utilized in the understanding and treatment of cancer. Recent insights in such roles and applications include linker histone H1.2 in the compaction of chromatin and gene silencing via the recognition of H3K27me3; c-Jun with Fra-2/c-Fos in the promotion of aggressive tumour phenotypes in tongue cancer; the use of sodium channelinhibiting agents targeting the transmembrane protein in breast, colon and prostate cancer; SET-mediated activities; protein interaction networks in glioma; Gpnmb significance as a biomarker; β-carbolines inhibition on Wnt/β-catenin signaling; p53 mutants co-opt chromatin pathways; Bone morphogenetic protein 4 as regulator of the behaviors of cancer cell; Brain-Expressed X-linked (BEX) proteins in human cancers; targeting CDK4/6 including protein kinases to make a reversal of multidrug resistance in sarcoma. In-depth knowledge of Proteomics will go a long way in helping us uncover a lot more strategies that will help us in the long fight against cancer.
BACKGROUND Typhoid fever resistance is on the increase and this frustrates efforts at treatment. Persistence of multiple drug-resistant (MDR) typhoid fever leads to higher mortality rate since treatment is evasive. OBJECTIVE This study intended to identify if liver enzymes and lactate levels are related to aggravating MDR in patients diagnosed with typhoid fever. METHODS 50 subjects were recruited, 45 were positive for Widal test and further subjected to stool culture examination for the presence of S. Typhi. All subjects blood were analysed for lactate, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) RESULTS Growth of S. Typhi was observed in only eight subjects out of the 45 Widal positive test subjects. The eight positive S. Typhi isolates showed resistance to the first line drugs, macrolides and 3rd generation cephalosporins but showed susceptibility to fluoroquinolones. ALP, AST, ALT and blood lactate were elevated in all multi-drug resistant patients. Highest levels of liver enzymes were observed in subjects resistant to the greatest number of antibiotics. However, there was no significant correlation of increase in blood lactate level and ALP when compared with increase in resistance based on number of antibiotics (R2=0.2858, R2=0.4675). CONCLUSIONS Lactate and liver enzyme levels increase markedly during typhoid fever infection, however in MDR scenario, especially in resistance to different classes of antibiotics, the metabolic toll on the liver increases and is reflected in elevation of AST and ALT. Keywords: Antibiotics, liver enzymes, lactate, typhoid fever, multiple drug resistance
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