Improved therapy for clear cell renal cell carcinoma: beta-hydroxybutyrate and quercetin target hypoxia-induced angiogenesis and multidrug resistance.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a form of kidney cancer characterized by dysregulated angiogenesis and multidrug resistance. Hypoxia-induced tumor progression plays a crucial role in ccRCC pathogenesis. Beta-hydroxybutyrate (BHB) and quercetin (QCT) have shown potential in targeting angiogenesis and drug resistance in various cancer types. This study investigates the combined effects of BHB and QCT in hypoxia-induced Caki-1 cells. METHODS: Caki-1 cells were subjected to normoxic and hypoxic conditions and treated with BHB, QCT, or a combination of both. Cell-viability was assessed using the MTT assay, and mRNA expression levels of key angiogenesis-related genes (HIF-1α/2α, VEGF, Ang-1, Ang-2, and MDR4) were quantified through real-time PCR during 24 and 48 h. RESULTS: BHB and QCT treatments, either alone or in combination, significantly reduced cell-viability in Caki-1 cells (p < 0.05). Moreover, the combined therapy demonstrated a potential effect in downregulating the expression of angiogenesis-related genes and MDR4 in hypoxia-induced cells, with a marked reduction in HIF-1α/2α, VEGF, Ang-1, and MDR4 expression (p < 0.05). The expression of Ang-2 increases significantly in presence of BHB combined QCT treatment. CONCLUSION: This study highlights the promising potential of a combination therapy involving BHB and QCT in mitigating angiogenesis and MDR4 expression in hypoxia-induced ccRCC cells. These findings support further investigation into the underlying mechanisms and warrant clinical studies to evaluate the therapeutic value of this combined treatment for ccRCC patients. This research provides new insights into addressing the challenges posed by angiogenesis and drug resistance in ccRCC.

Evaluating the incidence of ampC-ß-lactamase genes, biofilm formation, and antibiotic resistance among hypervirulent and classical Klebsiella pneumoniae strains.

AIM: Both immunocompetent and healthy individuals can become life-threateningly ill when exposed to the hypervirulent (hvKp) strains of Klebsiella pneumoniae (Kp). The main objectives of this study were to evaluate the presence of ampC-lactamase genes, biofilm formation, and antibiotic resistance in clinical strains of hvKp and cKp (classical K. pneumoniae). MATERIALS AND METHODS: Kp strains were collected from patients referred to Shahidzadeh Hospital in Behbahan City, Khuzestan Province, Iran. Several techniques were used to identify hvKp. The hypermucoviscosity phenotype was determined using the string test. Isolates that developed dark colonies on tellurite agar were assumed to be hvKp strains. If any of the iucA, iutA, or peg-344 genes were detected, the isolates were classified as hvKp. Phenotypic and genotypic detection of AmpC ß-lactamases of hvKp strains was performed by the combined disk method and polymerase chain reaction, respectively. In addition, crystal violet staining was used to determine the biofilm formation of these isolates. RESULTS: For this study, 76 non-duplicative isolates of Kp were collected. Overall, 22 (28.94%) strains had positive string test results, and 31 (40.78%) isolates were grown in tellurite-containing medium. The genes iucA and iutA or peg-344 were found in 23.68% of all Kp strains and in 50% of tellurite-resistant isolates, respectively. The most effective antibiotics against hvKp isolates were tetracycline (85.52%) and chloramphenicol (63.15%). Using the cefoxitin disc diffusion method, we observed that 56.57% (43/76) of the strains were AmpC producer. A total of 30.26% (n = 23/76) of the isolates tested positive for at least one ampC gene, including blaDHA (52.63%, n = 40), blaCIT (40.78%, n = 31), blaACC (19.76%, n = 15), blaMOX (25%, n = 19), and blaFOX (43.42%, n = 33). Biofilm formation analysis revealed that most hvKp isolates were weak (n = 6, 40%) and moderate (n = 5, 33.33%) biofilm producers. CONCLUSION: Healthcare practitioners should consider the possibility of the existence and acquisition of hvKp everywhere. The exact mechanisms of bacterial acquisition are also unknown, and it is unclear whether the occurrence of infections is related to healthcare or not. Thus, there are still many questions about hvKp that need to be investigated.

Bilirubin improves renal function by reversing the endoplasmic reticulum stress and inflammation in the kidneys of type 2 diabetic rats fed high-fat diet.

Diabetic kidney disease (DKD), as a chronic diabetes-induced complication, is considered the most frequent leading cause of end-stage renal disease (ESRD). Regarding the observed protective effects of bilirubin, as a potential endogenous antioxidant/anti-inflammatory compound, against DKD progression, we planned to evaluate the effects of bilirubin administration on endoplasmic reticulum (ER) stress and inflammation in type 2 diabetic (T2D) rats fed high-fat diet (HFD). In this regard, thirty 8-week adult male Sprague Dawley rats were divided into five groups (n = 6). T2D and obesity were induced by streptozotocin (STZ) (35 mg/kg) and HFD (700 kcal/day), respectively. Bilirubin treatment was carried out for 6- and 14-week intervals (10 mg/kg/day), intraperitoneally. Then, the expression levels of ER stress-related genes (i.e. binding immunoglobulin protein (Bip), C/EBP homologous protein (Chop), and spliced x-box-binding protein 1 (sXbp1), as well as nuclear factor-κB (NF-κB) were analyzed using quantitative Real-time PCR experiments. Moreover, histopathological and stereological changes of kidney and its related structures were investigated for the studied rats. Bip, Chop, and NF-κB expression levels were significantly decreased under bilirubin treatment, while sXbp1 was up-regulated following the bilirubin administration. More interestingly, glomerular constructive damages seen in HFD-T2D rats, were considerably improved in the animals received bilirubin. Stereological assessments also revealed that bilirubin could desirably reverse the mitigation of kidney's total volume and its related structures, such as cortex, glomeruli, and convoluted tubules. Taken together, bilirubin has potential protective/ameliorative effects on DKD progression, especially through alleviating the renal ER stress and inflammatory responses in T2D rats with injured kidneys. In this era, clinical benefits of mild hyperbilirubinemia can be considered in human DKD.

Facile synthesis of green and efficient magnetic nanocomposites of carrageenan/copper for the reduction of nitrophenol derivatives.

A green and facile method for preparation of Kappa-Carrageenan or Iota-Carrageenan grafted N,N'-methylenebisacrylamide/Fe3O4/Cu nanoparticles (κC-g-MBA/MNPs/Cu and ιC-g-MBA/MNPs/Cu) catalysts was developed to place copper on a magnetic carrageenan surface. The structure and morphology of the prepared catalysts were identified using FT-IR, XRD, BET, VSM, TGA, EDX, mapping, FE-SEM, TEM, and ICP-OES analyses. The catalytic activity of the catalysts was investigated to reduce 4-nitrophenol, 2-nitrophenol, 3-nitroaniline, and 4-nitroaniline compounds using the UV-Vis spectrum. To reduce 4-nitrophenol using κC-g-MBA/MNPs/Cu and ιC-g-MBA/MNPs/Cu, the rate constants (Kapp) obtained were 0.37 and 0.25 min-1, and the activity factors (k') were 134 and 193 s-1 g-1, respectively. The catalysts had a good performance in reducing the nitrophenol compounds and due to the magnetic properties of the catalysts, they could easily be separated and used multiple times.

Green cross-linked bionanocomposite of magnetic layered double hydroxide/guar gum polymer as an efficient adsorbent of Cr(VI) from aqueous solution.

A novel bio-adsorbent based on guar gum (GG) was synthesized through the cross-linked polymerization of N,N'-methylene bis-acrylamide (MBA) onto Fe3O4@ nickel aluminum layered double hydroxide (Ni/Al LDH) @ GG bionanocomposite (BNC) using an in situ growth method. The structural, thermal, and morphological properties of the MLG BNC were studied by different techniques. According to field emission scanning electron microscopy, and transmission electron microscopy, there is a uniform distribution of nanoparticles with a particle size of 40-50 nm in the nanocomposite. MLG BNC was used as Cr (VI) adsorbent, and the effect of pH, concentration, and contact time on adsorption capacity was determined. It was observed that the maximum Cr(VI) adsorption by MLG was 101 mg g-1 (pH 6, 30 min). The adsorption isotherm was represented the single-layer, and homogeneous adsorption and the high value of R2 illustrates a good agreement with Langmuir. The adsorption kinetic was the second-order pseudo-model.