Targeting Colorectal Cancer Cells with a Functionalised Calix[4]arene Receptor: Biophysical Studies

Colorectal cancer (CRC) is a disease which is causing a high degree of mortality around the world. The present study reports the antiproliferative impact of the thioacetamide calix[4]arene, CAII receptor on a highly differentiated Caco-2 cell line. This statement is corroborated by the MTT assay results which revealed a reduction in the cell viability with an IC50 value of 19.02 ± 0.04 µM. Microscopic results indicated that at the starting amount of 10 µM of CAII, a decrease in cells confluency can already be observed in addition to changes in cells morphology. Cell metabolic pathway changes were also investigated. 1H NMR findings showed downregulation in lactate, pyruvate, phosphocholine, lipids, and hydroxybutyrate with the upregulation of succinate, indicating a decline in the cells proliferation. Some biochemical alterations in the cells as a result of the CAII treatment were found by Raman spectroscopy.

Computational Modeling Intervertebral Disc Pathophysiology: A Review

Lower back pain is a medical condition of epidemic proportion, and the degeneration of the intervertebral disc has been identified as a major contributor. The etiology of intervertebral disc (IVD) degeneration is multifactorial, depending on age, cell-mediated molecular degradation processes and genetics, which is accelerated by traumatic or gradual mechanical factors. The complexity of such intertwined biochemical and mechanical processes leading to degeneration makes it difficult to quantitatively identify cause–effect relationships through experiments. Computational modeling of the IVD is a powerful investigative tool since it offers the opportunity to vary, observe and isolate the effects of a wide range of phenomena involved in the degenerative process of discs. This review aims at discussing the main findings of finite element models of IVD pathophysiology with a special focus on the different factors contributing to physical changes typical of degenerative phenomena. Models presented are subdivided into those addressing role of nutritional supply, progressive biochemical alterations stemming from an imbalance between anabolic and catabolic processes, aging and those considering mechanical factors as the primary source that induces morphological change within the disc. Limitations of the current models, as well as opportunities for future computational modeling work are also discussed.

768-km Multi-Stage Ultra-Trail Case Study-Muscle Damage, Biochemical Alterations and Strength Loss on Lower Limbs

A series of case studies aimed to evaluate muscular fatigue in running a 768-km ultra-trail race in 11 days. Four non-professional athletes (four males) were enrolled. Muscle damage blood biomarkers (creatine kinase (CK), lactodeshydrogenase (LDH), aspartate transaminase (AST) and alanine aminotransferase (ALT) and lower limb strength were evaluated by using Bosco jumps test; squat jump (SJ), countermovement jump (CMJ) and Abalakov jump (ABA) were assessed before (pre), after the race (post) and for two and nine days during the recovery period (rec2 and rec9), respectively. Results showed: pre-post SJ = −28%, CMJ = −36% and ABA = −21%. Values returned to basal during rec9: SJ = −1%, CMJ = −2% or even exceeded pre-values ABA = +3%. On the contrary, muscle damage blood biomarkers values increased at post; CK = +888%, LDH = +172%, AST = +167% and ALT = +159% and the values returned gradually to baseline at rec9 except for AST = +226% and ALT = +103% which remained higher. Nonparametric bivariate Spearman’s test showed strong correlations (Rs ≥ 0.8) between some jumps and muscle damage biomarkers at post (SJ-LDH Rs = 0.80, SJ-AST Rs = 0.8, ABA-LD H Rs = 0.80 and ABA-AST Rs = 0.80), at rec2 (SJ-CK Rs = 0.80 and SJ-ALT Rs = 0.80) and even during rec9 (ABA-CK). Similarly, some parameters such as accumulated elevation and training volume showed a strong correlation with LDH values after finishing the ultra-trail race. The alteration induced by completing an ultra-trail event in the muscle affects lower limb strength and may in some circumstances result in serious medical conditions including post- exertional rhabdomyolysis.

Association of Acute Postoperative Pain and Cigarette Smoking With Cerebrospinal Fluid Levels of Beta-Endorphin and Substance P

Objectives: Cigarette smoking is associated with postoperative pain perception, which might be mediated by beta-endorphin and substance P. These effects on postoperative pain perception have never been investigated in human cerebrospinal fluid (CSF), which reflects biochemical alterations in the brain. Therefore, we investigated the associations among cigarette smoking, postoperative pain, and levels of beta-endorphin and substance P in human CSF.Methods: We recruited 160 Chinese men (80 active smokers and 80 nonsmokers) who underwent lumbar puncture before anterior cruciate ligament reconstruction, and 5-ml CSF samples were collected. Pain visual analog scale (VAS) scores, post-anesthetic recovery duration (PARD), and smoking variables were obtained. CSF levels of beta-endorphin and substance P were measured.Results: Compared to non-smokers, active smokers had significantly higher pain VAS (2.40 ± 0.67 vs. 1.70 ± 0.86, p < 0.001) and PARD scores (9.13 ± 2.11 vs. 7.27 ± 1.35, p = 0.001), lower CSF beta-endorphin (33.76 ± 1.77 vs. 35.66 ± 2.20, p = 0.001) and higher CSF substance P (2,124.46 ± 217.34 vs. 1,817.65 ± 302.14, p < 0.001) levels. Pain VAS scores correlated with PARD in active smokers (r = 0.443, p = 0.001).Conclusions: Cigarette smoking is associated with increased postoperative pain intensity, shown by delayed pain perception, higher pain VAS scores, and lower beta-endorphin and higher substance P levels in the CSF of active smokers. The more extended postoperative pain perception is delayed, the more pain intensity increases.

Metabolic Profile Characterization of Different Thyroid Nodules Using FTIR Spectroscopy: A Review

Thyroid cancer’s incidence has increased in the last decades, and its diagnosis can be a challenge. Further and complementary testing based in biochemical alterations may be important to correctly identify thyroid cancer and prevent unnecessary surgery. Fourier-transform infrared (FTIR) spectroscopy is a metabolomic technique that has already shown promising results in cancer metabolome analysis of neoplastic thyroid tissue, in the identification and classification of prostate tumor tissues and of breast carcinoma, among others. This work aims to gather and discuss published information on the ability of FTIR spectroscopy to be used in metabolomic studies of the thyroid, including discriminating between benign and malignant thyroid samples and grading and classifying different types of thyroid tumors.

Quercetin Modulates Behavioural and Biochemical Alterations in Stressed Mice

Disruption of the active phase of sleep alters the physiological homeostasis of the body and results in oxidative breakdown which may trigger a wide array of defects. The central nervous system and the metabolic system are some of the most affected systems as described in several literatures. Some plant based compounds with antioxidant property have been previously described in the abrogation of the deleterious effects of active sleep disruption. One of such compounds is quercetin. This study was premeditated to expatiate on the probable neuroprotective effect of quercetin on mice exposed to 72hr active sleep disruption. Mice were allotted into five treatment groups (n = 6): group 1 served as control, group 2 received 10 mL/kg vehicle, groups 3 and 4 received 25 and 50 mg/kg quercetin respectively, and group 5 received 50 mg/kg astaxanthin. Treatment lasted for 7 days while groups 2-5 were exposed to the sleep deprivation protocol starting from day 4. Behavioural tests followed by biochemical assays and histopathological changes in the prefrontal cortex were evaluated. Data were analysed by ANOVA set at p<0.05 significance. The results revealed that quercetin, in both doses, significantly amplified memory performance, attenuated depression-like behaviour, replenished catalase and superoxide dismutase, attenuated nitric oxide levels in brain and liver of mice when compared to control group and protected against loss of prefrontal cortex neurons. In conclusion, quercetin possesses protective effects against sleep deprivation-induced brain damage.

KIM-1 and GADDI-153 gene expression in paracetamol-induced acute kidney injury: effects of N-acetylcysteine, N-acetylmethionine, and N-acetylglucosamine

Objectives Acute kidney injury (AKI) is a critical clinical event characterized by a reduction in the excretory function of the kidneys. N-acetylcysteine (NAC), N-acetylmethionine (NAM) and N-acetylglucosamine (NAG) are antioxidants with scanty known genetic mechanisms. We aimed to assess both kidney injury molecule-1 (KIM-1) and growth-arrested DNA damage-inducible gene-153 (GADD-153) genes expression in paracetamol (PA) induced AKI. Also, to recognize whether NAC, NAM and/or NAG have roles in altering the expression of these genes for ameliorating the AKI induced by PA. Methods The present preliminary study achieved the AKI model by oral administration of PA therapeutic dose for 15 days in experimental male rats. Serum urea, creatinine, and renal oxidative stress parameters were analyzed. Genetic expression of KIM-1 and GADD-153 were determined using real time-PCR. Results Significant elevations of serum urea, creatinine and nitric oxide in renal tissue after PA administration; however, total thiol content was reduced. In addition, both KIM-1 and GADD-153 were upregulated. These biochemical alterations were improved after using NAC and partially after NAM; however, NAG had little effect. Conclusions Up-regulation of both KIM-1 and GADD-153 occur in AKI induced by PA, which was significantly reversed by NAC.

Alterations in Various Biochemical Parameters Among Covid-19 Patients: An Observational Retrospective Analysis

Novel coronavirus causing the pandemic infectious disease termed as COVID-19 is characterized by respiratory illness which may lead on to acute respiratory distress syndrome. Ferritin is a key mediator of immune dysregulation leading on to cytokine storm. Alterations in various biochemical parameters have been widely reported in COVID-19. Early identification of effective biomarkers to assess the severity of this disease is essential. Our study was aimed to evaluate the variations in the routinely analysed biochemical parameters and their association with ferritin levels among COVID patients. The study participants consisted of 270 members among which 149 were COVID positive and 121 were negative. Analysis of the routine biochemical parameters as well as ferritin level were carried out. Among the 149 positive cases, 84 (56.4%) were mild positive with ferritin levels <500ng/ml and 65 (43.6%) were severe positive with ferritin levels >500ng/ml. We reported significant increase in serum ferritin levels in severe positive samples (1449.84 ± 249.47) compared to mild positive samples (230.04 ± 17.41). We observed increased levels of total bilirubin in 12.7%, direct bilirubin in 16.8%, indirect bilirubin in 8.7%, AST in 65.8%, ALT in 44.3%, ALP in 9.4%, GGT in 51.7%, urea in 18.4%, creatinine in 14.3%, BUN in 18.4% and decreased levels of total protein and albumin in 23.5% positive patients compared to negative patients. Ferritin and its associated biochemical parameters act as predictors of COVID severity. These biochemical alterations suggest the significance of early risk assessment and monitoring of COVID patients.

Fucoidan Protects against Acute Sulfoxaflor-Induced Hematological/Biochemical Alterations and Oxidative Stress in Male Mice

Fucoidan is a sulfated polysaccharide which can be found among a number of macroalgea species. It has a broad spectrum of biological activities including anti-oxidant, anti-tumor, immunoregulation, anti-viral and anti-coagulant. The current study was performed to investigate possible protective effects of fucoidan for sulfoxaflor-induced hematological/biochemical alterations and oxidative stress in the blood of male Swiss albino mice. For this purpose, sulfoxaflor was administered at a dose of 15 mg/kg/day (1/50 oral LD50), and fucoidan was administered at a dose of 50 mg/kg/day by oral gavage alone and combined for 24 h and 7 days. Hematological parameters (RBC, HGB, HCT, MCV, MCH, MCHC, Plt, WBC, Neu, Lym and Mon), serum biochemical parameters (AST, ALT, GGT, LDH, BUN, Cre and TBil), and serum oxidative stress/antioxidant markers (8-OHdG, MDA, POC and GSH) were analyzed. The results indicated that sulfoxaflor altered hematological and biochemical parameters and caused oxidative stress in mice; fucoidan ameliorated some hematological and biochemical parameters and exhibited a protective role as an antioxidant against sulfoxaflor-induced oxidative stress.