Cristian Tudor Cozma

Background/Objectives: Despite significant progress, cardiovascular disease remains the primary global cause of disability-adjusted life years. Atherosclerosis, an early form of vascular disorder, is driven by low-grade chronic inflammation and lipid accumulation. Obesity exacerbates atherosclerosis through insulin resistance, adipokine imbalance, and sustained inflammation, leading to endothelial dysfunction. Given this intricate involve-ment, understanding the effect of weight loss on derived indices associated with athero-sclerosis progression is crucial for developing effective strategies against this pervasive health challenge. Methods: 73 overweight or obese adults completed a six-month die-tary-based weight loss intervention. A 15% caloric deficit target was set, excluding poten-tially influencing pharmacotherapy, and limiting physical activity to daily walking. Sta-tistical analysis focused on anthropometric measures, lipid panel parameters and derived atherosclerosis indices, the latter stratified by gender and weight drop magnitude to as-sess robustness. Results: The intervention returned a median weight loss of 11.8 (IQR: 8 – 19) kg. Before-After analysis showed statistically significant improvement in anthropo-metric indices and most lipid profile components. Castelli Risk Index (CRI)-2 significantly improved (p < 0.05) from 3.28 (IQR: 2.57 – 4) to 3.22 (IQR: 2.55 – 3.71), Lipid Accumulation Product (LAP) decreased from 62.6 to 40.3 (p< 0.001). To assess the effect of weight loss on the atherogenic profile of patients, we proposed an atherogenic load index (Atherogenic Central Load Index (ACLI)). ACLI decreased significantly following the hypocaloric diet and showed a significant correlation with the inflammatory markers hs-CRP and IL-6. ACLI showed a strong, inversely significant correlation (p < 0.05) with AIP, hs-CRP and IL-6, at the time of intervention initiation and after 6 months. The evaluation of the ob-tained AUC values allowed to clearly highlight the superior discrimination performance of ACLI regarding the inflammatory markers hs-CRP and IL-6 in obese or overweight pa-tients involved in dietary interventions for weight loss. The AUC values for ACLI were significantly higher than those corresponding to the other atherogenic indices evaluated (AIP, CRI-1 and CRI-2) for both evaluation times (before intervention and after interven-tion. Conclusions. This study demonstrates that a calculated dietary deficit alone is suffi-cient to significantly improve critical surrogate markers of atherosclerosis and visceral adiposity, specifically AIP, CRI-2, LAP and the proposed central atherogenic load index (ACLI). Our results highlighted the superior potential of the ACLI index for predicting en-dothelial dysfunction with reference to the inflammatory markers hs-CRP and IL-6, com-pared to traditional derived indices associated with atherosclerosis progression (AIP, CRI-1 and CRI-2). These findings suggest physically demanding exercise regimens are not mandatory to mitigate CVD risk. Dietary-focused interventions offer an effective strategy for improving cardiovascular health in selected obese populations without requiring in-tensive physical training.

Objective: Uncovering the renoprotective and anti-inflammatory effects of atorvastatin treatment in diabetic-and-obese rats by employing traditional renal function indicators (urea and creatinine) and four prototypical cytokines (IL-1β, il-6, IL-17α, TNFα). Method: Twenty-eight male Wistar rats, aged 6 months, 350–400 g, were randomized into four groups. The first group, G-I, the denominated control, were fed standard chow over the whole course of the experiments. The rodents in G-II were exposed to a High-Fat Diet. The last two groups were exposed to Streptozotocin peritoneal injection (35 mg/kg of body weight). A short biochemical assessment was performed before diabetes model induction to ensure appropriate glucose metabolism before experiments. Following model induction, only rodents in group G-IV were gradually introduced to the same High-Fat Diet as received by G-II. Model confirmation 10 days after injections marked the start of statin treatment in group G-IV, by daily gavage of atorvastatin 20 mg/kg of body weight/day for 21 days. At the end of the experiments, the biochemical profile of interest comprised typical renal retention byproducts (urea and creatinine) and the inflammatory profile described using plasma levels of TNFα, IL-17α, IL-6, and IL-1β. Results: Treatment with Atorvastatin was associated with a statistically significant improvement in renal function in G-IV compared to untreated diabetic rodents in G-III. Changes in inflammatory activity showed partial association with statin therapy, TNFα and IL-17α mirroring the trend in urea and creatinine values. Conclusions: Our results indicate that atorvastatin treatment yields a myriad of pleiotropic activities, among which renal protection was clearly demonstrated in this model of diabetic-and-obese rodents. The statin impact on inflammation regulation may not be as clear-cut, but the potential synergy of renal function preservation and partial tapering of inflammatory activity requires further research in severely metabolically challenged models.

Objective: In our experimental study, we evaluated the influence of treatment with atorvastatin on the antioxidant activity of intracellular and extracellular systems factors, homocysteine levels (Hcy), and lipid profiles in obese and diabetic rats. Method: Twenty-one male Wistar rats, aged 6 months, 450–550 g, were allocated into three groups. From the beginning of the study, the first group (G-I, control) received only standard food, while the second and third groups (G II—obese, G III—diabetic) were administered a high-fat diet (HFD) with 2% cholesterol. After 2 weeks of accommodation, the specimens in G-III were injected intraperitoneal (i.p.) streptozotocin (35 mg of body weight, pH 4.5), intervention followed by the onset of type 2 diabetes mellitus. Following confirmation of diabetes onset, the specimens in G III were administered concomitantly with the HFD a daily gavage of atorvastatin 20 mg of body weight/day for 20 days. We measured, at the beginning and the end of the study, the Hcy levels, lipid profile, vitamin B12, B6, folic acid, and various parameters of oxidative stress (OS)—total antioxidant status (TAS), glutathione peroxidase (GPX) and superoxide dismutase (SOD). Results: After treatment with atorvastatin, the lipid profile in G III significantly improved compared to the other two groups, but enzymatic markers of oxidative stress did not closely parallel this trend. However, after the treatment of statin, we observed an important reduction in Hcy values. Conclusion: Our results demonstrate that treatment with atorvastatin can be used not only for its lipid-lowering properties and antioxidant effects but also to reduce Hcy concentration in this experimental model of diabetic rats. Moreover, atorvastatin therapy improves lipid profiles, reduces inflammation, suppresses oxidation, and decreases Hcy levels, potentially preventing major adverse cardiovascular events.

Chronic kidney disease (CKD) stands as a prominent non-communicable ailment, significantly impacting life expectancy. Physiopathology stands mainly upon the triangle represented by parathormone–Vitamin D–Fibroblast Growth Factor-23. Parathormone (PTH), the key hormone in mineral homeostasis, is one of the less easily modifiable parameters in CKD; however, it stands as a significant marker for assessing the risk of complications. The updated “trade-off hypothesis” reveals that levels of PTH spike out of the normal range as early as stage G2 CKD, advancing it as a possible determinant of systemic damage. The present review aims to review the effects exhibited by PTH on several organs while linking the molecular mechanisms to the observed actions in the context of CKD. From a diagnostic perspective, PTH is the most reliable and accessible biochemical marker in CKD, but its trend bears a higher significance on a patient’s prognosis rather than the absolute value. Classically, PTH acts in a dichotomous manner on bone tissue, maintaining a balance between formation and resorption. Under the uremic conditions of advanced CKD, the altered intestinal microbiota majorly tips the balance towards bone lysis. Probiotic treatment has proven reliable in animal models, but in humans, data are limited. Regarding bone status, persistently high levels of PTH determine a reduction in mineral density and a concurrent increase in fracture risk. Pharmacological manipulation of serum PTH requires appropriate patient selection and monitoring since dangerously low levels of PTH may completely inhibit bone turnover. Moreover, the altered mineral balance extends to the cardiovascular system, promoting vascular calcifications. Lastly, the involvement of PTH in the Renin–Angiotensin–Aldosterone axis highlights the importance of opting for the appropriate pharmacological agent should hypertension develop.

The COVID-19 pandemic has put a tremendous stress on the medical community over the last two years. Managing the infection proved a lot more difficult after several research communities started to recognize the long-term effects of this disease. The cellular receptor for the virus was identified as angiotensin-converting enzyme-2 (ACE2), a molecule responsible for a wide array of processes, broadly variable amongst different organs. Angiotensin (Ang) 1-7 is the product of Ang II, a decaying reaction catalysed by ACE2. The effects observed after altering the level of ACE2 are essentially related to the variation of Ang 1-7. The renin-angiotensin-aldosterone system (RAAS) is comprised of two main branches, with ACE2 representing a crucial component of the protective part of the complex. The ACE2/Ang (1-7) axis is well represented in the testis, heart, brain, kidney, and intestine. Infection with the novel SARS-CoV-2 virus determines downregulation of ACE2 and interrupts the equilibrium between ACE and ACE2 in these organs. In this review, we highlight the link between the local effects of RAAS and the consequences of COVID-19 infection as they arise from observational studies.