Nicoleta Mirela Blebea

Background/Objectives: Mental and neurological disorders contribute substantially to the global burden of disease, affecting people of all ages and backgrounds. As their prevalence increases with age, their overall impact is expected to grow in the coming decades. Although psychological and pharmacological treatments are available, many patients fail to achieve satisfactory outcomes, underscoring the need for improved therapeutic strategies. Cannabis sativa L. has been used for medicinal purposes for centuries, and cannabidiol (CBD) has attracted increasing attention because of its broad therapeutic potential. Scientific studies indicate that CBD may be beneficial in several mental and neurological disorders. Methods: A comprehensive literature search was conducted to identify articles investigating the therapeutic potential of CBD and cannabis in selected disorders. Results: Evidence from preclinical and clinical studies, together with findings from the broader cannabis literature, indicates that CBD may offer therapeutic benefits in a range of conditions, including Alzheimer’s and Parkinson’s disease, anxiety disorders, and epilepsy. Emerging data also support its potential use as an adjunctive therapy for COVID-19. Current research has improved understanding of the neurobiological mechanisms underlying these disorders and the molecular pathways through which CBD may exert its effects. CBD has demonstrated good tolerability, with predominantly mild adverse effects and a favorable safety profile. Conclusions: Despite promising findings, many available studies are preclinical or involve small patient cohorts, and the mechanisms underlying the therapeutic effects of CBD remain incompletely understood. Further well-designed, randomized, controlled, multicenter trials are needed to establish the efficacy and safety of CBD and support its integration into clinical practice.

Solid-state fermentation (SSF) is a long-established biotechnological approach gaining renewed interest for its ability to enhance nutrient availability and improve the functional properties of agro-industrial by-products. This strategy is particularly relevant for early post-weaning piglets, which are highly susceptible to weaning stress due to an immature digestive system and a gut microbiota not yet adapted to solid feed. In this study, the fermentation parameters of flaxseed cake were optimized using a Plackett–Burman experimental design. Protease activity was selected as the response variable due to its relevance for improving protein degradation and potential digestibility in fermented feed ingredients. Accordingly, based on the statistical analysis, the conditions selected for the in vivo trial were 1% molasses, 0.5% yeast extract, 0.05% CaCl₂, 0.5% NaCl, 7.5% inoculum (4.12 × 10⁹ CFU/mL), 60% moisture, and 72 h fermentation. Fermentation time was identified as the main factor positively influencing protease production, while higher CaCl₂ concentrations and inoculum levels negatively affected enzyme activity. Optimization increased protease activity, microbial viability and free amino acid content. In addition, SSF reorganizes the carbohydrate profile by reducing structural fiber fractions, with neutral detergent fiber and acid detergent fiber decreasing by 27% and 29%, respectively, while simultaneously increasing soluble carbohydrates by 14.67%. Phytic acid content being also reduced by 23.81%. A pilot nutritional trial on post-weaned piglets (35 days old) showed that including 8% fermented flaxseed cakes (FFSC group) improved body weight, average daily gain, feed conversion ratio, and diarrhea score, without affecting average daily feed intake, compared with 8% unfermented flaxseed cakes (FSC group). These performance improvements were accompanied by changes in fermentation metabolites and gut microbial composition. Lower isovalerate concentrations suggested reduced proteolysis, while higher propionate levels may contribute to increased blood glucose availability in the FFSC group. These changes coincided with a shift in microbial composition, characterized by a reduced abundance of methanogenic archaea and increased abundances of taxa such as Lactobacillus, Enterococcus, and members of the Lachnospiraceae and Eubacteriaceae families.

Background/Objectives: In the broad and current context of antimicrobial resistance, antibiotic management and therapeutic surveillance are essential in hospitals. The present study (five-year retrospective, 2020–2024) aimed to analyze antibiotic consumption in relation to pathogens identified in a multidisciplinary hospital. Results: In terms of antibiotic consumption (overall 2020–2024), although initially Watch antibiotics were predominantly used, a decrease was observed in favor of Access class antibiotics (sharply increase from 2022 to 2023 and maximum in 2024). For Reserve antibiotics, only slight annual fluctuations were observed, but there was an important reduction in colistin consumption. The most used were cephalosporins (cefazolin, cefuroxime and ceftriaxone), carbapenems (meropenem and ertapenem), vancomycin and linezolid. Regarding pathogens, the most notable were: Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Enterococcus spp., Pseudomonas aeruginosa. Among the ESKAPE bacteria, Acinetobacter baumannii was the least frequent in our samples. ESKAPE bacteria predominantly colonized specimens from the respiratory tract, digestive tract, skin and soft tissue. Resistant strains were observed, mainly Methicillin-resistant Staphylococcus aureus (MRSA) and Extended-Spectrum Beta-Lactamase (ESBL) Klebsiella spp., but no alarming increases in number were recorded in the analyzed period. Methods: The analysis was carried out using tools recommended by the World Health Organisation (Access Watch Reserve antibiotics classification (AWaRe); Bacterial Priority Pathogen List (BBPL); Defined Daily Dose (DDD)), Average Annual Percent Change (AAPC) calculation and ESKAPE classification (bacteria group: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.). Conclusions: Relatively stable trends in bacterial isolates and resistant strains over five years (2020–2024) are consistent with effective antimicrobial stewardship practices.

Diabetic neuropathy (DN) is one of the most prevalent complications of diabetes mellitus, affecting a substantial proportion of patients and contributing to progressive sensorimotor dysfunction. Despite its clinical significance, available treatments are often insufficient and associated with undesirable effects. This study aims to evaluate the potential of Morus alba (MA), Angelica archangelica (AA), Valeriana officinalis (VO), and Passiflora incarnata (PI) extracts in ameliorating nociceptive alterations and inflammatory markers in the alloxan-induced diabetic rat model. Male Wistar rats with alloxan-induced DN received oral administration of the plant extracts (200 mg/kg/day) or gabapentin (100 mg/kg/day) for 15 days, the dosage regimen being established based on prior efficacy data in preclinical neuropathy models. Behavioral assessments of thermal and mechanical hypersensitivity were conducted using hot plate, tail withdrawal, von Frey, and Randall–Sellito tests. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were quantified in brain and liver homogenates to evaluate neuro-inflammatory responses. All plant extracts produced significant improvements in nociceptive thresholds compared to diabetic control, with the most marked effects observed for MA extract. Pro-inflammatory cytokine levels were significantly reduced in all treatment groups, with MA and AA extracts inducing the most significant reductions in TNF-α and IL-6 concentrations. Computational target prediction and molecular docking analyses revealed that key phytochemicals from the plant extracts may exert antihyperalgesic effects through multi-target modulation, notably via interactions with AAK1, a kinase involved in neuropathic pain signaling. The investigated plant extracts displayed significant antihyperalgesic and anti-inflammatory activities in a rat model of DN. Among them, MA extract revealed the most consistent therapeutic profile, supporting its potential role as a strategy for managing DN.

The current study evaluated the anticonvulsant properties of ethanolic extracts from Morus alba, Angelica archangelica, Passiflora incarnata, and Valeriana officinalis using integrated phytochemical, in vivo, biochemical, and computational approaches. Phytochemical analysis by UHPLC-HRMS/MS revealed the presence of various bioactive compounds, notably flavonoids such as isorhamnetin, quercetin, and kaempferol. In an electroshock-induced seizure model, Morus alba extract (MAE, 100 mg/kg) demonstrated significant anticonvulsant effects, reducing both seizure duration and incidence, likely mediated by flavonoid interactions with GABA-A and 5-HT3A receptors, as suggested by target prediction and molecular docking analyses. The extracts of Angelica archangelica (AAE, 100 mg/kg) and Passiflora incarnata (PIE, 50 mg/kg) exhibited moderate, non-significant anticonvulsant activities. At the same time, Valeriana officinalis (VOE, 50 mg/kg) displayed considerable antioxidant and anti-inflammatory properties but limited seizure protection. All extracts significantly reduced brain inflammation markers (TNF-α) and enhanced antioxidant defenses, as indicated by total thiols. Molecular docking further supported the interaction of key phytochemicals, including naringenin and chlorogenic acid, with human and mouse 5-HT3A receptors. Overall, Morus alba extract exhibited promising therapeutic potential for epilepsy management, warranting further investigation into chronic seizure models and optimized dosing strategies.

The endocannabinoid system (ECS) is a vital biological network essential for maintaining homeostasis and supporting various physiological functions. It comprises cannabinoid receptors, endogenous lipid-based ligands, known as endocannabinoids, as well as metabolic enzymes and associated proteins responsible for regulating their levels within tissues. The ECS plays a central role in modulating processes involving the central nervous system (CNS). Recent studies have highlighted its antioxidant, anti-inflammatory, and neuroprotective properties. The therapeutic potential of cannabinoids, particularly phytocannabinoids derived from plants, has attracted significant attention in medical and pharmaceutical research. This interest has grown in parallel with the increasing availability of cannabinoid-based food supplements on the pharmaceutical market. Given the complexity of the ECS and its broad range of interactions, the discovery of this system has spurred extensive investigations into the use of cannabinoids for various health conditions. In this review, we examine recent preclinical evidence supporting the use of phytocannabinoids in the context of neurodegenerative diseases, particularly in Alzheimer’s disease and Parkinson’s disease. Targeting the ECS through phytocannabinoid-based pharmacological modulation offers a promising therapeutic strategy for these neurological disorders. Among these compounds, cannabidiol has emerged as a key focus of research due to its multifaceted effects and favorable safety profile. Nonetheless, continued investigation is necessary to clarify its mechanisms of action, and to develop effective, evidence-based clinical applications.

Diuretics are a class of pharmacological agents that promote the renal excretion of water and electrolytes, increasing urine output and reducing fluid retention. They play a critical role in the management of edematous syndromes, irrespective of their etiology (cardiac, renal, or hepatic), as well as in the treatment of hypertension (HTA). The mechanism of action of diuretics can be classified as either renal, as seen with saluretic diuretics that inhibit sodium and water reabsorption at various segments of the nephron, or extrarenal, involving alterations in the glomerular filtration pressure or osmotic mechanisms. Based on their site of action and mechanism, diuretics are categorized into multiple classes, including loop diuretics, thiazide and thiazide-like diuretics, potassium-sparing diuretics, carbonic anhydrase inhibitors, and osmotic diuretics. These agents are frequently used in combination with other antihypertensive or heart failure medications to optimize therapeutic efficacy. By reducing the blood volume and peripheral vascular resistance, diuretics improve cardiac function, lower blood pressure, and enhance exercise tolerance. Additionally, they are employed in managing chronic kidney disease (CKD), electrolyte imbalances, and specific metabolic disorders. Given the potential for adverse effects such as electrolyte disturbances and renal dysfunction, diuretic therapy should be individualized, with the careful monitoring of the dosage, patient response, and comorbid conditions. Patient education on adherence, lifestyle modifications, and the recognition of side effects is essential for optimizing the therapeutic outcomes and minimizing the risks associated with diuretic therapy.

Chitosan (CS), a versatile biopolymer obtained through the deacetylation of chitin, has gained significant interest in biomedical and pharmaceutical applications due to its biocompatibility, biodegradability, and unique gel-forming capabilities. This review comprehensively analyzes CS-based gel development, covering its extraction from various natural sources, gelation mechanisms, and biomedical applications. Different extraction methods, including chemical, biological, and green techniques, are discussed regarding efficiency and sustainability. The review explores the physicochemical properties of CS that influence its gelation behavior, highlighting various gelation mechanisms such as physical, ionic, and chemical cross-linking. Recent advances in gel formation, including Schiff base reactions, Diels–Alder click chemistry, and thermosensitive gelation, have expanded the applicability of CS hydrogels. Furthermore, CS-based gels have demonstrated potential in wound healing, tissue engineering, drug delivery, and antimicrobial applications, offering controlled drug release, enhanced biocompatibility, and tunable mechanical properties. The incorporation of nanomaterials, bioactive molecules, and functional cross-linkers has further improved hydrogel performance. The current review underscores the growing significance of CS-based gels as innovative biomaterials in regenerative medicine and pharmaceutical sciences.

Autophagy and mitophagy are critical cellular processes that maintain homeostasis by removing damaged organelles and promoting cellular survival under stress conditions. In the context of diabetic kidney disease, these mechanisms play essential roles in mitigating cellular damage. This review provides an in-depth analysis of the recent literature on the relationship between autophagy, mitophagy, and diabetic kidney disease, highlighting the current state of knowledge, existing research gaps, and potential areas for future investigations. Diabetic nephropathy (DN) is traditionally defined as a specific form of kidney disease caused by long-standing diabetes, characterized by the classic histological lesions in the kidney, including mesangial expansion, glomerular basement membrane thickening, nodular glomerulosclerosis (Kimmelstiel–Wilson nodules), and podocyte injury. Clinical markers for DN are albuminuria and the gradual decline in glomerular filtration rate (GFR). Diabetic kidney disease (DKD) is a broader and more inclusive term, for all forms of chronic kidney disease (CKD) in individuals with diabetes, regardless of the underlying pathology. This includes patients who may have diabetes-associated kidney damage without the typical histological findings of diabetic nephropathy. It also accounts for patients with other coexisting kidney diseases (e.g., hypertensive nephrosclerosis, ischemic nephropathy, tubulointerstitial nephropathies), even in the absence of albuminuria, such as a reduction in GFR.

Neuropathic pain (NeP) is a complex and debilitating condition that impacts millions of people globally. Although various treatment options exist, their effectiveness is often limited, and they can be accompanied by significant side effects. In recent years, there has been increasing interest in targeting the N-methyl-D-aspartate receptor (NMDAR) as a potential therapeutic approach to alleviate different types of neuropathic pain. This narrative review aims to provide a comprehensive examination of NMDAR antagonists, specifically ketamine, memantine, methadone, amantadine, carbamazepine, valproic acid, phenytoin, dextromethorphan, riluzole, and levorphanol, in the management of NeP. By analyzing and summarizing current preclinical and clinical studies, this review seeks to evaluate the efficacy of these pharmacologic agents in providing adequate relief for NeP.