In recent years, one of the most important issues in public health is the rapid growth of antibiotic resistance among pathogens. Multidrug-resistant (MDR) strains (mainly Enterobacteriaceae and non-fermenting bacilli) cause severe infections, against which commonly used pharmaceuticals are ineffective. Therefore, there is an urgent need for new treatment options and drugs with innovative mechanisms of action. Natural compounds, especially alkaloids, are showing promising potential in this area. This review focuses on the ability of the isoquinoline alkaloid berberine (BRB) to overcome various resistance mechanisms against conventional antimicrobial agents. BRB has demonstrated significant activity in inhibiting efflux pumps of the RND (Resistance-Nodulation-Cell Division) family, such as MexAB-OprM (P. aeruginosa) and AdeABC (A. baumannii). Moreover, BRB was able to decrease quorum sensing activity in both Gram-positive and Gram-negative pathogens, resulting in reduced biofilm formation and lower bacterial virulence. Additionally, BRB has been identified as a potential inhibitor of FtsZ, a key protein responsible for bacterial cell division. Particularly noteworthy, though requiring further investigation, are reports suggesting that BRB might inhibit β-lactamase enzymes, including NDM, AmpC, and ESβL types. The pleiotropic antibacterial actions of BRB, distinct from the mechanisms of traditional antibiotics, offer hope for breaking bacterial resistance. However, more extensive studies, especially in vivo, are necessary to fully evaluate the clinical potential of BRB and determine its practical applicability in combating antibiotic-resistant infections.
Skin cancers are associated with a significant psychological burden across all age groups, particularly as their global incidence continues to rise. Ultraviolet (UV) radiation—primarily UVA and UVB—remains the leading etiological factor, inducing DNA mutations in key genes such as TP53 and BRAF. Among skin cancers, basal cell carcinoma (BCC) is the most prevalent and typically indolent. In contrast, squamous cell carcinoma (SCC) tends to be more invasive, while melanoma is the most aggressive and prone to metastasis. Melanoma is especially concerning due to its rapid dissemination and its occurrence not only on the skin but also in ocular, mucosal, and nail tissues. These challenges, along with rising treatment resistance and mortality, underscore the urgent need for novel anticancer agents. Berberine—a plant-derived isoquinoline alkaloid—has attracted increasing attention for its broad-spectrum anticancer potential, including against skin cancers. In this review, we summarize current evidence regarding berberine’s mechanisms of action in melanoma and SCC, emphasizing both its preventive and therapeutic effects. We further explore its potential as an adjuvant agent in combination with conventional treatments, offering a promising avenue for enhancing the clinical outcomes of skin cancer therapy.
In an era of increasing antibiotic resistance among pathogens, the treatment options for infectious diseases are diminishing. One of the clinical groups especially vulnerable to this threat are patients who are hospitalized in intensive care units due to ventilator-associated pneumonia caused by multidrug-resistant/extensively drug-resistant Gram-negative bacteria. In order to prevent the exhaustion of therapeutic options for this life-threatening condition, there is an urgent need for new pharmaceuticals. Novel β-lactam antibiotics, including combinations of cephalosporins with β-lactamase inhibitors, are proposed as a solution to this escalating problem. The unique mechanism of action, distinctive to this new group of siderophore cephalosporins, can overcome multidrug resistance, which is raising high expectations. In this review, we present the summarized results of clinical trials, in vitro studies, and case studies on the therapeutic efficacy of cefoperazone-sulbactam, ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol in the treatment of ventilator-associated pneumonia. We demonstrate that treatment strategies based on siderophore cephalosporins and combinations of β-lactams with β-lactamases inhibitors show comparable or higher clinical efficacy than those used with classic pharmaceuticals, like carbapenems, colistin, or tigecycline, and are often associated with a lower risk of adverse events.
Renal cell carcinoma is a common disease, and clear cell renal cell carcinoma is the most common histological type. Renal cell carcinoma has a tendency to infiltrate the venous system including the inferior vena cava and the right atrium of the heart. We present the cases of two patients with renal cell carcinoma with stage IV tumor thrombus according to the Mayo classification, who underwent surgery under transesophageal echocardiography guidance. Apart from standard imaging methods used in renal cancer with tumor thrombus reaching the right atrium of the heart, we consider transesophageal echocardiography to be a very useful tool in the diagnostic work-up, patient monitoring, and selection of appropriate surgical technique.
8 July 2025 in Journal of Education, Health and Sport
Introduction and purpose:Sleep deprivation (SD), paradoxically, has been shown to induce rapid antidepressant effects in patients with depressive disorders. This review explores the neurobiological underpinnings, clinical efficacy, and therapeutic strategies involving SD, aiming to clarify the mechanisms responsible for its mood-elevating effects and to assess its role in modern treatment of depression. Description of the state of knowledge:Clinical evidence consistently shows that a single night of total or partial SD can lead to a rapid reduction in depressive symptoms in approximately 40–60% of patients. However, these effects are short-lived, with relapse typically occurring after recovery sleep. Combination therapies, such as SD with phase advance and bright light exposure, have been developed to prolong therapeutic benefits. On the neurobiological level, SD appears to act through multiple pathways: resetting dysregulated circadian rhythms, enhancing monoaminergic neurotransmission (particularly serotonin and dopamine), upregulating brain-derived neurotrophic factor (BDNF), and inducing synaptic plasticity. Acute activation of the hypothalamic–pituitary–adrenal axis and transient increases in inflammatory markers have also been observed, suggesting a complex physiological adaptation that accompanies mood improvement. Additionally, glial mechanisms involving adenosine signaling may contribute to the antidepressant response. Summary:Sleep deprivation represents a unique, non-pharmacological intervention capable of rapidly alleviating depressive symptoms. Although transient on its own, its combination with chronotherapeutic or pharmacological strategies offers promising avenues for sustained therapeutic effect. Insights from SD research deepen our understanding of depression’s neurobiology and support the development of fast-acting antidepressant treatments that target circadian and neuroplastic mechanisms.