Soluble CD163 (sCD163) is a circulating inflammatory mediator, indicative of acute and chronic, systemic and non-systemic inflammatory conditions. It is the cleavage outcome, consisting of almost the entire extracellular domain, of the CD163, a receptor expressed in monocytic lineages. Its expression is proportional to the abundance of CD163⁺ macrophages. Various mechanisms trigger the shedding of the CD163 receptor or the accumulation of CD163-expressing macrophages, inducing the sCD163 concentration in the circulation and bodily fluids. The activities of sCD163 range from hemoglobin (Hb) scavenging, macrophage marker, decoy receptor for cytokines, participation in immune defense mechanisms, and paracrine effects in various tissues, including the endothelium. It is an established marker of macrophage activation and thus participates in many diseases, including chronic inflammatory conditions, such as atherosclerosis, asthma, and rheumatoid arthritis; acute inflammatory conditions, such as sepsis, hepatitis, and malaria; insulin resistance; diabetes; and tumors. The sCD163 levels have been correlated with the severity, stage of the disease, and clinical outcome for many of these conditions. This review article summarizes the expression and role of sCD163 and its precursor protein, CD163, outlines the sCD163 generation mechanisms, the biological activities, and the known underlying molecular mechanisms, with an emphasis on its impact on the endothelium and its contribution in the pathophysiology of human diseases.

Intranasal administration offers an alternative and promising approach for direct nose-to-brain delivery. Herein, we developed two chitosan (CHT)-coated (and uncoated) nanoformulations of BNN27 (a synthetic C-17-spiro-dehydroepiandrosterone analogue), liposomes (LIPs), and nanoemulsions (NEs), and compared their properties and brain disposition (in vitro and in vivo). LIPs were formulated by thin film hydration and coated with CHT by dropwise addition. BNN27-loaded NEs (BNEs) were developed by spontaneous emulsification and optimized for stability and mucoadhesive properties. Mucoadhesive properties were evaluated by mucin adherence. Negatively charged CHT-coated LIPs (with 0.1% CHT/lipid) demonstrated the highest coating efficiency and mucoadhesion. BNEs containing 10% w/w Capmul-MCM and 0.3% w/w CHT demonstrated the optimal properties. Transport of LIP or NE-associated rhodamine-lipid across the blood–brain barrier (in vitro) was significantly higher for NEs compared to LIPs, and the CHT coating demonstrated a negative effect on transport. However, the CHT-coated BNEs demonstrated higher and faster in vivo brain disposition following intranasal administration compared to CHT-LIPs. For both BNEs and LIPs, CHT-coating resulted in the increased (in vivo) brain disposition of BNN27. Current results prove that CHT-coated NEs consisting of compatible nasal administration ingredients succeeded in to delivering more BNN27 to the brain (and faster) compared to the CHT-coated LIPs.

In this study, liposomes coated with novel multifunctional polymers were proposed as an innovative platform for tumor targeted drug delivery. Novel Folic acid–Cysteine-Thiolated chitosan (FTC) derivatives possessing active targeting ability and redox responsivity were synthesized, characterized, and employed to develop FTC-coated liposomes. Liposomes were characterized for size, surface charge and drug encapsulation efficiency before and after coating. The formation of a coating layer on liposomal surface was confirmed by the slight increase in particle size and by zeta-potential changes. FTC-coated liposomes showed a redox-dependent drug release profile: good stability at physiological conditions and rapid release of liposome-entrapped calcein in presence of glutathione. Moreover, the uptake and cytotoxic activity of doxorubicin-loaded FTC-coated liposomes was evaluated on murine B16-F10 and human SKMEL2 melanoma cancer cells. Results demonstrated enhanced uptake and antitumor efficacy of FTC-coated liposomes compared to control chitosan-coated liposomes in both cancer lines, which is attributed to higher cellular uptake via folate receptor-mediated endocytosis and to triggered drug release by the reductive microenvironment of tumor cells. The proposed novel liposomes show great potential as nanocarriers for targeted therapy of cancer.

Background and purpose: Balance and gait problems pose a significant burden in Parkinson’s disease (PD), and they are often poorly treated with levodopa. We intended to summarize evidence of mid- and long-term impact of various physiotherapeutic interventions (≥3 months post-intervention) on dynamic balance, gait, and general motor function in patients with PD. Method: A systematic search was conducted across the PubMed, Cochrane Library, and Scopus databases to identify controlled clinical trials on sustained effects of various exercise interventions in PD on the outcomes of interest (lasting ≥ 3 months after completion of the exercise program). We conducted meta-analyses on commonly used clinical measures of dynamic balance and gait ability, as well as on UPDRS-III scores using the Comprehensive Meta-Analysis Software (CMA). Results: A total of 26 studies were included in meta-analyses, with a total of 1261 participants in the experimental and 989 participants in the control groups. Positive cumulative effects at the post-exercise follow-up (3 to 23 months) were shown in favor of the intervention group regarding balance (SMD = 0.512, 95% CI [0.240, 0.785], p < 0.001, I² = 87%), gait (SMD = 0.614, 95% CI [0.301, 0.926], p < 0.001, I² = 75%), and general motor function (SMD = 0.922, 95% CI [0.559, 1.285], p < 0.001, I² = 87%). Heterogeneity among studies was high for all three outcomes, apparently reflecting diversity with regard to patient characteristics, type, and duration of intervention, as well as the method of outcome assessment. The certainty of evidence was consequently judged as ‘’low’’ to ‘’moderate,’’ according to the GRADE system. Subgroup analyses revealed that balance can sustainably improve mostly through multimodal rather than targeted balance-oriented exercise but also through dual-task exercise, tai chi, and Pilates. Gait showed improvement at follow-up mainly through multimodal exercise, aerobic exercise, dual-task exercise, and Pilates, with benefits confined to early- and mid-stage disease. Sustained UPDRS-III improvement could be achieved through multimodal exercise, which showed a large overall effect but also through aerobic, resistance, and dual-task training, tai chi and qigong. Conclusions: Exercise interventions can improve balance and gait, as well as preserve the overall motor function in patients with PD, also in the mid- and long-term post-intervention periods.