Inorganic nanoparticle-cored dendrimers for biomedical applications: A review.

Hybrid nanostructures exhibit a synergistic combination of features derived from their individual components, showcasing novel characteristics resulting from their distinctive structure and chemical/physical properties. Surface modifiers play a pivotal role in shaping INPs' primary attributes, influencing their physicochemical properties, stability, and functional applications. Among these modifiers, dendrimers have gained attention as highly effective multifunctional agents for INPs, owing to their unique structural qualities, dendritic effects, and physicochemical properties. Dendrimers can be seamlessly integrated with diverse inorganic nanostructures, including metal NPs, carbon nanostructures, silica NPs, and QDs. Two viable approaches to achieving this integration involve either growing or grafting dendrimers, resulting in inorganic nanostructure-cored dendrimers. The initial step involves functionalizing the nanostructures' surface, followed by the generation of dendrimers through stepwise growth or attachment of pre-synthesized dendrimer branches. This hybridization imparts superior qualities to the resulting structure, including biocompatibility, solubility, high cargo loading capacity, and substantial functionalization potential. Combining the unique properties of dendrimers with those of the inorganic nanostructure cores creates a multifunctional system suitable for diverse applications such as theranostics, bio-sensing, component isolation, chemotherapy, and cargo-carrying applications. This review summarizes the recent developments, with a specific focus on the last five years, within the realm of dendrimers. It delves into their role as modifiers of INPs and explores the potential applications of INP-cored dendrimers in the biomedical applications.

Repurposing of substances with lactone moiety for the treatment of γ-Hydroxybutyric acid and γ-Butyrolactone intoxication through modulating paraoxonase and PPARγ.

GHB and GBL are highly accessible recreational drugs of abuse with a high risk of adverse effects and mortality while no specific antidotes exist. These components can also be found in the clinical setting, beverages, and cosmetic products, leading to unwanted exposures and further intoxications. As the structural analogue of GABA, GHB is suggested as the primary mediator of GHB/GBL effects. We further suggest that GBL might be as critical as GHB in this process, acting through PPARγ as its receptor. Moreover, PPARγ and PON (i.e., the GHB-GBL converting enzyme) can be targeted for GHB/GBL addiction and intoxication, leading to modulation of the GHB-GBL balance and blockage of their effects. We suggest that repurposing substances with lactone moiety such as bacterial lactones, sesquiterpene lactones, and statins might lead to potential therapeutic options as they occupy the active sites of PPARγ and PON and interfere with the GHB-GBL balance. In conclusion, this hypothesis improves the GHB/GBL mechanism of action, suggests potential therapeutic options, and highlights the necessity of classifying GBL as a controlled substance.

Centrally-located transverse myelitis would facilitate the differentiation of NMOSD and MOG-AD from MS.

OBJECTIVES: Differentiating neuromyelitis optica spectrum disorder (NMOSD) and Myelin oligodendrocyte glycoprotein antibody disease (MOG-AD) from multiple sclerosis (MS) is important since MS therapies might result in progression and relapse of the former diseases. Evidence of long extending transverse myelitis (LETM) in magnetic resonance imaging (MRI) is one of the requirements to make an NMOSD diagnosis. However, centrally located lesions on spinal MRI may bring higher sensitivity and specificity to the NMOSD and MOG-AD diagnosis. METHODS: We aimed to assess the association between NMOSD diagnosis and the presence of centrally located lesions at disease onset. We reviewed 102 medical records from the Isfahan MS clinic who presented with cervical cord lesions and 17 MS, 23 NMOSD, and 6 MOG-AD patients were selected. We collected demographic, clinical, and MRI data of patients who had clinical presentations of cervical cord lesion at disease onset, and the characteristics of the lesion were studied. RESULTS: There was an association between NMOSD diagnosis and presence of a centrally located lesion (CLTM) (P < 0.001), presence of an LETM (P < 0.001), and an intermediate to high axial cord expansion (P < 0.001). CLTM and LETM can also be found in MOG-AD patients. The presence of CLTM (sensitivity and specificity: 95.65% and 69.56%), possessed higher sensitivity and specificity for NMO diagnosis than LETM presence (sensitivity and specificity: 78.26% and 43.47%). CONCLUSION: A diagnostic criteria including the centrality, location, and expansion of the transverse myelitis lesions, in addition to LETM, may be more accurate in the diagnosis of NMOSD and MOG-AD and their distinction from MS.

The Effects of Sesquiterpene Lactones on the Differentiation of Human or Animal Cells Cultured In-Vitro: A Critical Systematic Review.

Cellular differentiation is pivotal in health and disease. Interfering with the process of differentiation, such as inhibiting the differentiation of adipocytes and inducing the differentiation of cancer cells, is considered a therapeutic approach. Sesquiterpene lactones, primarily found in plants, have been attracted attention as differentiating/dedifferentiating agents tested on various human or animal cells. However, a consensus on sesquiterpene lactones' effects and their mechanism of action is required. In this sense, through a systematic review, we have investigated the differentiating/dedifferentiating effects of sesquiterpene lactones on human or animal cells. 13 different cell lines originated from humans, mice, and rats, in addition to the effects of a total of 21 sesquiterpene lactones, were evaluated in the included studies. These components had either inducing, inhibiting, or no effect on the cells, mediating their effects through JAK-STAT, PI3K-Akt, mitogen-activated protein kinases, NFκB, PPARγ pathways. Although nearly all inducing and inhibiting effects were attributed to cancerous and normal cells, respectively, this is likely a result of a biased study design. Few studies reported negative results along with others, and no study was found reporting only negative results. As a result, not only are the effects and mechanism of action of sesquiterpene lactones not vivid but our knowledge and decisions are also misconducted. Moreover, there is a significant knowledge gap regarding the type of evaluated cells, other sesquiterpene lactones, and the involved signaling pathways. In conclusion, sesquiterpene lactones possess significant effects on differentiation status, leading to potentially efficient therapy of obesity, osteoporosis, and cancer. However, reporting negative results and further investigations on other cells, sesquiterpene lactones, and signaling pathways are highly suggested to pave the path of sesquiterpene lactones to the clinic more consciously.

Covid-19 in Parkinson's Disease treated by drugs or brain stimulation.

PURPOSE: Covid-19 has affected all people, especially those with chronic diseases, including Parkinson's Disease (PD). Covid-19 may affect both motor and neuropsychiatric symptoms of PD patients. We intend to evaluate different aspects of Covid-19 impact on PD patients. METHODS: 647 PD patients were evaluated in terms of PD-related and Covid-19-related clinical presentations in addition to past medical history during the pandemic through an online questioner. They were compared with an age-matched control group consist of 673 individuals and a sample of the normal population consist of 1215 individuals. RESULTS: The prevalence of Covid-19 in PD patients was 11.28%. The mortality was 1.23% among PD patients. The prevalence of Covid-19 in PD patients who undergone Deep Brain Stimulation (DBS) was 18.18%. No significant association was found between the duration of disease and the prevalence of Covid-19. A statistically significant higher prevalence of Covid-19 in PD patients who had direct contact with SARS-CoV-19 infected individuals was found. No statistically significant association has been found between the worsening of motor symptoms and Covid-19. PD patients and the normal population may differ in the prevalence of some psychological disorders, including anxiety and sleeping disorders, and Covid-19 may affect the psychological status. CONCLUSION: PD patients possibly follow tighter preventive protocols, which lead to lower prevalence and severity of Covid-19 and its consequences in these patients. Although it seems Covid-19 does not affect motor and psychological aspects of PD as much as it was expected, more accurate evaluations are suggested in order to clarify such effects.