Attenuation of Inflammatory Responses in Breast and Ovarian Cancer Cells by a Novel Chalcone Derivative and Its Increased Potency by Curcumin.

Background: Breast and ovarian cancers are two common malignancies in women and a leading cause of death globally. The aim of the present study was to explore the effects of a novel chalcone derivative 1-(4-(methylsulfonyl)phenyl)-3-(phenylthio)-3-(p-tolyl)propane-1-one (MPP) individually or combined with curcumin, a well-known herbal medicine with anticancer properties, as a new combination therapy on inflammatory pathways in breast and ovarian cancer cell lines. Methods: LPS-induced NF-κB DNA-binding activity and the levels of proinflammatory cytokines were measured in the MPP- and MPP-curcumin combination-treated MDA-MB-231 and SKOV3 cells by ELISA-based methods. The expression of COX2, INOS, and MMP9 genes and nitrite levels was also evaluated by real-time qRT-PCR and Griess method, respectively. IκB levels were evaluated by Western blotting. Results: MPP significantly inhibited the DNA-binding activity of NF-κB in each cell line and subsequently suppressed the expression of downstream genes including COX2, MMP9, and INOS. The levels of proinflammatory cytokines, as well as NO, were also decreased in response to MPP. All the effects of MPP were enhanced by the addition of curcumin. MPP, especially when combined with curcumin, caused a remarkable increase in the concentration of IκB. Conclusion: MPP and its coadministration with curcumin effectively reduced the activity of the NF-κB signaling pathway, leading to a reduced inflammatory response in the environment of cancer cells. Thus, MPP, either alone or combined with curcumin, might be considered an effective remedy for the suppression of inflammatory processes in breast and ovarian cancer cells.

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.

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.

Prevalence of coronavirus disease 2019 in patients with neuromyelitis optica in Isfahan, Iran, and a review on recent reports and literature.

Background: Despite many studies, it is still unclear how patients with neuromyelitis optica spectrum disorder (NMOSD) would respond to coronavirus disease 2019 (COVID-19). We conducted a research on prevalence of COVID-19 in patients with NMOSD in Isfahan, Iran. We have also reviewed the recent publications on this issue. Methods: 149 patients with NMOSD who were under medications were monitored for confirmed cases of COVID-19. Prevalence of COVID-19 in addition to mean age, mean duration of disease, and mean age of onset of infected patients and uninfected patients were calculated via Microsoft Excel software. Results: The prevalence of COVID-19 in studied patients with NMOSD was 5.37%. Mean age, mean duration of disease, and mean age of onset of eight patients (male to female ratio: 1:3) diagnosed with COVID-19 were 33.62 ± 5.20 years, 6.87 ± 6.05 years, and 26.75 ± 6.94 years, respectively, while they were 39.97 ± 11.37 years, 7.50 ± 3.91 years, and 32.46 ± 11.29 years for uninfected patients with NMOSD (n = 141). No significant association was observed between the type of medications and prevalence of COVID-19 (P > 0.05). Conclusion: There is not a consensus in the literature on the prevalence of COVID-19 in patients with NMOSD and the effect of NMOSD medications on susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The prevalence of COVID-19 in our sample was 5.37%. The impact of the kind of NMOSD medication on the prevalence of COVID-19 in patients with NMOSD was found to be insignificant. Moreover, the infected patients were relatively younger, and their disease started earlier in comparison to uninfected patients.

Case series: New-onset freezing of gait in combined use of deep brain stimulation and Levodopa.

Concurrent use of DBS and levodopa in Parkinson's disease patients can lead to freezing of gait. This phenomenon may be due to an inverted-U-Shaped function of dopamine.

Parkinson's disease patients may have higher rates of Covid-19 mortality in Iran.

BACKGROUND: Parkinson's disease (PD) patients may be at increased risk of Covid-19 mortality due to the nature of their disease or underlying conditions. METHOD: The information of 12,909 Covid-19 patients who were hospitalized during the last eleven months were collected from the data depository of two referral university hospitals. Eighty-seven of these patients were diagnosed with PD, and thirty-one of these PD patients died because of Covid-19. 2132 other deaths occurred in these centers, related to Covid-19 of non-PD patients. Fisher exact test, Chi-square test, and Principle component analysis were used for statistical analysis. RESULTS: The mortality among PD patients and other hospitalized patients was 35.6% and 19.8%, respectively, and the difference between the mortality of these two groups was found to be statistically significant (p-value<0.01). The mean age of PD patients who passed away was 77.06 ± 7.46, and it was not significantly different from that of alive PD patients (p-value>0.05). Alzheimer's disease as an underlying condition was more frequent in deceased PD patients in comparison to survived PD patients, and this difference was found to be statistically significant (p-value<0.01). CONCLUSION: PD patients possess a higher rate of Covid-19 mortality in comparison with other patients hospitalized for Covid-19. PD pathophysiology, advanced age, underlying conditions, and health systems' efficacy may play an essential role in such an outcome.

Deep brain stimulation of anteromedial globus pallidus internus improved OCD rather than tics in a Gilles de la Tourette syndrome patient.

A 32-year-old gentleman with refractory Gilles de la Tourette syndrome went on a DBS procedure on anteromedial globus pallidus internus. At the most suitable adjustment, the OCD component of his disease improved almost completely while his tics remained unchanged which was in contrast with other previous studies. Moreover, variations in symptoms were seen in response to different adjustments. We discuss that these variations and fluctuations in the therapeutic outcomes may be due to differences in physiological conditions of tic- or OCD-specified pathways and areas including distinct stimulation threshold and occurrence of neuroplasticity in neural circuits which may determine the responsiveness of each pathway or circuit to a specific stimulus. At last, we suggest that pathways and circuits should be targeted for DBS rather than single components; as these components may be involved in multiple pathways, related to different pathophysiological states.

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.