Philadelphia College of Osteopathic Medicine
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Synthesis, structural characterization, and inhibitory effects of caffeic acid phenethyl ester (CAPE) derivatives on human multiple myeloma cell growth
No full textMultiple Myeloma (MM) is a hematologic cancer that develops due to the proliferation of malignant plasma cells in bone marrow. The accumulation of MM cells leads to a variety of complications such as anemia, bone disease, and renal damage. Despite advancements in technology and improvements in chemotherapy and stem cell transplantation, MM remains challenging to treat due to its drug resistance and the associated side effects, leading researchers to explore naturally derived compounds as adjuvant with current treatments. Caffeic acid phenethyl ester (CAPE), found in honeybee propolis, has demonstrated various pharmacological properties including anti-cancer effects. Previous studies have reported that CAPE and its derivatives inhibit the growth of MM cells through the induction of apoptosis and oxidative stress. This study investigates the inhibitory effects, mechanisms of action, and structural modifications associated with CAPE derivatives in MM cell growth.
Five new CAPE derivatives were synthesized and characterized. RPMI 8226 (MM) cells were treated with CAPE and these derivatives to evaluate their cytotoxic effects using presto blue assay. Cytotoxic activity of CAPE and its derivatives in the presence of ferroptosis inducer and inhibitor, erastin and ferrostatin-1, were also determined to investigate the involvement of ferroptosis. Western blot analysis of RPMI 8226 cell lysates was used to examine the expression of the apoptotic marker, caspase 3, and ferroptosis markers, GPX4 and CHAC1. The structural modification of each CAPE derivative was assessed to identify which modification yields a greater or lesser inhibitory effect on MM cell growth.
CAPE derivatives were evaluated for their effects on RPMI 8226 cell viability, resulting in a reduction in cell viability. Western blot analysis showed that while CAPE induces apoptosis, it is not the only mechanism of cell death for CAPE derivatives, prompting further investigation into their potential link to ferroptosis. When combined with the ferroptosis inducer, a significant reduction in cell viability was observed. In contrast, no significant effect occurred with the ferroptosis inhibitor, ferrostatin-1. Additionally, Western blot analysis showed a notable decrease in GPX4 expression and increased CHAC1 expression when combined with Erastin. The opposite results were seen when the derivatives were combined with Ferrostatin-1, with an increase in GPX4 expression and a decrease in CHAC1 expression.
The results from the experiment confirmed the inhibitory effects of CAPE derivatives on MM RPMI 8226 cells, consistent with findings from previous studies. Ferroptosis induction may serve as the main mechanism behind the inhibitory effects of CAPE derivatives compared to apoptosis induction. The structure-activity relationship of CAPE and its derivatives reveals that replacing the ester group with an amide result in a stronger cell death response, as seen in two derivatives compared to CAPE. These data highlight how structural modifications can either preserve or diminish CAPE\u27s effects, emphasizing the critical role of structural changes in modulating its activity
Infections with Chlamydia pneumoniae and SARS-CoV-2 and Alzheimer\u27s disease pathogenesis
Full text linkINTRODUCTION: Alzheimer\u27s disease (AD) is the most prevalent neurodegenerative disease in the world, but our understanding of causation is still lacking. A current evidence-based hypothesis proposes that certain infectious agents initiate the neurodegeneration consistent with AD. Two infectious agents correlated to AD pathogenesis are Chlamydia pneumoniae (Cpn), a respiratory obligate intracellular bacterium, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus responsible for the COVID-19 pandemic. Both organisms may predispose susceptible populations to disease manifestations, such as AD.
METHODS: This review focused on peer-reviewed original research and review articles evaluating the potential association of Cpn and SARS-CoV-2 with AD. Our focus included: genetic risk with expression of APOEε4 and other biomarkers common to AD including interleukin-6 (IL-6), chemokine ligand 2 (CCL2), neuropilin-1 (NRP1), and structural/functional aspects of the infectious processes and resultant neuroinflammation.
RESULTS: Both Cpn and SARS-CoV-2 may infect the neuroepithelium of the olfactory system to enter the brain. Cpn binds to heparan sulfate proteoglycans for entry into mucosal cells. SARS-CoV-2 infects epithelia after binding to ACE2 receptors. Once inside the neuroepithelium, the pathogens may traffic to the olfactory bulbs. NRP1, an abundant receptor in AD, also potentiates SARS-CoV-2 infection. Furthermore, both pathogens may enter the systemic circulation for eventual entry through the blood brain barrier. The SARS-CoV-2 spike protein, in conjunction with CCL2, co-stimulates macrophages, resulting in IL-6 cytokine release. Likewise, Cpn infection leads to an increase of CCL2 and IL-6 cytokine release. The primary infection of either organism may lead to chronically elevated levels of IL-6 and secondary infection(s). Additionally, host APOEε4 expression appears to increase susceptibility to Cpn and SARS-CoV-2 infections.
DISCUSSION: Cpn and SARS-CoV-2 may enter the brain through olfactory neuroepithelial cells and/or through the blood brain barrier. SARS-CoV-2 utilizes specific receptors for infection, while Cpn utilizes binding of proteoglycans. Neuroinflammation may be an outcome of infection with one or both organisms as observed by increased levels of CCL2 and IL-6 leading to AD pathogenesis. Genetic risk is noted for infection with both organisms with expression of APOEε4. Ongoing and future studies will further dissect mechanisms of infection with SARS-CoV-2 and Cpn as they may inform on causation and diagnostic factors for AD
Supervision of licensure-seeking counselors: what do seasoned supervisors think?
No full textUtilizing an exploratory sequential mixed methods design, we examined 11 seasoned supervisors’ cognitive structures while supervising licensure-seeking counselors in Virginia. Concept mapping revealed five supervision areas: supervisee’s counseling skills and clinical practice, supervisee’s reflexivity for personal and professional growth, supervisor’s preparation and intentional reflection on their practice, supervisory relationship and professional practice and housekeeping. These areas reflected systematic thinking aligned with prior findings on expert supervisors and highlighted practical nuances specific to advanced supervisees. The findings correspond closely with the cohesive model of supervision, supporting its relevance across training levels and utility as an empirically grounded framework for supervisory practice
A historic case of relapsing-remitting Alzheimer\u27s disease in an adolescent attributed to scarlet fever.
Full text linkWe draw attention to a historic case of a boy who suffered from scarlet fever (typically caused by the bacterium Streptococcus pyogenes) at age 7 years and went on to develop the symptoms of Alzheimer\u27s disease (AD). His physicians believed that the subsequent dementia was related to the infection. After death at 24 years of age, postmortem brain examination revealed abundant AD-type senile plaques and fibrils, formally confirming AD. Other potential causes of early-onset dementia are discussed, but these are distinct from patient E.H. This case is pertinent regarding the current debate about the potential role of infection in AD
Literature Review of Stiff Person Syndrome
Full text linkBackground: Stiff Person Syndrome (SPS) is a rare, debilitating autoimmune neurological disorder characterized by progressive muscle rigidity, painful spasms, and gait disturbances. It is strongly associated with autoantibodies against glutamic acid decarboxylase (GAD), leading to impaired GABAergic neurotransmission. SPS exists on a spectrum, with both classical and paraneoplastic variants, the latter often linked to malignancies such as breast cancer.
Methods: This review synthesizes current literature on the pathophysiology, clinical presentation, diagnostic criteria, and treatment modalities of SPS. We examine emerging therapies, including immunomodulatory approaches and antibody-targeted interventions, to address the heterogeneity of disease progression and treatment response.
Results: SPS remains a diagnostic challenge due to its overlap with other neuromuscular and psychiatric conditions. While anti-GAD65 antibodies serve as a key biomarker, seronegative cases complicate definitive diagnosis. Benzodiazepines and baclofen provide symptomatic relief, whereas intravenous immunoglobulin (IVIG) and plasmapheresis offer immunotherapeutic benefits. Novel treatments, including chimeric antigen receptor (CAR) T-cell therapy and extracorporeal photopheresis, present promising avenues for long-term disease management.
Conclusion: Advances in autoimmune neurology continue to refine our understanding of SPS, yet significant gaps persist in early diagnosis and individualized treatment strategies. A multidisciplinary approach integrating neurology, immunology, and psychiatry is imperative to improve clinical outcomes. Future research should focus on targeted immunotherapies and biomarker discovery to enhance prognosis and quality of life for affected individuals
Keynote
No full textDr. Sean Xin, DO, is a board-certificated neurosurgeon specializing in brain and tumor surgery, neuro-oncology, and spine surgery at Mercy Health in Toledo, Ohio. He completed his medical degree at Western University of Health Sciences, his neurosurgical residency at PCOM, and advanced fellowship training at City of Hope National Medical Center. Dr. Xin is committed to delivering expert, compassionate care tailored to each patient
Altered dendritic distribution of EPS8 after in vitro seizure-like activity in rat hippocampal neurons
No full textINTRODUCTION: Early-life seizures (ELS) often precede the onset of cognitive comorbidities. Prior studies have linked cognitive disorders with altered structural plasticity, the neuronal activity-dependent changes in neuronal structure. Specifically, plasticity changes linked to cognitive deficits are often at the level of dendritic spines, small protrusions off the dendrite that are the postsynaptic sites of most excitatory synapses in the brain. However, the underlying molecular mechanisms linking seizures to structural plasticity changes are not fully understood.
OBJECTIVES: The primary objective of this study was to determine if in vitro seizure-like activity in hippocampal neurons changes the distribution of epidermal growth factor receptor pathway substrate 8 (EPS8), an actin-capping protein that regulates the polymerization of the dendritic spine actin cytoskeleton, and therefore dendritic spine morphology. We have previously shown dendritic spine structural plasticity changes after induction of seizure-like activity in day in vitro (DIV17) neurons, and that spine density changes were dependent on when seizure-like activity was induced. We hypothesized that inducing seizure-like activity in rat hippocampal neurons would change distribution of EPS8 within the dendrite and dendritic spine, and that the EPS8 changes would correlate with spine density and structural plasticity change.
METHODS: We induced seizure-like activity in cultured rat hippocampal neurons with a zero Mg2+ solution at DIV10, 14, or 17. Cells were transfected with CellLight™ Actin-GFP, BacMam 2.0 (Invitrogen) to label actin, then fixed 1 hour, 3 days, or 7 days after seizure-like activity (DIV10+0, +3, or +7, for example). EPS8 was detected in fixed cells using immunocytochemistry. Labeling was imaged with a confocal microscope, then images were analyzed in ImageJ to determine EPS8 concentration ratio of dendritic spine:shaft in neurons exposed to zero Mg2+ compared to untreated controls by t-test.
RESULTS: Our preliminary results show that the EPS8/GFP spine:shaft ratio of DIV10 neurons decreases in zero Mg2+ groups when compared to control groups immediately after seizure-like activity, representing a decreased EPS8 protein concentration at dendritic spines compared to the dendritic shaft. The EPS8 was more evenly distributed throughout the dendrite in contrast to control groups, which exhibit a preference for EPS8 accumulation in the dendritic spines. EPS8/GFP spine:shaft ratio rebounds within 3 days, by DIV10+3. The EPS8/GFP spine:shaft ratio remains elevated through day 7 (DIV10+7). We did not see a change in EPS8/GFP spine:shaft ratio when seizure-like activity was induced at DIV14. Interestingly, three days after seizure-like activity was induced at DIV17 (DIV17+3), a time point at which we previously showed an inability to induce dendritic spine structural plasticity, we found a significant decrease in EPS8/GFP spine:shaft ratio compared to control neurons.
CONCLUSION: These results suggest that early seizure-like activity alters the timeline of EPS8 dispersion throughout dendritic spines, potentially contributing to seizure-activity induced changes in dendritic spine structural plasticity and morphology
Bridging the gap in rural African American cardiovascular health: The intersection of nutrition, cultural competency, and preventative interventions
No full textIntroduction Cardiovascular disease (CVD) remains the leading cause of mortality in the United States, disproportionately affecting African Americans, particularly those in rural communities. Structural disparities, including limited healthcare access, socioeconomic barriers, and a lack of culturally competent nutritional guidance, exacerbate CVD risk. This study explores the impact of the African Heritage Diet, Culinary Medicine, and Community-based interventions on CVD prevention and management. The research seeks to answer: How do culturally tailored nutrition interventions and community-based health strategies impact CVD prevention and management in rural African American populations?
Methods A systematic literature review was conducted to analyze current research on CVD disparities, nutrition, and intervention strategies. Key areas of investigation included:
Comparative effectiveness of the Dietary Approaches to Stop Hypertension (DASH) diet versus the African Heritage Diet.
Evaluation of culinary medicine as a behavioral intervention in improving dietary adherence and long-term health outcomes.
Assessment of community-driven programs, including faith-based health initiatives, mobile health clinics, telemedicine, and local agricultural partnerships.
Results & Discussion Findings suggest that nutrition-based interventions incorporating cultural familiarity improve dietary adherence and effectiveness. The African Heritage Diet, rooted in traditional heritage while combining historical dietary patterns, may enhance patient compliance. Culinary medicine interventions further reinforce sustainable dietary behaviors by integrating hands-on, culturally relevant nutrition education.
Additionally, Community-based health programs significantly enhance healthcare accessibility. Faith-based initiatives and mobile health clinics provide trusted, localized care, while telemedicine and food accessibility programs address logistical barriers to health management. Despite these benefits, several challenges persist, including limited rural healthcare infrastructure, the need for culturally competent dietary recommendations, and a lack of large-scale implementation studies.
Conclusion & Future Directions Culturally tailored dietary interventions and community-driven healthcare models show promise in reducing CVD disparities among rural African Americans. Future research should focus on the scalability and long-term sustainability of these interventions. Policy-driven solutions, such as expanding funding for mobile health services and integrating cultural competency training in medical curriculum, are necessary to bridge existing healthcare gaps. Addressing these structural challenges will be critical in improving cardiovascular health outcomes in underserved populations
Effect of Talocrural Joint Manipulation on pain sensitivity for Patients with Achilles Tendinopathy
No full textBackground and Introduction
Recent research indicates that a significant proportion of the benefits of manual therapy arise from neurophysiologic effects, rather than strictly mechanical means. There has, however, been little published literature specific to lower extremity tendinopathies to inform providers about expected neurophysiologic/sensory changes. This research seeks to build knowledge specific to the changes that manual therapy can effect in individuals with Achilles tendinopathy, specifically heat and cold pain thresholds. This study is relevant due to the high prevalence of Achilles tendon pain, coupled with the current documented challenges in the treatment of this population.
Methods
36 adult subjects with Achilles tendon pain for at least 3 months. Individuals were excluded if the involved lower leg had any surgical history, had a steroid injection in the affected area within 6 months, were currently pregnant, or had a connective tissue disorder. A baseline assessment of heat and cold pain thresholds was performed following accepted protocols. Three trials of each test were completed. Subjects assigned to the intervention group received a talocrural joint high velocity, low amplitude manipulation. The control group received a plausible sham of passive ankle movement without moving to the end ranges. Immediately following the application of the intervention or sham all participants were re-tested for heat and cold pain thresholds.
Results
Contrary to the initial hypothesis, neither the treatment nor sham groups showed improved pain thresholds to heat or cold. In contrast, the intervention group showed a trend toward worsened heat tolerances (paired t-test p=.015).
No statistically significant changes were found in the intervention group\u27s cold response nor with either heat or cold in the control group.
Though the primary hypothesis was not confirmed, this research did produce more robust normative data for heat and cold pain thresholds in this population than previously has been published. In this sample of 36 individuals, mean heat pain threshold was 44.51℃ SD=3.22 and cold pain threshold was 9.39℃ SD=10.56.
Conclusion
This research found data contrary to existing theoretical frameworks which had shown a pattern of improvement in pain sensitivity after manual therapy. Several possible explanations exist for this difference, primarily that this specific combination of population, intervention, and outcome assessment had not been previously tested in the identified literature. Additionally, it is conceivable that the manual pressure applied with the intervention could have provided unintended secondary responses influencing pain.
This research did, however, improve upon existing data on normative pain thresholds for individuals with persistent Achilles pain, in that while the means identified in this data were similar, the sample size was larger than other studies found in published literature.
The clinical implications of this research are two-fold, first, it found no improvement in heat or cold pain thresholds in subjects receiving manual therapy compared to those with a sham. Secondly, these findings significantly strengthen the existing dataset related to normative pain thresholds in individuals with Achilles tendon pain