Korean Black Goat Extract Exerts Estrogen-like Osteoprotective Effects by Stimulating Osteoblast Differentiation in MC3T3-E1 Cells and Suppressing Osteoclastogenesis in RAW 264.7 Cells.

Postmenopausal osteoporosis, characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-driven bone formation, presents substantial health implications. In this study, we investigated the role of black goat extract (BGE), derived from a domesticated native Korean goat, estrogen-like activity, and osteoprotective effects in vitro. BGE's mineral and fatty acid compositions were analyzed via the ICP-AES method and gas chromatography-mass spectrometry, respectively. In vitro experiments were conducted using MCF-7 breast cancer cells, MC3T3-E1 osteoblasts, and RAW264.7 osteoclasts. BGE exhibits a favorable amount of mineral and fatty acid content. It displayed antimenopausal activity by stimulating MCF-7 cell proliferation and augmenting estrogen-related gene expression (ERα, ERß, and pS2). Moreover, BGE positively impacted osteogenesis and mineralization in MC3T3-E1 cells through Wnt/ß-catenin pathway modulation, leading to heightened expression of Runt-related transcription factor 2, osteoprotegerin, and collagen type 1. Significantly, BGE effectively suppressed osteoclastogenesis by curtailing osteoclast formation and activity in RAW264.7 cells, concurrently downregulating pivotal signaling molecules, including receptor activator of nuclear factor κ B and tumor necrosis factor receptor-associated factor 6. This study offers a shred of preliminary evidence for the prospective use of BGE as an effective postmenopausal osteoporosis treatment.

Race-Related Differences in Sipuleucel-T Response among Men with Metastatic Castrate-Resistant Prostate Cancer.

Sipuleucel-T is an autologous cellular immunotherapy that targets prostatic acid phosphatase (PAP) and is available for treatment of men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). In this single-arm, two-cohort, multicenter clinical study, potential racial differences in immune responses to sipuleucel-T in men with mCRPC were explored. Patients' blood samples were obtained to assess serum cytokines, humoral responses, and cellular immunity markers before and after treatment. Baseline cumulative product parameters (total nucleated and CD54+ cell counts and CD54 upregulation) were evaluated. IgM titers against the immunogen PA2024, the target antigen PAP, prostate-specific membrane antigen (PSMA) and prostate-specific antigen (PSA) were quantified by ELISA. Cytotoxic T-lymphocyte activity was determined by ELISpots, and cytokine and chemokine concentrations were determined by Luminex.Twenty-nine African American (AA) men and 28 non-African American (non-AA) men with mCRPC received sipuleucel-T. Baseline total nucleated cell count, CD54+ cell count, CD54 expression, and cumulative product parameters were higher in non-AA men. Although PSA baseline levels were higher in AA men, there were no racial differences in IgM antibody and IFNγ ELISpots responses against PA2024, PAP, PSA, and PSMA before and after treatment. Expression of co-stimulatory receptor ICOS on CD4+ and CD8+ T cells, and the levels of Th1 cytokine granulocyte-macrophage colony-stimulating factor and chemokines CCL4 and CCL5, were significantly higher in AA men before and/or after treatment. Despite no difference in the overall survival, PSA changes from baseline were significantly different between the two races. The data suggest that immune correlates in blood differ in AA and non-AA men with mCRPC pre- and post-sipuleucel-T. SIGNIFICANCE: Our novel findings of higher expression of co-stimulatory receptor ICOS on CD4+ and CD8+ T cells in African American patients with metastatic castrate-resistant prostate cancer (mCRPC) prior and post-sipuleucel-T suggest activation of CD4+ and CD8+ T cells. The data indicate that racial differences observed in these and other immune correlates before and after sipuleucel-T warrant additional investigation to further our understanding of the immune system in African American men and other men with mCRPC.

Effects of a human amniotic membrane extract on ARPE-19 cells.

BACKGROUND: Human Amniotic Membrane (hAM) is endowed with several biological activities and might be considered an optimal tool in surgical treatment for different ophthalmic pathologies. We pioneered the surgical use of hAM to treat retinal pathologies such as macular holes, tears, and retinal detachments, and to overcome photoreceptor damage in age-related macular degeneration. Although hAM contributed to improved outcomes, the mechanisms of its effects are not yet fully understood. The characterization and explanation of the effects of hAM would allow the adoption of this new natural product in different retinal pathologies, operative contexts, and hAM formulations. At this end, we studied the properties of a hAM extract (hAME) on the ARPE-19 cells. METHODS AND RESULTS: A non-denaturing sonication-based technique was developed to obtain a suitable hAME. Viability, proliferation, apoptosis, oxidative stress, and epithelial-mesenchymal transition (EMT) were studied in hAME-treated ARPE-19 cells. The hAME was able to increase ARPE-19 cell viability even in the presence of oxidative stress (H2O2, TBHP). Moreover, hAME prevented the expression of EMT features, such as EMT-related proteins, fibrotic foci formation, and migration induced by different cytokines. CONCLUSIONS: Our results demonstrate that the hAME retains most of the properties observed in the whole tissue by others. The hAME, other than providing a manageable research tool, could represent a cost-effective and abundant drug to treat retinal pathologies in the future.

Impact of extramedullary multiple myeloma on outcomes with idecabtagene vicleucel.

Idecabtagene vicleucel (Ide-cel) has demonstrated excellent efficacy and durable responses in patients with relapsed/refractory multiple myeloma (RRMM). However, the outcomes with ide-cel in patients with extramedullary disease (EMD) remain incompletely characterized. We included patients with RRMM treated with ide-cel between May 2021 and April 2023 across 11 US academic institutions. Visceral or soft tissue lesions non-contiguous from bone was classified as EMD. Time-to-event analyses were performed from date of ide-cel infusion. Among 351 patients, 84 (24%) had EMD prior to infusion. The median follow-up from ide-cel infusion was 18.2 months (95% CI: 17-19.3). The day 90 overall response rates (ORR) were 52% vs. 82% for the EMD and non-EMD cohorts, respectively (p < 0.001). The median progression-free survival (PFS) was 5.3 months (95% CI: 4.1-6.9) for the EMD cohort vs. 11.1 months (95% CI: 9.2-12.6; p < 0.0001) for the non-EMD cohort. In a multivariable analysis, EMD was an independent predictor of inferior PFS [hazard ratio 1.5 (1.1-2.2), p = 0.02]. The median overall survival was 14.8 months [95% CI: 9-Not reached (NR)] vs. 26.9 months (26.3 vs. NR, p = 0.006) for the EMD and non-EMD cohorts, respectively. Extramedullary disease represents an independent predictor of inferior day 90 ORR and PFS among patients treated with ide-cel.

Absolute Lymphocyte Count and Outcomes of Multiple Myeloma Patients Treated with Idecabtagene Vicleucel: The US Myeloma Immunotherapy Consortium Real- World Experience.

Idecabtagene vicleucel (ide-cel) has shown impressive efficacy in relapsed/refractory multiple myeloma (RRMM). This study aimed to investigate the impact of absolute lymphocyte count (ALC) on the survival outcomes of RRMM patients treated with standard of care (SOC) ide-cel. Data were collected retrospectively from 11 institutions in the U.S. Impact of ALC parameters including pre-apheresis (pre-A), pre-lymphodepletion (pre-LD), absolute and percent difference from pre-A to pre-LD on clinical outcomes after ide-cel were examined using survival analysis. A new ALC profile was created based on univariate analysis that comprises 3 groups: normal (≥1 × 109/L) pre-LD ALC (LDN), low (<1 × 109/L) pre-LD ALC (LDL) + percent reduction <37.5 (%RL), and LDL ALC + percent reduction ≥37.5 (%RH). A total of 214 SOC ide-cel recipients were included in this analysis. The median patient age was 64 years (interquartile range [IQR], 57 to 69 years), median number of prior therapies was 6 (IQR, 5 to 9), and median duration of follow-up was 5.4 months (IQR, 2.1 to 8.3 months). Most patients had both low pre-A ALC (75.3%) and pre-LD ALC (77.2%), and the reduction from pre-A to pre-LD (median, .65 to .55 × 109/L) was statistically significant. Univariate analysis showed that the LDL + %RH group had significantly worse progression-free survival (PFS) and overall survival (OS) compared to the LDL + %RL and LDN ALC groups (6-month PFS: 40% versus 67.6% and 60.9%; 6-month OS: 69.5% versus 87% and 94.3%). In multivariable analysis, after adjusting for age, performance status, cytogenetic risk, use of bridging therapy, and extramedullary disease, PFS did not maintain its statistical significance; however, OS remained significantly worse for LDL + %RH group compared to the LDN ALC group (hazard ratio [HR], 4.3; 95% confidence interval [CI], 1.1 to 17), but the difference between the LDL + %RH versus %RL groups was not statistically significant (HR, 1.7; 95% CI, .8 to 4.0). Our findings indicate that low pre-LD ALC with high %R from pre-A to pre-LD was associated with inferior survival outcomes, particularly OS, in patients who received SOC ide-cel.

Safety of deer antler extract in children: A 12-week randomized controlled clinical trial.

BACKGROUND: Deer antlers have been used as strong tonifying medicine in Asian countries, especially for the growth and development of children in pediatrics of Korean medicine. The safety of deer antler in adults cannot be applied directly to children because of their physiological characteristics. To accumulate reliable data on the safety of deer antler in pediatric populations, well-designed clinical studies are required. METHODS: This research is a 12-week, randomized, double-blind, placebo-controlled clinical trial evaluating the safety of deer antler extract (DAE) in children. The DAE group received an intervention containing 1586 mg of DAE, whereas the control group received a placebo for 12 weeks. The safety was assessed by monitoring adverse drug reactions (ADRs) and laboratory test results. RESULTS: One hundred participants were included in the safety analysis. Three and 2 participants in the DAE and control groups, respectively, reported ADRs. There was no significant difference in incidence between the 2 groups. ADRs are categorized into gastrointestinal and skin-related symptoms. No serious ADR was observed throughout the study. The laboratory test results were within or outside the normal range at clinically insignificant levels. CONCLUSION: The research discovered that the DAE is safe in terms of ADRs and laboratory parameters under the conditions studied. Further studies are required to accumulate safety data about DAE dosage adjustment and potential interactions with other medicines.

Pilose antler extract promotes hair growth in androgenic alopecia mice by promoting the initial anagen phase.

Androgenetic alopecia (AGA) is a prevalent disease in worldwide, local application or oral are often used to treat AGA, however, effective treatments for AGA are currently limited. In this work, we observed the promoting the initial anagen phase effect of pilose antler extract (PAE) on hair regeneration in AGA mice. We found that PAE accelerated hair growth and increased the degree of skin blackness by non-invasive in vivo methods including camera, optical coherence tomography and dermoscopy. Meanwhile, HE staining of sagittal and coronal skin sections revealed that PAE augmented the quantity and length of hair follicles, while also enhancing skin thickness and hair papilla diameter. Furthermore, PAE facilitated the shift of the growth cycle from the telogen to the anagen phase and expedited the proliferation of hair follicle stem cells and matrix cells in mice with AGA. This acceleration enabled the hair follicles to enter the growth phase at an earlier stage. PAE upregulated the expression of the sonic hedgehog (SHH), smoothened receptor, glioma-associated hemolog1 (GLI1), and downregulated the expression of bone morphogenetic protein 4 (BMP4), recombinant mothers against decapentaplegic homolog (Smad) 1 and 5 phosphorylation. This evidence suggests that PAE fosters hair growth and facilitates the transition of the growth cycle from the telogen to the anagen phase in AGA mice. This effect is achieved by enhancing the proliferation of follicle stem cells and matrix cells through the activation of the SHH/GLI pathway and suppression of the BMP/Smad pathway.

Neutrophil extracellular traps and active myeloperoxidase concentrate in lamellar tissue of equids with naturally occurring laminitis.

Laminitis is a pathology of the equine digit ultimately leading to a failure of the dermo-epidermal interface. Neutrophil activation is recognized as a major factor in SIRS-associated laminitis and has recently been described in induced endocrinopathic laminitis evidenced by the presence of myeloperoxidase (MPO). Neutrophil extracellular traps (NET) are released with neutrophil activation. This study aimed to investigate the presence and activity of MPO and NET in the lamellar tissue of equids presented with naturally occurring laminitis. Samples of lamellar tissue of five horses and five donkeys presented with laminitis, as well as eight control horses without laminitis, were collected. Lamellar tissue extracts were submitted to ELISA and specific immuno-extraction followed by enzymatic detection (SIEFED) assays to confirm the presence and activity of both MPO and NET. Lamellar sections were also immunohistopathologically stained for MPO and NET. Analysis of lamellar tissue extracts revealed that laminitis cases had significantly higher levels of total MPO concentration, MPO activity, and NET-bound MPO activity in comparison to control horses. Moreover, a strong correlation was identified between the activity of NET-bound MPO and the total MPO activity, which suggests that MPO activity partly originates from NET-bound MPO. Immunohistochemical staining showed that MPO and NET labelling in laminitis cases was moderate to marked, primarily in the epidermis and in inflammatory infiltrates containing neutrophils, while labelling in control horses was minimal. This article constitutes the first indication of the presence and activity of NET-bound MPO in the lamellar tissue of horses and donkeys with naturally occurring laminitis. Targeting these substances may provide new treatment possibilities for this debilitating disease.

High-Dimensional Analyses Reveal IL15 Enhances Activation of Sipuleucel-T Lymphocyte Subsets and Reverses Immunoresistance.

Sipuleucel-T (sip-T) is the only FDA-approved autologous cellular immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). To elucidate parameters of the response profile to this therapy, we report high-dimensional analyses of sip-T using cytometry by time of flight (CyTOF) and show a lymphoid predominance, with CD3+ T cells constituting the highest proportion (median ∼60%) of sip-T, followed by B cells, and natural killer (NK) and NKT cells. We hypothesized that treatment of sip-T with homeostatic cytokines known to activate/expand effector lymphocytes could augment efficacy against prostate tumors. Of the cytokines tested, IL15 was the most effective at enhancing activation and proliferation of effector lymphocytes, as well as augmenting tumor cytotoxicity in vitro. Co-culture of sip-T with IL15 and control or prostate-relevant antigens showed substantial activation and expansion of CD8+ T cells and NKT cells in an antigen-specific manner. Adoptive transfer of IL15-treated sip-T into NSG mice resulted in more potent prostate tumor growth inhibition compared with control sip-T. Evaluation of tumor-infiltrating lymphocytes revealed a 2- to 14-fold higher influx of sip-T and a significant increase in IFNγ producing CD8+ T cells and NKT cells within the tumor microenvironment in the IL15 group. In conclusion, we put forward evidence that IL15 treatment can enhance the functional antitumor immunity of sip-T, providing rationale for combining IL15 or IL15 agonists with sip-T to treat patients with mCRPC.

Advances in cancer vaccines for immunotherapy of prostate cancer / 中南大学学报(医学版)

Prostate cancer is currently one of the most common malignancies that endanger the lives and health of elderly men. In recent years, immunotherapy, which exploits the activation of anti-cancer host immune cells to accomplish tumor-killing effects, has emerged as a new study avenue in the treatment of prostate cancer. As an important component of immunotherapy, cancer vaccines have a unique position in the precision treatment of malignant tumors. Monocyte cell vaccines, dendritic cell vaccines, viral vaccines, peptide vaccines, and DNA/mRNA vaccines are the most often used prostate cancer vaccines. Among them, Sipuleucel-T, as a monocyte cell-based cancer vaccine, is the only FDA-approved therapeutic vaccine for prostate cancer, and has a unique position and role in advancing the development of immunotherapy for prostate cancer. However, due to its own limitations, Sipuleucel-T has not been widely adopted. Meanwhile, owing to the complexity of immunotherapy and the specificity of prostate cancer, the remaining prostate cancer vaccines have not shown good clinical benefit in large randomized phase II and phase III trials, and further in-depth studies are still needed.

Histopathological and immunohistochemical study of antiosteoporotic efficacy of the earthworm Allolobophora caliginosa extract in orchiectomized rats / Estudio histopatológico e inmunohistoquímico de la eficacia antiosteoporótica del extracto de lombriz de tierra Allolobophora caliginosa en ratas orquiectomizadas

SUMMARY: Osteoporosis is a bone condition marked by a loss of bone mass and a disruption of bone microarchitecture. Men lose bone density as they age, resulting in brittle bones. The loss of free testosterone is one of the key factors. The objective of present study was to evaluate Allolobophora caliginosa extract (AcE) for its anti-osteoporotic and antiapoptotic activity in orchiotomized rat model at two different dose levels. Twenty eight male rats were divided into two groups. The first group represented sham operated rats while the second group underwent bilateral orchidectomy (OCX). After one week of recovery from orchidectomy surgery, the second group was randomly subdivided into 3 subgroups. The first OCX subgroup was administered orally distilled water daily for 10 weeks. The other two OCX subgroups were administered AcE (100 or200 mg/kg body weight/day) orally for 10 weeks. Orchiectomy induces remarkable loss of the cortical as well as trabecular bone loss; which, could be counterbalanced by Allolobophora caliginosa extract (AcE) that prevented cortical as well as trabecular bone loss. Allolobophora caliginosa extract (AcE) at Dose 200 mg/kg/day was found to be effective at a highly significant level in osteoporotic bone, as determined by histological images and immunohistochemical study, where Dose (100 mg/kg/day) was found to be moderately significant.In the present study, it is suggested that AcE may inhibit steroid-induced osteoblasts apoptosis, potentially via upregulation of Bcl-2 and downregulation of caspase-3. Allolobophora caliginosa extract demonstrates anti-apoptotic and anti-oxidant properties. Therefore, AcE may be used for the prevention of steroid-induced bone damage.

RESUMEN: La osteoporosis es una afección ósea caracterizada por una pérdida de masa ósea y una alteración de la microarquitectura ósea. Los hombres pierden densidad ósea a medida que envejecen, lo que resulta en huesos quebradizos. La pérdida de testosterona libre es factor clave en este proceso. El objetivo del presente estudio fue evaluar el extracto de Allolobophora caliginosa (AcE) debido a su actividad antiosteoporótica y antiapoptótica en un modelo de rata orquiectomizadas con dos niveles de dosis diferentes. Se dividieron veintiocho ratas macho en dos grupos. El primer grupo incluyó ratas con operación simulada, mientras que el segundo grupo se sometió a orquidectomía bilateral (OCX). Después de una semana de recuperación de la orquidectomía, el segundo grupo fue subdividido en 3 subgrupos. Al primer subgrupo de OCX se administró diariamente agua destilada por vía oral durante 10 semanas. Los otros dos subgrupos de OCX se administraron por vía oral AcE (100 o 200 mg / kg de peso corporal / día) durante 10 semanas. La orquidectomía induce una pérdida notable del hueso cortical y trabecular; el cual podría ser contrarrestado por el extracto de Allolobophora caliginosa (AcE) que previno la pérdida de hueso tanto cortical como trabecular visualizado en imágenes histológicas y estudio inmuno- histoquímico, donde se encontró que la dosis (100 mg / kg / día) era moderadamente significativa. En el presente estudio, se sugiere que la AcE puede inhibir la apoptosis de los osteoblastos inducida por esteroides, potencialmente a través de la regulación al alza de Bcl 2 y la regulación a la baja de caspasa 3. El extracto de Allolobophora caliginosa demuestra propiedades anti apoptóticas y antioxidantes. Por lo tanto, AcE puede usarse para la prevención del daño óseo inducido por esteroides.

Membrana amniótica, aplicaciones clínicas e ingeniería tisular. Revisión de su uso oftalmológico / Amniotic membrane, clinical applications and tissue engineering. Review of its ophthalmic use

La utilización de la membrana amniótica en la oftalmología está en alza en los últimos años debido a: sus múltiples propiedades biológicas y tectónicas, la mejora en el proceso de su obtención, la facilidad de uso y el avance en la ingeniería tisular. La membrana amniótica se ha convertido en uno de los principales tratamientos coadyuvantes, tanto en la cirugía oftalmológica como en otras especialidades médico-quirúrgicas. El desarrollo de la ingeniería tisular ha permitido su utilización no solo en su forma clásica sino también mediante gotas y otras presentaciones. A lo largo del artículo hemos realizado un resumen de los distintos pasos previos a su uso (preparación y conservación), de las distintas técnicas quirúrgicas y de sus principales aplicaciones clínicas

The use of amniotic membrane in ophthalmology has been increasing in recent years due to its multiple biological and tectonic properties, improvement in the process of obtaining, ease of use, and advancement in tissue engineering. The amniotic membrane has become one of the main adjuvant treatments, in ophthalmic surgery as well as in other medical-surgical specialties. The development of tissue engineering has allowed it to be used, not only in its classic form, but also by the use of drops and other presentations. The different steps prior to its use (preparation and conservation), the different surgical techniques, and their main clinical applications are described throughout the article

Effect of powdered shells treatment of the snail Megalobulimus lopesi on wounds of diabetic rats

Abstract Purpose: To analyzed the healing effect of the powdered shell of the Megalobulimus lopesi snail on wounds of diabetic rats, since in non-diabetic rats the powdered shell presented healing potential. Methods: Seventy-two Wistar rats (Rattus norvegicus albinus) were divided into three groups: Control group (GC.diab), no therapeutic intervention on the wound; Vehicle's Control group, topical via, in diabetic rats (GCvt.diab): Powder Shell Group (PC) applied topically (GPCvt.diab): Experimental group was administered topically shortly after wound dressing and once a day during the experimental period (3, 7, 14 and 21 days) the composition containing the powdered shell of the snail. The following variables related to the healing potential were analyzed: macroscopic one, where the capacity of reduction of the wound area was evaluated; histological analysis in HE, angiogenic activity, morphometric analysis (re-epithelization), leukocyte inflammatory infiltrate; leukocyte count and also differentiation in peripheral blood. Results: The topical application in wounds of diabetic rats presented healing activity, accelerating wound closure, stimulating angiogenesis and being pro-inflammatory in the early and anti-inflammatory stages in the final times of the healing process. Conclusion: The topical administration of the powdered shell on wounds of diabetic patients becomes a therapeutic option of low cost, with ease in the administration and access as well.

Differential Hrd1 Expression and B-Cell Accumulation in Eosinophilic and Non-eosinophilic Chronic Rhinosinusitis With Nasal Polyps

PURPOSE: Hrd1 has recently emerged as a critical regulator of B-cells in autoimmune diseases. However, its role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) remains largely unexplored. This study aimed to examine Hrd1 expression and B-cell accumulation and their possible roles in CRSwNP. METHODS: Quantitative real-time polymerase chain reaction, immunohistochemistry, enzyme-linked immunosorbent assay and Western blotting were used to assess gene and protein expression in nasal tissue extracts. Cells isolated from nasal tissues and peripheral blood mononuclear cells were characterized by flow cytometry. Local antibody production was measured in tissue extracts with a Bio-Plex assay. Additionally, changes in Hrd1 expression in response to specific inflammatory stimuli were measured in cultured dispersed polyp cells. RESULTS: Nasal polyps (NPs) from patients with eosinophilic CRSwNP (ECRS) had increased levels of Hrd1, B-cells and plasma cells compared with NPs from patients with non-eosinophilic CRSwNP (non-ECRS) or other control subjects (P < 0.05). The average Hrd1 levels in B-cells in NPs from ECRS patients were significantly higher than those from non-ECRS patients and control subjects (P < 0.05). NPs also contained significantly increased levels of several antibody isotypes compared with normal controls (P < 0.05). Interestingly, Hrd1 expression in cultured polyp cells from ECRS patients, but not non-ECRS patients, was significantly increased by interleukin-1β, lipopolysaccharide and Poly(I:C) stimulation, and inhibited by dexamethasone treatment (P < 0.05). CONCLUSIONS: Differential Hrd1 expression and B-cell accumulation between the ECRS and non-ECRS subsets suggests that they can exhibit distinct pathogenic mechanisms and play important roles in NP.

Beetle (Ulomoides dermestoides) fat improves diabetes: effect on liver and pancreatic architecture and on PPARgamma expression

Ulomoides dermestoides is a beetle traditionally consumed to treat diabetes. In this study, we performed a composition analysis of U. dermestoides to obtain the principal fractions, which were used to assess the effect on glycemia, liver and pancreatic architecture, and PPARγ and GLUT4 expression. Normal mice and alloxan-induced diabetic mice were administered fractions of chitin, protein or fat, and the acute hypoglycemic effect was evaluated. A subacute study involving daily administration of these fractions to diabetic mice was also performed over 30 days, after which the liver and pancreas were processed by conventional histological techniques and stained with hematoxylin and eosin to evaluate morphological changes. The most active fraction, the fat fraction, was analyzed by gas chromatography-mass spectrometry (GC-MS), and PPARγ and GLUT4 mRNA expressions were determined in 3T3-L1 adipocytes. The protein and fat fractions exhibited hypoglycemic effects in the acute as well as in the 30-day study. Only the fat fraction led to elevated insulin levels and reduced glycemia, as well as lower intake of water and food. In the liver, we observed recovery of close hepatic cords in the central lobule vein following treatment with the fat fraction, while in the pancreas there was an increased density and percentage of islets and number of cells per islet, suggesting cellular regeneration. The GC-MS analysis of fat revealed three fatty acids as the major components. Finally, increased expression of PPARγ and GLUT4 was observed in 3T3-L1 adipocytes, indicating an antidiabetic effect.

Perspectives on the clinical development of immunotherapy in prostate cancer / 亚洲男科学杂志(英文版)

Despite impressive survival benefits with immunotherapy in patients with various solid tumors, the full potential of these agents in prostate cancer has yet to be realized. Sipuleucel-T demonstrated a survival benefit in this population, indicating that prostate cancer is an immunoresponsive disease; however, these results have not been matched by other agents. A large trial with ipilimumab in prostate cancer failed to meet its primary objective, and small trials with PD-1/PD-L1 inhibitors did not yield a significant improvement in overall response. However, several late-stage clinical trials are underway with other vaccines in prostate cancer. Reports of clinical benefit with immunotherapies, particularly when used in combination or a select population, have provided the framework to develop sound clinical trials. Understanding immunogenic modulation, antigen spread, biomarkers, and DNA-repair defects will also help mold future strategies. Through rational patient selection and evidence-based combination approaches, patients with prostate cancer may soon derive durable survival benefits with immunotherapies.

Los reptiles en la historia de la oftalmología española: excrementos de lagarto ocelado y leucoma corneal / Reptiles in the history of Spanish ophthalmology: Ocellated lizard excrements and corneal leucoma

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Amplification of distinct α-synuclein fibril conformers through protein misfolding cyclic amplification

Amyloid fibril formation has been implicated in the pathogenesis of neurodegenerative diseases. Fibrillation generates numerous conformers. Presumably, the conformers may possess specific biological properties, thus providing a biochemical framework for strains of prions. However, the precise relationship between various fibril conformers and their pathogenic functions has not been determined because of limited accessibility to adequate amounts of fibrils from tissue samples. α-Synuclein is one such protein, and it has been implicated in Parkinson disease. Using a technique known as protein misfolding cyclic amplification, originally developed for amplifying prions, we established a procedure through which the amplification of α-synuclein fibrils is possible. With a trace amount of seeds, we succeeded in amplifying α-synuclein fibrils. The replication of the seeds was faithful in terms of conformation even after multiple rounds of cyclic amplification. Moreover, two transgenic mouse strains each representing a distinct synucleinopathy were used to investigate different conformers by using this technique. The amplified α-synuclein fibrils derived from the tissue extracts of these two strains led to the production of two different fibril conformers with distinct proteinase K digestion profiles. Together, our results demonstrated that a trace amount of α-synuclein fibrils in tissue extracts could be amplified with their conformations conserved. This procedure should be useful in amplifying α-synuclein fibrils from the brains and body fluids of patients afflicted with synucleinopathies and may serve as a potential diagnostic tool for Parkinson disease and other synucleinopathies.

Therapeutic effect of acupuncture point injection with placental extract in knee osteoarthritis / 中西医结合学报

<p><b>OBJECTIVE</b>This study evaluated the effectiveness of acupuncture point injection (API) with placental extract on pain reduction and joint function in patients with knee osteoarthritis (OA).</p><p><b>METHODS</b>Fifty-two patients with knee OA, with an average age of 64, and having a symptom duration of more than 3 months were studied in this report. Placental extract was injected weekly into acupuncture point ST35, BL23, BL24 and BL25 for 5 weeks; 8 mL of placental extract into ST35 on the affected side, and 1 mL of placental extract to BL23, BL24 and BL25 bilaterally.</p><p><b>RESULTS</b>After a five-week treatment of API with placental extract, pain was substantially decreased in patients of all Kellgren-Lawrence (KL) grades. Improvement of knee joint swelling was also apparent. Decrease of pain and joint swelling improved daily working productive time among patients of all KL grades.</p><p><b>CONCLUSION</b>Study results imply that API with placental extract is a potentially useful therapy to control pain and maintain joint functions in knee OA patients.</p>

Steroids in traditional Chinese medicine: what is the evidence?

Local healthcare providers often question the possible steroidal activity of traditional Chinese medicine (TCM) herbs or herbal products and implicate them as a cause for adrenal insufficiency or Cushing's syndrome in patients with a history of TCM intake. We conducted a comprehensive database search for evidence of potential glucocorticoid, mineralocorticoid, androgenic or oestrogenic activity of herbs or herbal products. Overall, there are not many herbs whose steroidal activity is well established; among these, most cases were based on preclinical studies. Liquorice root may cause pseudoaldosteronism through interference with the steroidogenesis pathway. Although ginseng and cordyceps have some in vitro glucocorticoid activities, the corroborating clinical data is lacking. Deer musk and deer antler contain androgenic steroids, while epimedium has oestrogenic activity. On the other hand, adulteration of herbal products with exogenous glucocorticoids is a recurrent problem encountered locally in illegal products masquerading as TCM. Healthcare providers should stay vigilant and report any suspicion to the relevant authorities for further investigations.