Microneedles are highly sought after for medicinal and cosmetic applications. However, the current manufacturing process for microneedles remains complicated, hindering its applicability to a broader variety of applications. As diffraction lithography has been recently reported as a simple method for fabricating solid microneedles, this paper presents the experimental validation of the use of ultraviolet light diffraction to control the liquid-to-solid transition of photosensitive resin to define the microneedle shape. The shapes of the resultant microneedles were investigated utilizing the primary experimental parameters including the photopattern size, ultraviolet light intensity, and the exposure time. Our fabrication results indicated that the fabricated microneedles became taller and larger in general when the experimental parameters were increased. Additionally, our investigation revealed four unique crosslinked resin morphologies during the first growth of the microneedle: microlens, first harmonic, first bell-tip, and second harmonic shapes. Additionally, by tilting the light exposure direction, a novel inclined microneedle array was fabricated for the first time. The fabricated microneedles were characterized with skin insertion and force-displacement tests. This experimental study enables the shapes and mechanical properties of the microneedles to be predicted in advance for mass production and wide practical use for biomedical or cosmetic applications.

Multiple myeloma (MM) is a clonal B-cell disorder characterized by the proliferation of malignant plasma cells (PCs) in the bone marrow, the presence of monoclonal serum immunoglobulin, and osteolytic lesions. It is the second most common hematological malignancy and considered an incurable disease despite significant treatment improvements. MM bone disease (MMBD) is defined as the presence of one or more osteolytic bone lesions or diffused osteoporosis with compression fracture attributable to the underlying clonal PC disorder. MMBD causes severe morbidity and increases mortality. Cumulative evidence shows that the interaction of MM cells and bone microenvironment plays a significant role in MM progression, suggesting that these interactions may be good targets for therapy. MM animal models have been developed and studied in various aspects of MM tumorigenesis. In particular, MMBD has been studied in various models, and each model has unique features. As the general features of MM animal models have been reviewed elsewhere, the current review will focus on the features of MMBD animal models.

Multiple myeloma (MM) is a plasma cell malignancy that causes an accumulation of terminally differentiated monoclonal plasma cells in the bone marrow, accompanied by multiple myeloma bone disease (MMBD). MM animal models have been developed and enable to interrogate the mechanism of MM tumorigenesis. However, these models demonstrate little or no evidence of MMBD. We try to establish the MMBD model with severe bone lesions and easily accessible MM progression. 1 × 10⁶ luciferase-expressing 5TGM1 cells were injected into 8–12 week-old NOD SCID gamma mouse (NSG) and C57BL/KaLwRij mouse via the tail vein. Myeloma progression was assessed weekly via in vivo bioluminescence (BL) imaging using IVIS-200. The spine and femur/tibia were extracted and scanned by the micro-computer tomography for bone histo-morphometric analyses at the postmortem. The median survivals were 56 days in NSG while 44.5 days in C57BL/KaLwRij agreed with the BL imaging results. Histomorphic and DEXA analyses demonstrated that NSG mice have severe bone resorption that occurred at the lumbar spine but no significance at the femur compared to C57BL/KaLwRij mice. Based on these, we conclude that the systemic 5TGM1 injected NSG mouse slowly progresses myeloma and develops more severe MMBD than the C57BL/KaLwRij model.

We previously reported a substantial correlation between serum parathyroid hormone (PTH) levels and the myeloma response to proteasome inhibition that suggests a crucial role for the PTH receptor 1 system in the control of myeloma tumor growth. While investigating the role of PTH in the antimyeloma effect, we observed the recovery of serum PTH levels after thyroparathyroidectomy (TPTX). Although the presence of thymus-derived PTH has been reported previously, the existence or role of thymic PTH in the serum remains controversial. Here, TPTX was performed in 8- to 12-week-old C57BL/KaLwRij mice to delineate the potential source(s) for the recovery of serum PTH. Immediately after TPTX, the expected loss of measurable serum PTH was observed. Serum PTH levels recovered 3 to 4 weeks after TPTX. Thirteen endocrine organs from mice with recovered serum PTH were examined. The thymus from control mice expressed measurable and detectable Pth transcripts; however, the Pth transcript level was substantially elevated in tissue from TPTX mice. Western blot analysis of the thymus demonstrated a reproducible and distinct PTH band in thymus tissue that was significantly increased after TPTX. To directly confirm the identity of the distinct PTH band, immunoprecipitated proteins were isolated and subjected to tandem mass spectrometry. After fragmentation and direct peptide sequencing, PTH peptides PTH(1-13) and PTH(54-70), diagnostic for PTH, were identified. These data demonstrate that the murine thymus produces PTH and that after TPTX the thymus becomes the major source of serum PTH, compensating for the loss of the parathyroid glands and returning circulating PTH levels to normal.

Diffuse large B cell lymphoma (DLBCL) is the most diagnosed, aggressive non-Hodgkin lymphoma, with ~40% of patients experiencing refractory or relapsed disease. Given the low response rates to current therapy, alternative treatment strategies are necessary to improve patient outcomes. Here, we sought to develop an easily accessible new xenograft mouse model that better recapitulates the human disease for preclinical studies. We generated two Luciferase (Luc)-EGFP-expressing human DLBCL cell lines representing the different DLBCL cell-of-origin subtypes. After intravenous injection of these cells into humanized NSG mice, we monitored the tumor growth and evaluated the organ-specific engraftment/progression period. Our results showed that human IL6-expressing NSG (NSG-IL6) mice were highly permissive for DLBCL cell growth. In NSG-IL6 mice, systemic engraftments of both U2932 activated B cell-like- and VAL germinal B cell-like-DLBCL (engraftment rate; 75% and 82%, respectively) were detected within 2nd-week post-injection. In the organ-specific ex vivo evaluation, both U2932-Luc and VAL-Luc cells were initially engrafted and expanded in the spleen, liver, and lung and subsequently in the skeleton, ovary, and brain. Consistent with the dual BCL2/MYC translocation association with poor patient outcomes, VAL cells showed heightened proliferation in human IL6-conditioned media and caused rapid tumor expansion and early death in the engrafted mice. We concluded that the U2932 and VAL cell-derived human IL6-expressing mouse models reproduced the clinical features of an aggressive DLBCL with a highly consistent pattern of tumor development. Based on these findings, NSG mice expressing human IL6 have the potential to serve as a new tool to develop DLBCL xenograft models to overcome the limitations of standard subcutaneous DLBCL xenografts.