Simplified electrophysiological approach combining a point-of-care nerve conduction device and an electrocardiogram produces an accurate diagnosis of diabetic polyneuropathy.

AIMS/INTRODUCTION: This study aimed to investigate the diagnostic potential of two simplified tests, a point-of-care nerve conduction device (DPNCheck™) and a coefficient of variation of R-R intervals (CVR-R ), as an alternative to traditional nerve conduction studies for the diagnosis of diabetic polyneuropathy (DPN) in patients with diabetes. MATERIALS AND METHODS: Inpatients with type 1 or type 2 diabetes (n = 167) were enrolled. The study population consisted of 101 men, with a mean age of 60.8 ± 14.8 years. DPN severity was assessed using traditional nerve conduction studies, and differentiated based on Baba's classification (BC). To examine the explanatory potential of variables in DPNCheck™ and CVR-R regarding the severity of DPN according to BC, a multiple regression analysis was carried out, followed by a receiver operating characteristic analysis. RESULTS: Based on BC, 61 participants (36.5% of the total) were categorized as having DPN severity of stage 2 or more. The multiple regression analysis yielded a predictive formula with high predictive power for DPN diagnosis (estimated severity of DPN in BC = 2.258 - 0.026 × nerve conduction velocity [m/s] - 0.594 × ln[sensory nerve action potential amplitude (µV)] + 0.528In[age(years)] - 0.178 × ln[CVR-R ], r = 0.657). The area under the curve in receiver operating characteristic analysis was 0.880. Using the optimal cutoff value for DPN with severer than stage 2, the predictive formula showed good diagnostic efficacy: sensitivity of 83.6%, specificity of 79.2%, positive predictive value of 51.7% and negative predictive value of 76.1%. CONCLUSIONS: These findings suggest that DPN diagnosis using DPNCheck™ and CVR-R could improve diagnostic efficiency and accessibility for DPN assessment in patients with diabetes.

The efficacy of switching basal-bolus insulin therapy to basal insulin-supported oral therapy with a glinide and an α-glucosidase inhibitor in patients with type 2 diabetes depends on insulin secretory capacity, but not on blood glucose profiles and insulin dosages prior to the switching.

Aims: We aimed to identify patients who would benefit from basal insulin-supported oral therapy (BOT) with a glinide and an α-glucosidase inhibitor (a fixed-dose combination tablet of mitiglinide 10 mg and voglibose 0.2 mg) in Japanese type 2 diabetic patients. Methods: Patients who were hospitalized to improve hyperglycemia received basal-bolus insulin therapy. After the reduction of glucose toxicity, a 75 g oral glucose tolerance test and a glucagon test were performed. Thereafter, the basal-bolus insulin therapy was switched to BOT with mitiglinide, followed by further addition of voglibose. Interstitial glucose levels were continuously monitored throughout the study period. Diurnal glucose profile was recorded and analyzed. Patients were divided into two groups according to whether their percentage of time in range (TIR, 70-180 mg/dL) under BOT with mitiglinide/voglibose was higher than 70% or not, and the differences in clinical characteristics between the groups were analyzed. Results: Twenty patients were enrolled, and 19 of them completed the study. BOT with mitiglinide/voglibose achieved ≥ 70% of TIR in thirteen patients. The area under the curve of serum C-peptide levels during the oral glucose tolerance test was significantly higher in the patients with ≥ 70% of TIR. The daily insulin dosages and blood glucose profiles were comparable between the two groups. Conclusions: The efficacy of BOT with mitiglinide/voglibose depended on residual insulin secretory abilities. This therapy would be a useful therapeutic option for patients with type 2 diabetes.

Recent origin and diversification accompanied by repeated host shifts of thallus-mining flies (Diptera: Agromyzidae) on liverworts and hornworts.

Despite the vast diversity of phytophagous insects that feed on vascular plants (tracheophytes), insects that feed on bryophytes remain understudied. Agromyzidae, one of the most species-rich phytophagous clades in Diptera, consists mainly of leaf-mining species that feed on tracheophytes. However, a recent discovery of thallus-mining species on liverworts and hornworts within the Liriomyza group of Phytomyzinae provides an opportunity to study host shifts between tracheophytes and bryophytes. This study aimed to explore the origin and diversification of thallus-miners and estimate the pattern and timing of host shifts. Phylogenetic analysis of Phytomyzinae has revealed that the thallus-mining agromyzids formed a separate clade, which was sister to a fern pinnule-miner. The diversification of bryophyte-associated agromyzids since the Oligocene involved multiple host shifts across various bryophyte taxa. The diversification of the thallus-mining Phytoliriomyza may have occurred at the same time as the leaf-mining agromyzid flies on herbaceous plants, indicating a dynamic history of interactions between bryophytes and herbivores in angiosperms-dominated ecosystems.

Diversity and larval leaf-mining habits of Japanese jewel beetles of the tribe Tracheini (Coleoptera, Buprestidae).

From the Japanese Archipelago, 12 Habroloma and 20 Trachys species (Buprestidae: Tracheini) have been recorded. Two new Habroloma species were found, which are associated with Elaeocarpaceae and Loranthaceae, also new host plant families/orders for Tracheini. The two new species are described as Habrolomaelaeocarpusisp. nov. and Habrolomataxillusisp. nov., and the latter is the first Tracheini species shown to be associated with epiphytes. Leaf mines of 31 Tracheini species are also reported in this work, including new records of leaf mines for 16 Tracheini species. The larvae of all these recorded species are full-depth linear-blotch mesophyll miners of mature leaves and pupate within their mines. The mining habits of Habroloma species associated with Symplocos (Symplocaceae) are unique: the young larvae bore into midribs and petioles and cause leaf fall, and the larvae then mine the fallen leaves.

Erratum: Corrigendum: Kato M, Kawakita A (2023) Diversity and larval leaf-mining habits of Japanese jewel beetles of the tribe Tracheini (Coleoptera, Buprestidae). ZooKeys 1156: 133-158. doi: 10.3897/zookeys.1156.97768.

[This corrects the article DOI: 10.3897/zookeys.1156.97768.].

[Efficacy and Safety of Scalp Cooling Device RV21-01 for Suppression of Chemotherapy-Induced Alopecia in Breast Cancer Patients].

We evaluated the efficacy and safety of the RV21-01 scalp cooling device in controlling hair loss during chemotherapy in this study. Thirty-nine breast cancer patients who underwent anthracycline- and/or taxane-based chemotherapy were assigned to the scalp cooling group(27 patients)and the hair loss observation group(12 patients). The alopecia rate using the NCI alopecia toxicity criteria and the quantitative alopecia toxicity grade was 51.9%(14/27 patients)and 100%(12/12 patients)in the scalp cooling and hair loss observation groups, respectively. Regarding safety, all subjects in both the scalp cooling and hair loss observation groups experienced adverse events; only 1 subject in each group experienced a severe adverse event due to chemotherapy and majority of the subjects in both groups experienced minor adverse events. RV21-01 scalp cooling therapy was demonstrated to be effective in reducing hair loss in patients undergoing standard chemotherapy for breast cancer. In addition, the adverse events associated with the scalp cooling therapy were minor and mild, and hence, deemed acceptable.

Clinical parameters correlated with the psoas muscle index in Japanese individuals with type 2 diabetes mellitus.

Aims: Muscle atrophy is a diabetic complication, which results in a deterioration in glycemic control in type 2 diabetes mellitus (T2DM) individuals. The psoas muscle mass index (PMI) is a reliable indicator for estimating whole-body muscle mass. We aimed to examine the relationship between clinical parameters and the PMI to clarify the mechanism underlying muscle atrophy in diabetes. Methods: This retrospective, cross-sectional study examined 51 patients (31 men and 20 women) with T2DM and a mean HbA1c value of 9.9 ± 1.7%. These patients were admitted to Aichi Medical University Hospital and underwent abdominal computed tomography imaging from July 2020 to April 2021. Multiple clinical parameters were assessed with the PMI. Results: In a multiple regression analysis adjusted for age and sex, the PMI was correlated with body weight, body mass index, serum concentrations of corrected calcium, aspartate aminotransferase, alanine aminotransferase, creatine kinase, thyroid-stimulating hormone (TSH), urinary C-peptide concentrations, the free triiodothyronine/free thyroxine (FT3/FT4) ratio, and the young adult mean score at the femur neck. Receiver operating characteristic curves were created using TSH concentrations and the FT3/FT4 ratio for diagnosing a low PMI. The area under the curve was 0.593 and 0.699, respectively. The cut-off value with maximum accuracy for TSH concentrations was 1.491 µIU/mL, sensitivity was 56.1%, and specificity was 80.0%. Corresponding values for the FT3/FT4 ratio were 1.723, 78.0, and 66.7%, respectively. Conclusion: TSH concentrations and the FT3/FT4 ratio are correlated with the PMI, and their thresholds may help prevent muscle mass loss in Japanese individuals with T2DM.

MYCL-mediated reprogramming expands pancreatic insulin-producing cells.

ß cells have a limited capacity for regeneration, which predisposes towards diabetes. Here, we show that, of the MYC family members, Mycl plays a key role in proliferation of pancreatic endocrine cells. Genetic ablation of Mycl causes a reduction in the proliferation of pancreatic endocrine cells in neonatal mice. By contrast, the expression of Mycl in adult mice stimulates the proliferation of ß and α cells, and the cells persist after withdrawal of Mycl expression. A subset of the expanded α cells give rise to insulin-producing cells after this withdrawal. Transient Mycl expression in vivo is sufficient to normalize the hyperglycaemia of diabetic mice. In vitro expression of Mycl similarly provokes active replication in islet cells, even in those from aged mice. Finally, we show that MYCL stimulates the division of human adult cadaveric islet cells. Our results demonstrate that the induction of Mycl alone expands the functional ß-cell population, which may provide a regenerative strategy for ß cells.

Notes on the taxonomic status and distribution of some Cylindrotomidae (Diptera, Tipuloidea), with emphasis on Japanese species.

A morphological and molecular study of 17 Cylindrotomidae species revealed that the two subspecies of Cylindrotomadistinctissima, the Nearctic C.americana Osten Sacken, 1865, stat. reval. and the Palearctic C.distinctissima (Meigen, 1818), represent separated lineages and consequently are raised to species level. Cylindrotomajaponica Alexander, 1919, syn. nov. and C.distinctissimaalpestris Peus, 1952, syn. nov. are now known to be junior synonyms of C.distinctissima. Triogmakuwanailimbinervis Alexander, 1953, syn. nov. and T.nimbipennis Alexander, 1941, syn. nov. are now placed into synonymy under Triogmakuwanai (Alexander, 1913). The Japanese Cylindrotomidae are all redescribed and all available literature and distribution data are summarised. Supplementary descriptions and illustrations for male and female terminalia of Cylindrotomanigriventris Loew, 1849, Diogmadmitrii Paramonov, 2005, Liogmanodicornis (Osten Sacken, 1865), Phalacrocerareplicata (Linnaeus, 1758), P.tipulina Osten Sacken, 1865, and Triogmatrisulcata (Schummel, 1829) are provided. The following new distribution records are outlined; Diogmacaudata Takahashi, 1960 from Arkhangelsk Oblast, Russia; D.glabrata (Meigen, 1818) from Belarus, Latvia, and Altai Republic, Amur Oblast, Novgorod Oblast, Magadan Oblast, Samara Oblast, and Kuril Islands (Shikotan I and Paramushir I) in Russia; Liogmaserraticornis Alexander, 1919 from Khabarovsk Krai, Russia; Phalacrocerareplicata from Khabarovsk Krai, Russia; and the presence of Cylindrotomanigriventris in Altai Republic, Russia is confirmed.

Adenosine/adenosine type 1 receptor signaling pathway did not play dominant roles on the influence of sodium-glucose cotransporter 2 inhibitor in the kidney of bovine serum albumin-overloaded streptozotocin-induced diabetic mice.

AIMS/INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to display excellent renoprotective effects in diabetic kidney disease with macroalbuminuria/proteinuria. Regarding the renoprotective mechanism of SGLT2i, a sophisticated hypothesis was made by explaining the suppression of glomerular hypertension/hyperfiltration through the adenosine/adenosine type 1 receptor (A1R) signaling-mediated restoration of the tubuloglomerular feedback mechanism; however, how such A1R signaling is relevant for renoprotection by SGLT2i in diabetic kidney disease with proteinuria has not been elucidated. MATERIALS AND METHODS: Streptozotocin-induced diabetic CD-1 mice were injected with bovine serum albumin (BSA) and treated with SGLT2i in the presence/absence of A1R inhibitor administration. RESULTS: We found that the influences of SGLT2i are essentially independent of the activation of A1R signaling in the kidney of BSA-overloaded streptozotocin-induced diabetic mice. BSA-overloaded diabetic mice showed the trend of kidney damage with higher glomerular filtration rate (GFR) and the significant induction of fibrogenic genes, such as transforming growth factor-ß2 and collagen type III. SGLT2i TA-1887 suppressed diabetes-induced GFR in BSA-overloaded diabetic mice was associated with the significant suppression of transforming growth factor-ß2 and collagen type III; A1R-specific inhibitor 8-cyclopentyl-1,3-dipropylxanthine did not cancel the effects of TA-1887 on either GFR or associated gene levels. Both TA-1887 and 8-cyclopentyl-1,3-dipropylxanthine-treated BSA-overloaded diabetic mice showed suppressed glycated hemoglobin levels associated with the increased food intake. When analyzing the association among histological evaluation, GFR and potential fibrogenic gene levels, each group of mice showed distinct correlation patterns. CONCLUSIONS: A1R signaling activation was not the dominant mechanism on the influence of SGLT2i in the kidney of BSA-overloaded diabetic mice.

Kir6.2-deficient mice develop somatosensory dysfunction and axonal loss in the peripheral nerves.

Glucose-responsive ATP-sensitive potassium channels (KATP) are expressed in a variety of tissues including nervous systems. The depolarization of the membrane potential induced by glucose may lead to hyperexcitability of neurons and induce excitotoxicity. However, the roles of KATP in the peripheral nervous system (PNS) are poorly understood. Here, we determine the roles of KATP in the PNS using KATP-deficient (Kir6.2-deficient) mice. We demonstrate that neurite outgrowth of dorsal root ganglion (DRG) neurons was reduced by channel closers sulfonylureas. However, a channel opener diazoxide elongated the neurite. KATP subunits were expressed in mouse DRG, and expression of certain subunits including Kir6.2 was increased in diabetic mice. In Kir6.2-deficient mice, the current perception threshold, thermal perception threshold, and sensory nerve conduction velocity were impaired. Electron microscopy revealed a reduction of unmyelinated and small myelinated fibers in the sural nerves. In conclusion, KATP may contribute to the development of peripheral neuropathy.

Diversity underfoot of agromyzids (Agromyzidae, Diptera) mining thalli of liverworts and hornworts.

Agromyzidae is a dipteran family that has diversified as internal plant feeders. Although most agromyzid species feed on herbaceous angiosperms, only a limited number of species has been recorded as miners of bryophytes. Extensive searches and rearing of bryophytivores in the Japanese Archipelago were made, resulting in that thallus-mining agromyzids are overwhelmingly widespread and diverse on thalloid liverworts and hornworts. By examining the morphology of adult flies, it was revealed that the agromyzid fauna comprise 39 species, of which 37 species are newly described. All the species are assigned to the genus Phytoliriomyza Hendel based on some shared morphological character states as follows: costa reaching M1; orbital setulae minute and erect (rarely proclinate); male epandrium with combs of fused tubercle-like setae and/or hypertrophied arms bearing tubercle-like setae; male distiphallus comprising a pair of stout, extended tubules; female cercus with two stout, apical, trichoid sensilla. Of the 39 agromyzid species in Japan, 36 species are associated with liverworts: 5 spp. on Marchantia (Marchantiaceae), 2 spp. on Dumortiera (Dumortieraceae), 3 spp. on Plagiochasma, 1 sp. on Asterella, 6 spp. on Reboulia (Aytoniaceae), 1 sp. on Wiesnerella (Wiesnerellaceae), 15 spp. on Conocephalum (Conocephalaceae), and 3 spp. on Riccia (Ricciaceae). Three species are associated with hornworts: 1 sp. on Folioceros (Anthocerotaceae), 1 sp. on Megaceros (Dendrocerotaceae), and 1 sp. on Notothylas,Phaeoceros (Notothyladaceae), and Anthoceros (Anthocerotaceae). The results suggest that 37 of the 39 species are host-specific at least to plant genus level, and that the inter-specific differences in male genitalia and color patterns of scutum, antenna, and maxillary palpus have contributed to reproductive isolation on the bryophytes that the flies share.

Bee-Parasitic Strepsipterans (Strepsiptera: Stylopidae) Induce Their Hosts' Flower-Visiting Behavior Change.

Parasites sometimes manipulate their host's behavior to increase their own fitness by enhancing the likelihood that their offspring will reach their hosts. Bees are often parasitized by immobile adult female strepsipterans which seem to modify bees' behavior to facilitate the release of mobile first-instar larvae onto flowers. To better understand how the parasite may modify the host's behavior, we compared the foraging behavior of the sweat bee Lasioglossum apristum (Vachal, 1903) (Hymenoptera: Halictidae) between bees parasitized and unparasitized by the strepsipteran Halictoxenos borealis Kifune, 1982 (Strepsiptera: Stylopidae). Both parasitized and unparasitized bees frequently visited Hydrangea serrata (Thunb.) (Cornales: Hydrangeaceae) inflorescences, which are polleniferous but nectarless. On H. serrata inflorescences, unparasitized bees collected pollen from the anthers, but parasitized bees did not collect or eat pollen. Instead, they displayed a peculiar behavior, bending their abdomens downward and pressing them against the flower. This peculiar behavior, which was observed only in bees parasitized by a female strepsipteran in the larvae-releasing stage, may promote the release of mobile first-instar larvae onto flowers. Our observations suggest that the altered flower-visiting behavior of parasitized bees may benefit the parasite. Moreover, it suggests that strepsipteran parasites may modify their host's behavior only when the larvae reach a certain life stage.

Elucidation and control of low and high active populations of alkaline phosphatase molecules for quantitative digital bioassay.

Alkaline phosphatase (ALP), a homo-dimeric enzyme has been widely used in various bioassays as disease markers and enzyme probes. Recent advancements of digital bioassay revolutionized ALP-based diagnostic assays as seen in rapid growth of digital ELISA and the emerging multiplex profiling of single-molecule ALP isomers. However, the intrinsic heterogeneity found among ALP molecules hampers the ALP-based quantitative digital bioassays. This study aims quantitative analysis of single-molecule activities of ALP from Escherichia coli and reveals the static heterogeneity in catalytic activity of ALP with two distinct populations: half-active and fully-active portions. Digital assays with serial buffer exchange uncovered single-molecule Michaelis-Menten kinetics of ALP; half-active molecules have halved values of the catalytic turnover rate, kcat , and the rate constant of productive binding, kon , of the fully active molecules. These findings suggest that half-active ALP molecules are heterogenic dimers composed of inactive and active monomer units, while fully active ALP molecules comprise two active units. Static heterogeneity was also observed for ALP with other origins: calf intestine or shrimp, showing how the findings can be generalized across species. Cell-free expression of ALP with disulfide bond enhancer and spiked zinc ion resulted in homogenous population of ALP of full activity, implying that inactive monomer units of ALP are deficient in correct disulfide bond formation and zinc ion coordination. These findings provide basis for further study on molecular mechanism and biogenesis of ALP, and also offer the way to prepare homogenous and active populations of ALP for highly quantitative and sensitive bioassays with ALP.

Snails riding mantis shrimps: Ectoparasites evolved from ancestors living as commensals on the host's burrow wall.

The molluscan class Gastropoda includes over 5,000 parasitic species whose evolutionary origins remain poorly understood. Marine snails of the genus Caledoniella (Caledoniellidae) are obligate parasites that live on the abdominal surface of the gonodactylid mantis shrimps. They have highly modified morphological characteristics specialized to the ectoparasitic lifestyle that make it difficult to infer their close relatives, thereby posing a question about their current systematic position in the superfamily Vanikoroidea. In the present study, we performed molecular phylogenetic analyses using three nuclear and three mitochondrial gene sequences to unveil the phylogenetic position of these enigmatic snails. The resulting trees recovered Caledoniella in the superfamily Truncatelloidea and within a subclade of commensal species that live on the burrow wall of marine benthic invertebrates. More specifically, Caledoniella formed the sister clade to a commensal snail species living in mantis-shrimp burrows and they collectively were sister to Sigaretornus planus (formerly in the family Tornidae or Vitrinellidae), a commensal living in echiuran burrows. This topology suggests that the species of Caledoniella achieved their ectoparasitic mode of life through the following evolutionary pathway: (1) invasion into the burrows of benthic invertebrates, (2) specialization to mantis shrimps, and (3) colonization of the host body surface from the host burrow wall with the evolution of the parasitic nature. The final step is likely to have been accompanied by the acquisition of a sucker on the metapodium, the loss of the radula and operculum, and the formation of monogamous pair bonds. The present molecular phylogeny also suggested parallel evolution of planispiral shells in a subclade of Truncatelloidea and enabled us to newly redefine the families Caledoniellidae, Elachisinidae, Teinostomatidae, Tornidae and Vitrinellidae.

The effect of denosumab in breast cancer patients receiving adjuvant aromatase inhibitors: 36-month results.

INTRODUCTION: Aromatase inhibitor (AI)-associated bone loss increases the risk of bone fracture and reduces patients' quality of life, making it a critical issue worldwide. We conducted a prospective non-randomized clinical trial (UMIN-CTR, UMIN 000016173) to assess the effect of denosumab on bone loss in patients treated with adjuvant AI and have previously reported the results at 12 and 24 months. This study aimed to present the results at 36 months of treatment with denosumab for osteopenia in breast cancer patients who were undergoing treatment with adjuvant AI; 36 months is the longest denosumab treatment period reported so far. MATERIALS AND METHODS: Patients received 60-mg denosumab subcutaneously every 6 months. Daily supplements containing 500-mg elemental calcium and at least 400 international units of vitamin D were highly recommended throughout the study period. The levels of bone mineral density (BMD) and bone turnover markers, serum tartrate-resistant acid phosphatase isoform 5b, and bone alkaline phosphatase were determined at baseline and 6, 12, 18, 24, and 36 months. RESULTS: At 36 months, the bone mineral density of the lumbar spine, right femoral neck, and left femoral neck were found to increase by 8.8% (95% confidence interval CI 7.6-10.1), 4.3% (95% CI 3.0-5.5), and 3.1% (95% CI 2.1-4.1), respectively. No non-traumatic clinical fractures occurred in patients receiving AI and denosumab. CONCLUSION: Twice-yearly administration of denosumab to the breast cancer patients treated with adjuvant AI, regardless of the skeletal site, resulted in consistent increases in BMD without severe adverse events at 36 months.

Alterations of retinal thickness measured by optical coherence tomography correlate with neurophysiological measures in diabetic polyneuropathy.

AIMS/INTRODUCTION: Diabetic polyneuropathy (DPN) and diabetic retinopathy (DR) are traditionally regarded as microvascular complications. However, these complications may share similar neurodegenerative pathologies. Here we evaluate the correlations in the severity of DPN and changes in the thickness of neuroretinal layers to elucidate whether these complications exist at similar stages of progression. MATERIALS AND METHODS: A total of 43 patients with type 2 diabetes underwent a nerve conduction study (NCS), a macular optical coherence tomography, and a carotid artery ultrasound scan. Diabetic polyneuropathy was classified according to Baba's classification using NCS. The retina was automatically segmented into four layers; ganglion cell complex (GCC), inner nuclear layer/outer plexiform layer (INL/OPL), outer nuclear layer/photoreceptor inner and outer segments, and retinal pigment epithelium (RPE). The thickness of each retinal layer was separately analyzed for the fovea and the parafovea. RESULTS: Fourteen patients were classified as having moderate to severe diabetic polyneuropathy. The thicknesses of the foveal and parafoveal INL/OPL increased in patients with diabetic polyneuropathy compared with patients without. The thickness of the parafoveal retinal pigment epithelium decreased in patients with diabetic polyneuropathy. The thinning of parafoveal ganglion cell complex and foveal and parafoveal retinal pigment epithelium were positively correlated with deterioration of nerve functions in the nerve conduction study, but the thickening of INL/OPL was positively correlated with the nerve function deterioration. The thinning of parafoveal ganglion cell complex and foveal retinal pigment epithelium were positively correlated with the thickening of the carotid intima-media. CONCLUSIONS: Depending on the progression of diabetic polyneuropathy, the ganglion cell complex and retinal pigment epithelium became thinner and the INL/OPL became thicker. These retinal changes might be noteworthy for pathological investigations and for the assessment of diabetic polyneuropathy and diabetic retinopathy.

Secreted Factors from Stem Cells of Human Exfoliated Deciduous Teeth Directly Activate Endothelial Cells to Promote All Processes of Angiogenesis.

Diabetes is a major risk factor for atherosclerosis and ischemic vascular diseases. Recently, regenerative medicine is expected to be a novel therapy for ischemic diseases. Our previous studies have reported that transplantation of stem cells promoted therapeutic angiogenesis for diabetic neuropathy and ischemic vascular disease in a paracrine manner, but the precise mechanism is unclear. Therefore, we examined whether secreted factors from stem cells had direct beneficial effects on endothelial cells to promote angiogenesis. The soluble factors were collected as conditioned medium (CM) 48 h after culturing stem cells from human exfoliated deciduous teeth (SHED) in serum-free DMEM. SHED-CM significantly increased cell viability of human umbilical vein endothelial cells (HUVECs) in MTT assays and accelerated HUVECs migration in wound healing and Boyden chamber assays. In a Matrigel plug assay of mice, the migrated number of primary endothelial cells was markedly increased in the plug containing SHED-CM or SHED suspension. SHED-CM induced complex tubular structures of HUVECs in a tube formation assay. Furthermore, SHED-CM significantly increased neovascularization from the primary rat aorta, indicating that SHED-CM stimulated primary endothelial cells to promote comprehensive angiogenesis processes. The angiogenic effects of SHED-CM were the same or greater than the effective concentration of VEGF. In conclusion, SHED-CM directly stimulates vascular endothelial cells to promote angiogenesis and is promising for future clinical application.

Deficiency of glucagon gene-derived peptides induces peripheral polyneuropathy in mice.

Although diabetic polyneuropathy (DPN) is the commonest diabetic complication, its pathology remains to be clarified. As previous papers have suggested the neuroprotective effects of glucagon-like peptide-1 in DPN, the current study investigated the physiological indispensability of glucagon gene-derived peptides (GCGDPs) including glucagon-like peptide-1 in the peripheral nervous system (PNS). Neurological functions and neuropathological changes of GCGDP deficient (gcg-/-) mice were examined. The gcg-/- mice showed tactile allodynia and thermal hyperalgesia at 12-18 weeks old, followed by tactile and thermal hypoalgesia at 36 weeks old. Nerve conduction studies revealed a decrease in sensory nerve conduction velocity at 36 weeks old. Pathological findings showed a decrease in intraepidermal nerve fiber densities. Electron microscopy revealed a decrease in circularity and an increase in g-ratio of myelinated fibers and a decrease of unmyelinated fibers in the sural nerves of the gcg-/- mice. Effects of glucagon on neurite outgrowth were examined using an ex vivo culture of dorsal root ganglia. A supraphysiological concentration of glucagon promoted neurite outgrowth. In conclusion, the mice with deficiency of GCGDPs developed peripheral neuropathy with age. Furthermore, glucagon might have neuroprotective effects on the PNS of mice. GCGDPs might be involved in the pathology of DPN.

Shift of Feeding Mode in an Epizoic Stalked Barnacle Inducing Gall Formation of Host Sea Urchin.

Among diverse stalked barnacles, Rugilepas pearsei (Thoracica: Cirripedia: Arthropoda) is a rare unique species that is associated with echinoids and has highly atrophied cirri. We rediscovered the barnacle for the first time from description and verified that the barnacles live obligately in half-open galls formed on the test of the sea urchin Echinothrix diadema (Diadematidae: Echinodermata). A molecular phylogenetic analysis demonstrated that the obligate association with echinoids derived from epizoic life on crustaceans. A stable isotope analysis suggests that the barnacle feeds on particulate organic matter (POM) without parasitizing the host echinoids. These findings suggest that the host shift caused losses of plates and feather-like cirri, changes in the attachment device from cementation to anchoring, and a shift in feeding mode from filter feeding to POM collection. The barnacle's epizoic, superficially sub-endozoic, communal life in stout but narrow galls causes repetitive reproduction at the cost of reduced growth.