Magnetic targeting enhances the neuroprotective function of human mesenchymal stem cell-derived iron oxide exosomes by delivering miR-1228-5p.

BACKGROUND: Treating mitochondrial dysfunction is a promising approach for the treatment of post-stroke cognitive impairment (PSCI). HuMSC-derived exosomes (H-Ex) have shown powerful therapeutic effects in improving mitochondrial function, but the specific effects are unclear and its brain tissue targeting needs to be further optimized. RESULTS: In this study, we found that H-Ex can improve mitochondrial dysfunction of neurons and significantly enhance the cognitive behavior performance of MCAO mice in OGD/R-induced SHSY5Y cells and MCAO mouse models. Based on this, we have developed an exosome delivery system loaded with superparamagnetic iron oxide nanoparticles (Spion-Ex) that can effectively penetrate the blood-brain barrier (BBB). The research results showed that under magnetic attraction, Spion-Ex can more effectively target the brain tissue and significantly improve mitochondrial function of neurons after stroke. Meanwhile, we further confirmed that miR-1228-5p is a key factor for H-Ex to improve mitochondrial function and cognitive behavior both in vivo and in vitro. The specific mechanism is that the increase of miR-1228-5p mediated by H-Ex can inhibit the expression of TRAF6 and activate the TRAF6-NADPH oxidase 1 (NOX1) pathway, thereby exerting protective effects against oxidative damage. More importantly, we found that under magnetic attraction, Spion-Ex exhibited excellent cognitive improvement effects by delivering miR-1228-5p. CONCLUSIONS: Our research found that H-Ex has a good therapeutic effect on PSCI by increasing the expression of miR-1228-5p in PSCI, while H-Ex loaded with Spion-Ex exhibited more excellent effects on improving mitochondrial function and cognitive impairment under magnetic attraction, which can be used as a novel strategy for the treatment of PSCI.

Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression.

BACKGROUND: Neuroinflammation is an important component mechanism in the development of depression. Exosomal transfer of MDD-associated microRNAs (miRNAs) from neurons to microglia might exacerbate neuronal cell inflammatory injury. RESULTS: By sequence identification, we found significantly higher miR-9-5p expression levels in serum exosomes from MDD patients than healthy control (HC) subjects. Then, in cultured cell model, we observed that BV2 microglial cells internalized PC12 neuron cell-derived exosomes while successfully transferring miR-9-5p. MiR-9-5p promoted M1 polarization in microglia and led to over releasing of proinflammatory cytokines, such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which exacerbated neurological damage. Furthermore, we identified suppressor of cytokine signaling 2 (SOCS2) as a direct target of miR-9-5p. Overexpression of miR-9-5p suppressed SOCS2 expression and reactivated SOCS2-repressed Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways. Consistently, we confirmed that adeno-associated virus (AAV)-mediated overexpression of miR-9-5p polarized microglia toward the M1 phenotype and exacerbated depressive symptoms in chronic unpredictable mild stress (CUMS) mouse mode. CONCLUSION: MiR-9-5p was transferred from neurons to microglia in an exosomal way, leading to M1 polarization of microglia and further neuronal injury. The expression and secretion of miR-9-5p might be novel therapeutic targets for MDD.

Abnormalities in FGF family members and their roles in modulating depression-related molecules.

The role of the fibroblast growth factor (FGF) system in depression has received considerable attention in recent years. To understand the role of this system, it is important to identify the specific members of the FGF family that have been implicated and the various mechanisms that they modulated. Here, we review the role of FGFs in depression and integrate evidence from clinical and basic research. These data suggest that changes in the FGF family are involved in depression and possibly in a wider range of psychiatric disorders. We analyse the abnormalities of FGF family members in depression and their roles in modulating depression-related molecules. The role of the FGF family in depression and related disorders needs to be studied in more detail.

First report of albinism for Achalinussheni (Serpentes, Xenodermidae), with extended diagnosis of the species.

Albinism is an uncommon phenomenon and inherited condition in animals characterized by a partial or complete lack of melanin. The family Xenodermidae Gray, 1849, is a group of caenophidian snakes widely distributed in South, East, and Southeast Asia, including five recognized genera and 36 species. However, there are currently no reports of albinism in any species in Xenodermidae. Achalinussheni Ma, Xu, Qi, Wang, Tang, Huang & Jiang, 2023 was first described based on five male specimens from Loudi City and Nanyue District, Hunan Province, China. At the time, there were no descriptions on female individuals. In this study, we report in detail a collected albinistic specimen of A.sheni, which is the first discovery of wild albinism in the family Xenodermidae. We also provide photographs and descriptions of the first three female specimens of A.sheni and extend the diagnosis of this species.

A new species of the genus Hebius (Squamata, Natricidae) from Yunnan, China.

A new species of the genus Hebius Thompson, 1913 is described from Yingjiang County, Dehong Dai and Jingpo Autonomous Prefecture, Yunnan Province, China, based on molecular and morphological evidence. It can be distinguished from its congeners by the following set of characters: (1) dorsal scale rows 19-17-17, feebly keeled; (2) ventrals 146-151; (3) nasal complete, nostril in the middle of the nasal; (4) supralabials 9, the fourth to sixth in contact with the eye; (5) infralabials 10-11, the first 5 touching the first pair of chin shields; (6) preoculars 2; (7) postoculars 3; (8) temporals 3, arranged in two rows (1+2); (9) maxillary teeth 31, the last 4 slightly enlarged, without diastema; (10) tail comparatively long, TAL/TL ratio 0.334 in the male; (11) dorsolateral series of irregular orange or ochre yellow blotches, extending from the neck to the posterior part of the tail; and (12) venter pale orange, tips of ventrals with subrectangular black blotches. All Hebius specimens were strongly recovered as monophyletic, in which Hebiustaronensis (Smith, 1940) and Hebiusvenningi (Wall, 1910) were monophyletic as sister to the Yingjiang County specimens. According to the p-distance of cytochrome b, the new species differs from its congeners by 9.7-15.4%.

Xiangshao Granules Ameliorate Post-Stroke Depression by Inhibiting Activation of Microglia and IDO1 Expression in Hippocampus and Prefrontal Cortex.

OBJECTIVE: To investigate the therapeutic effect of Xiangshao Granules (XSG) on post-stroke depression (PSD) and explore the underlying mechanisms. METHODS: Forty-three C57BL/6J mice were divided into 3 groups: sham (n=15), PSD+vehicle (n=14), and PSD+XSG (n=14) groups according to a random number table. The PSD models were constructed using chronic unpredictable mild stress (CUMS) after middle cerebral artery occlusion (MCAO). The sham group only experienced the same surgical operation, but without MACO and CUMS stimulation. The XSG group received XSG (60 mg/kg per day) by gavage for 4 weeks. The mice in the sham and vehicle groups were given the same volume of 0.9% saline at the same time. The body weight and behavior tests including open field test, sucrose preference test, tail suspension test, and elevated plus-maze test, were used to validate the PSD mouse model. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining were used to evaluate the anti-inflammatory effects of XSG. The potential molecular mechanisms were explored and verified through network pharmacology analysis, Nissl staining, Western blot, ELISA, and RT-qPCR, respectively. RESULTS: The body weight and behavior tests showed that MCAO combined with CUMS successfully established the PSD models. XSG alleviated neuronal damage, reduced the expressions of pro-apoptotic proteins Caspase-3 and B-cell lymphoma-2 (BCL-2)-associated X (BAX), and increased the expression of anti-apoptotic protein BCL-2 in PSD mice (P<0.05 or P<0.01). XSG inhibited microglial activation and the expressions of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin (IL)-1 ß, and IL-6 via the toll-like receptor 4/nuclear factor kappa-B signaling pathway in PSD mice (P<0.05 or P<0.01). Furthermore, XSG decreased the expression of indoleamine 2,3-dioxygenase1 (IDO1) and increased the concentration of 5-hydroxytryptamine in PSD mice (P<0.05 or P<0.01). CONCLUSION: XSG could reverse the anxiety/depressionlike behaviors and reduce the neuronal injury in the hippocampus and prefrontal cortex of PSD mice, which may be a potential therapeutic agent for PSD.

Discovery of a new cryptic Achalinus Peters, 1869 (Serpentes, Xenodermidae) species from Hunan Province, China.

A new species, Achalinusshenisp. nov., from central Hunan Province is described, based on the results of molecular systematics and morphological characters according to five specimens. Our molecular phylogeny inferred from the mitochondrial CO1 gene fragment revealed that this new species is most closely related to A.yunkaiensis, but a considerable amount of genetic divergence exists between them (p-distance ranging from 5.8% to 6.4%) and much distinct genetic divergence exists compared with other known Achalinus species (p-distance ranging from 10.4% to 15.8%), supporting its validity. Morphologically, it can be distinguished from its congeners by: (1) dorsal scales strongly keeled, 23 rows throughout the body, the outmost row smooth and significantly enlarged; (2) tail relatively short, TaL/TL 0.183 ~ 0.224; (3) the suture between internasals subequal to the suture between prefrontals; (4) loreal one, subrectangular, LorH/LorL 0.53 ~ 0.57; (5) ventrals 161-170, anal entire, subcaudals 55-61, not paired; (6) the length of supraocular equal to or longer than the length of upper anterior temporal; and (7) vertebral line inconspicuous and subcaudal streak absent. Currently, 27 species of Achalinus are known in the world, amongst which 20 species are distributed in China. Moreover, a key to species of the genus Achalinus is provided in this study.

A new species of the genus Achalinus (Squamata: Xenodermidae) from Nanning, Guangxi, China.

We describe a new species of the genus Achalinus Peters, 1869 from Daming Mountain, Shanglin County, Nanning City, Guangxi Zhuang Autonomous Region, China, based on a single adult male specimen. It can be distinguished from all the other species in Achalinus by a combination of the following morphological characters: (1) a bright yellow collar around the neck, extending forward to the ventral of the head; (2) tail length comparatively long, TaL/Tol ratio 0.25; (3) DSR 23-23-23, moderately keeled; (4) VS 3+162; (5) SC 74, unpaired; (6) cloacal plate entire; (7) SPL 6, the fourth and fifth in contact with the eye; (8) IFL 6, the first three touching the first pair of chin shields; (9) a single loreal; (10) length of suture between internasal significantly longer than that between prefrontal, LSBI/LSBP ratio 1.34; (11) two pairs of chin shields; (12) longitudinal vertebral line absent. In addition, the uncorrected p-distances between the new species and other known congeners ranged from 6.3% to 25.4% for the cytochrome c oxidase subunit 1 (CO1). With the addition of the new species the total number of described Achalinus species is increased to 23 of which 17 are found in China.

A new species of the Genus Hebius Thompson, 1913 (Squamata: Colubridae) from Baise, Guangxi, China.

A new species of the genus Hebius Thompson, 1913 is described from Youjiang District, Baise City, Guangxi Zhuang Autonomous Region, China, based on a single adult female specimen. It can be distinguished from its congeners by the following combination of characters: (1) dorsal scale rows 19-17-17, feebly keeled except the outermost row; (2) tail length comparatively long, TAL/TL ratio 0.30 in females; (3) ventrals 160 (+ 3 preventrals); (4) subcaudals 112; (5) supralabials 9, the fourth to sixth in contact with the eye; (6) infralabials 10, the first 5 touching the first pair of chin shields; (7) preocular 1; (8) postoculars 2; (9) temporals 4, arranged in three rows (1+1+2); (10) maxillary teeth 30, the last 3 enlarged, without diastem; (11) postocular streak presence; (12) background color of dorsal brownish black, a conspicuous, uniform, continuous beige stripe extending from behind the eye to the end of the tail; (13) anterior venter creamish-yellow, gradually fades to the rear, with irregular black blotches in the middle and outer quarter of ventrals, the posterior part almost completely black. The discovery of the new species increases the number of species in the genus Hebius to 51.

A new species of the Genus Pelodiscus Fitzinger, 1835 (Testudines: Trionychidae) from Huangshan, Anhui, China.

A new species of the soft-shelled turtle genus Pelodiscus is described based on seven specimens from Huangshan, southern Anhui Province, China. The new species, Pelodiscus huangshanensis sp. nov., is distinguished from other species in the genus Pelodiscus by the following characteristics: (1) Small size (maximum carapace length of 101.16 mm and maximum body length of 190 mm); (2) keel high; (3) tiny yellowish-white spots on the throat; (4) no black pinstripes around the eyes; (5) white longitudinal bands on both sides of the neck in juveniles, absent in adults; (6) plastron yellowish-white, and only a dark patch on each side of the armpit; (7) many tubercles on the dorsal surface, but indistinct in the center; and (8) entoplastron ⌒ shaped. The phylogenetic relationships of the species in Pelodiscus were reconstructed using the sequences of cytochrome b (cyt b) and NADH dehydrogenase subunit 4 (ND4) genes. The new species formed a monophyletic clade with strong support. The uncorrected pairwise distances between the new species and other representatives of Pelodiscus ranged from 5.4% to 9.2% for cyt b and 4.1% to 7.6% for ND4. The new species brings the number of species of the genus Pelodiscus to six; five species are distributed in China, with three species endemic to China.

Fibroblast growth factor 22 is a novel modulator of depression through interleukin-1ß.

BACKGROUND AND AIMS: Emerging evidence shows that fibroblast growth factor 22 (FGF22) plays a critical role in the etiology of depression. However, the molecular mechanisms of FGF22 are not fully comprehended. Here, the effect of FGF22 in depression and its relationship with interleukin-1ß (IL-1ß) were investigated in clinical, animal, and cell experiments. METHODS: Serum from depressive patients was collected, and the levels of FGF22 and IL-1ß were analyzed by ELISA. The chronic unpredictable mild stress (CUMS) model was established, and primary hippocampal neuronal cells were cultured to examine changes in FGF22 and IL-1ß levels in rat hippocampus. RESULTS: The results revealed a negative correlation between serum FGF22 levels and serum IL-1ß levels. The expression of IL-1ß in the CUMS rat hippocampus decreased, and the apoptosis of hippocampal cells improved after the injection of lentiviral vector-mediated FGF22 (LV-FGF22). Further tests in primary hippocampal neuronal cells also showed a reduction in IL-1ß and the cell apoptosis rate after treatment with FGF22. CONCLUSION: In conclusion, the results revealed that FGF22 plays a role in alleviating depression, which may be mediated by reduced expression of IL-1ß.