Intracellular Survival and Pathogenicity Modulation of Salmonella Lon, CpxR, and RfaL Mutants Used as Live Bacterial Vectors under Abiotic Stress, Unveiling the Link between Stress Response and Virulence in Epithelial Cells.

In the current study, two Salmonella Typhimurium strains, JOL 912 and JOL 1800, were engineered from the wild-type JOL 401 strain through in-frame deletions of the lon and cpxR genes, with JOL 1800 also lacking rfaL. These deletions significantly attenuated the strains, impairing their intracellular survival and creating unique immunological profiles. This study investigates the response of these strains to various abiotic stress conditions commonly experienced in vivo, including temperature, acidity, osmotic, and oxidative stress. Notably, cold stress induced a non-significant trend towards increased invasion by Salmonella compared to other stressors. Despite the observed attenuation, no significant alterations in entry mechanisms (trigger vs. zipper) were noted between these strains, although variations were evident depending on the host cell type. Both strains effectively localized within the cytoplasm, demonstrating their ability to invade and interact with the intracellular environment. Immunologically, JOL 912 elicited a robust response, marked by substantial activation of nuclear factor kappa B (NF-kB), and chemokines, interleukin 8 (CXCL 8) and interleukin 10 (CXCL 10), comparable to the wild-type JOL 401 (over a fourfold increase compared to JOL 1800). In contrast, JOL 1800 exhibited a minimal immune response. Additionally, these attenuations influenced the expression of cyclins D1 and B1 and caspases 3 and 7, indicating cell cycle arrest at the G2/M phase and promotion of the G0/G1 to S phase transition, alongside apoptosis in infected cells. These findings provide valuable insights into the mechanisms governing the association, internalization, and survival of Salmonella mutants, enhancing our understanding of their regulatory effects on host cell physiology.

Morphology of the aortic arch branching pattern in raccoon dogs (Nyctereutes procyonoides, Gray, 1834).

BACKGROUND: Aortic arch (AA) branching patterns vary among different mammalian species. Most previous studies have focused on dogs, whereas those on raccoon dogs remain unexplored. OBJECTIVES: The objective of this study was to describe the AA branching pattern in raccoon dogs and compare their morphological features with those of other carnivores. METHODS: We prepared silicone cast specimens from a total of 36 raccoon dog carcasses via retrograde injection through the abdominal aorta. The brachiocephalic trunk (BCT) branching patterns were classified based on the relationship between the left and right common carotid arteries. The subclavian artery (SB) branching pattern was examined based on the order of the four major branches: the vertebral artery (VT), costocervical trunk (CCT), superficial cervical artery (SC), and internal thoracic artery (IT). RESULTS: In most cases (88.6%), the BCT branched off from the left common carotid artery and terminated in the right common carotid and right subclavian arteries. In the remaining cases (11.4%), the BCT formed a bicarotid trunk. The SB exhibited various branching patterns, with 26 observed types. Based on the branching order of the four major branches, we identified the main branching pattern, in which the VT branched first (98.6%), the CCT branched second (81.9%), the SC branched third (62.5%), and the IT branched fourth (52.8%). CONCLUSIONS: The AA branching pattern in raccoon dogs exhibited various branching patterns with both similarities and differences compared to other carnivores.

Veronica persica ameliorates acetaminophen-induced murine hepatotoxicity via attenuating oxidative stress and inflammation.

Excess acetaminophen (APAP) commonly causes severe acute liver injury (ALI), characterized by oxidative stress, pro-inflammatory responses, and hepatocyte damage. Veronica persica (VP) is a traditional medicine with antioxidant and anti-inflammatory properties. There is a paucity of information on its medicinal value, especially its potential mechanisms for alleviating ALI. This study aimed to clarify the ameliorative effects and intracellular mechanisms of VP on APAP-induced ALI via attenuating oxidative stress and inflammation. Mice were given VP for 7 days before exposure to APAP (300 mg/kg). The HPLC and radical scavenging assay found that VP contains 12 phenolic acids and 6 flavonoids, as well as show robust antioxidant capacity. In the APAP-induced ALI model, pre-treatment with VP significantly reduces APAP-induced hepatotoxicity by observing improved hepatocyte pathological injury and further confirmed by serum biochemical indicator. Also, the reduction of TUNEL-positive regions and the regulation of Bcl-2-associated X protein indicated that VP attenuates hepatocytotoxicity. Moreover, VP pre-intervention inhibits the formation of liver pro-inflammatory cytokines, the expression of inflammatory response genes, and increases in myeloperoxidase (MPO) in APAP-exposed mice. The elevated reduced glutathione (GSH) levels and decreased oxidative stress markers indicate that VP reduces APAP-promoted oxidative stress. Further study revealed that VP inhibited the phosphorylation of NF-κB/STAT3 cascade, blocked ERK and JNK phosphorylation, and activated AMP-activated protein kinase (AMPK). To sum up, this study demonstrated that VP exists hepatoprotective abilities on APAP-induced ALI, primarily by suppressing the phosphorylation of NF-κB/STAT3 cascade and ERK-JNK and inducing AMPK activation to alleviate oxidative stress and inflammation.

Morphological and morphometric study of the scapulae of Korean wild deer.

Korean water deer (Hydropotes inermis argyropus; Heude, 1884) and Siberian roe deer (Capreolus pygargus; Pallas, 1771) are Korean wild deer classified in the tribe Capreolini. C. pygargus in Korea were previously considered a single species; however, it was recently suggested that roe deer living on Jeju Island (Jeju roe deer; Capreolus pygargus jejuensis) is a distinct subspecies from roe deer living on the Korean peninsula (mainland roe deer; Capreolus pygargus tianschanicus) based on several studies demonstrating genetic and morphological features. In this study, we suggests that the scapular morphology and osteometric data can be used for interspecies discrmination between Korean wild deer. To compare the morphological characteristics of scapula among the three groups of deer, we analyzed the features and nine osteomorphological measurements of 31 H. i. argyropus (14 males and 17 females), 18 C. p. jejuensis (4 males and 14 females), and 23 C. p. tianschanicus (16 females and 7 males). The estimated ages of the deer were over 32-35 months. Data were analyzed by one-way repeated measures analysis of variance with post hoc Duncan test and discriminant functional analysis (DFA). H. i. argyropus and C. p. tianschanicus had the smallest and largest scapulae, respectively. The scapulae of the three Korean wild deer had a similar triangular shape, which was obscured by the tuber of the scapular spine, pointed acromion, broad infraspinous fossa, narrow supraspinous fossa, and partial ossification of scapular cartilage in older deer. H. i. argyropus had certain distinctive features, including a caudally pointed acromion, a notch between the supraglenoid tubercle and glenoid cavity (NBSG), a glenoid notch, and no sexual dimorphism, except for the longest dorsal length (Ld) and the scapular index (SI). C. p. jejuensis had a larger scapular index (SI) (61.74 ± 0.74%), compared with the SIs of H. i. argyropus and C. p. tianschanicus. The unique features of the scapula in C. p. jejuensis include its S-shaped cranial border. The C. p. jejuensis had a cranially pointed acromion, less frequent presence of glenoid notch and NBSG, short length of supraglenoid tubercle, and no sexual dimorphism. The C. p. tianschanicus had elevated cranial margin of the glenoid cavity, and frequent presence of glenoid notch and NBSG, similar to the H. i. argyropus. Similar to C. p. jejuensis, C. p. tianschanicus had a cranially pointed acromion. However, sexual dimorphism was observed in C. p. tianschanicus. DFA using osteometric data showed 97.22% of specimens were classified correctly into their species, meaning the osteometric parameters can be used for interspecies discrimination of Korean wild deer. Our findings indicate that the scapular morphologies of the three Korean wild deer have certain similarities and differences, suggesting that C. p. jejuensis are distinct from C. p. tianschanicus.

Olanzapine Ameliorates Ischemic Stroke-like Pathology in Gerbils and H2O2-Induced Neurotoxicity in SH-SY5Y Cells via Inhibiting the MAPK Signaling Pathway.

Olanzapine (OLNZ) is used to treat psychotic disorders. To look into the neurological basis of this phenomenon, we investigated the neuroprotective effects of OLNZ in gerbils and SH-SY5Y cells. Gerbils were subjected to transient global cerebral ischemia (TGCI) by blocking both common carotid arteries, and OLNZ (10 mg/kg) was injected intraperitoneally. Hydrogen peroxide (H2O2) was used to induce oxidative-stress-mediated damage in the SH-SY5Y cells. The results indicated that OLNZ administration markedly reduced neuron damage and glial cell triggering within CA1 zone of the hippocampus. We used RNA sequencing to assess the numbers of up-and downregulated genes involved in TGCI. We found that OLNZ treatment downregulated the expression of complement-component-related genes and the expression of mitogen-activated protein kinases (MAPKs) in the hippocampus. In cells, OLNZ co-treatment significantly improved cell viability and reduced lactate dehydrogenase (LDH), and reactive oxygen species (ROS) generation. Expression of antioxidant superoxide dismutase-1,2 enzymes (SOD-1, SOD-2) was also intensely upregulated by OLNZ, while the expression of MAPKs and NF-κB were reduced. Co-incubation with OLNZ also regulated apoptosis-related proteins Bax/Bcl-2 expression. Finally, the results demonstrated that treatment with OLNZ showed neuroprotective effects and that the MAPK pathway could involve in the protective effects.

Fermented Mentha arvensis administration provides neuroprotection against transient global cerebral ischemia in gerbils and SH-SY5Y cells via downregulation of the MAPK signaling pathway.

BACKGROUND: Globally, ischemic stroke is a major health threat to humans that causes lifelong disability and death. Mentha arvensis (MA) has been used in traditional medicine to alleviate oxidative stress and inflammation-related disorders. In the present study, the neuroprotective properties of fermented MA (FMA) extract were investigated in the gerbil and SH-SY5Y cells. model of transient global cerebral ischemia. METHODS: Bilateral common carotid artery occlusion-induced transient global cerebral ischemia in gerbil and hydrogen peroxide (H2O2)-mediated neurotoxic effects in human neuroblastoma cells (SH-SY5Y) were investigated. FMA (400 mg/kg) was orally administered for 7 days before induction of ischemic stroke. To evaluate the neuroprotective activity of FMA, we implemented various assays such as cell viability assay (MTT), lactate dehydrogenase (LDH) assay, histopathology, immunohistochemistry (IHC), histofluorescence, and western blot. RESULTS: FMA pretreatment effectively decreased transient ischemia (TI) induced neuronal cell death as well as activation of microglia and astrocytes in the hippocampal region. The protective effects of FMA extract against H2O2-induced cytotoxicity of SH-SY5Y cells were observed by MTT and LDH assay. However, FMA pretreatment significantly increased the expression of the antioxidant marker proteins such as superoxide dismutase-1 (SOD-1) and superoxide dismutase-2 (SOD-2) in the hippocampus and SH-SY5Y cells. Furthermore, the activation of mitogen-activated protein kinase (MAPK) further activated a cascade of outcomes such as neuroinflammation and apoptosis. FMA pretreatment notably decreased TI and H2O2 induced activation of MAPK (c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), and p38) proteins in hippocampus and SH-SY5Y cells respectively. Besides, pretreatment with FMA markedly reduced H2O2 mediated Bax/Bcl2 expression in SH-SY5Y cells. CONCLUSION: Thus, these results demonstrated that neuroprotective activities of FMA might contribute to regulating the MAPK signaling pathway.

Effect of therapeutic hypothermia against renal injury in a rat model of asphyxial cardiac arrest: Α focus on the survival rate, pathophysiology and antioxidant enzymes.

Although multi­organ dysfunction is associated with the survival rate following cardiac arrest (CA), the majority of studies to date have focused on hearts and brains, and few studies have considered renal failure. The objective of the present study, therefore, was to examine the effects of therapeutic hypothermia on the survival rate, pathophysiology and antioxidant enzymes in rat kidneys following asphyxial CA. Rats were sacrificed one day following CA. The survival rate, which was estimated using Kaplan­Meier analysis, was 42.9% one day following CA. However, hypothermia, which was induced following CA, significantly increased the survival rate (71.4%). In normothermia rats with CA, the serum blood urea nitrogen level was significantly increased one day post­CA. In addition, the serum creatinine level was significantly increased one day post­CA. However, in CA rats exposed to hypothermia, the levels of urea nitrogen and creatinine significantly decreased following CA. Histochemical staining revealed a significant temporal increase in renal injury after the normothermia group was subjected to CA. However, renal injury was significantly decreased in the hypothermia group. Immunohistochemical analysis of the kidney revealed a significant decrease in antioxidant enzymes (copper­zinc superoxide dismutase, manganese superoxide dismutase, glutathione peroxidase and catalase) with time in the normothermia group. However, in the hypothermia group, these enzymes were significantly elevated following CA. Collectively, the results revealed that renal dysfunction following asphyxial CA was strongly associated with the early survival rate and therapeutic hypothermia reduced renal injury via effective antioxidant mechanisms.

Therapeutic hypothermia effect on asphyxial cardiac arrest-induced renal ischemia/reperfusion injury via change of Nrf2/HO-1 levels.

The present study aimed to investigate the renoprotective effect of therapeutic hypothermia (TH) on renal ischemia-reperfusion injury (RI/RI) induced by asphyxial cardiac arrest (CA) in rats. A total of 48 male rats were randomly divided into five groups: i) Sham (n=6); ii) Normothermia + CA (Normo.) (n=14); iii) Normo. and 2 h of TH after return of spontaneous circulation (ROSC) (n=12); iv) Normo. and 4 h of TH after ROSC (n=9); and v) Normo. and 6 h of TH after ROSC (n=7). All rats except the Sham group underwent asphyxia CA and were sacrificed 1 day after ROSC. The survival rate increased from 42.8% in the Normo. group to 50, 66.6 and 85.7% in the groups with 2, 4 and 6 h of TH after CA, respectively. TH attenuated the histopathological changes of the renal tissues following ROSC and the levels of blood urea nitrogen, serum creatinine and malondialdehyde in renal tissues. On immunohistochemistry, the relative optical density of nuclear erythroid-related factor-2 (Nrf2) and heme oxygenase (HO-1) expression in renal tissues increased in the Normo. group compared with that in the Sham group and exhibited further significant increases at 6 h of TH after ROSC. In conclusion, TH attenuated renal injury and increased the expression of Nrf2 and HO-1 in a TH treatment time-dependent manner.

Ethanol Extract of Maclura tricuspidata Fruit Protects SH-SY5Y Neuroblastoma Cells against H2O2-Induced Oxidative Damage via Inhibiting MAPK and NF-κB Signaling.

Free radical generation and oxidative stress push forward an immense influence on the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Maclura tricuspidata fruit (MT) contains many biologically active substances, including compounds with antioxidant properties. The current study aimed to investigate the neuroprotective effects of MT fruit on hydrogen peroxide (H2O2)-induced neurotoxicity in SH-SY5Y cells. SH-SY5Y cells were pretreated with MT, and cell damage was induced by H2O2. First, the chemical composition and free radical scavenging properties of MT were analyzed. MT attenuated oxidative stress-induced damage in cells based on the assessment of cell viability. The H2O2-induced toxicity caused by ROS production and lactate dehydrogenase (LDH) release was ameliorated by MT pretreatment. MT also promoted an increase in the expression of genes encoding the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). MT pretreatment was associated with an increase in the expression of neuronal genes downregulated by H2O2. Mechanistically, MT dramatically suppressed H2O2-induced Bcl-2 downregulation, Bax upregulation, apoptotic factor caspase-3 activation, Mitogen-activated protein kinase (MAPK) (JNK, ERK, and p38), and Nuclear factor-κB (NF-κB) activation, thereby preventing H2O2-induced neurotoxicity. These results indicate that MT has protective effects against H2O2-induced oxidative damage in SH-SY5Y cells and can be used to prevent and protect against neurodegeneration.

Changes of renal histopathology and the role of Nrf2/HO-1 in asphyxial cardiac arrest model in rats.

PURPOSE: To investigate the role of Nrf2/HO-1 in renal histopathological ailments time-dependently in asphyxial cardiac arrest (CA) rat model. METHODS: Eighty-eight Sprague Dawley male rats were divided into five groups of eight rats each. Asphyxial CA was induced in all the experimental rats except for the sham group. The rats were sacrificed at 6 hours, 12 hours, one day and two days post-CA. Serum blood urea nitrogen (BUN), creatinine (Crtn) and malondialdehyde from the renal tissues were evaluated. Hematoxylin and eosin and periodic acid-Schiff staining were done to evaluate the renal histopathological changes in the renal cortex. Furthermore, Nrf2/HO-1 immunohistochemistry (ihc) and western blot analysis were performed after CA. RESULTS: The survival rate of rats decreased in a time-dependent manner: 66.6% at 6 hours, 50% at 12 hours, 38.1% in one day, and 25.8% in two days. BUN and serum Crtn markedly increased in CA-operated groups. Histopathological ailments of the renal cortical tissues increased significantly from 6 hours until two days post-CA. Furthermore, Nrf2/HO-1 expression level significantly increased at 6 hours, 12 hours, and one day. CONCLUSIONS: The survival rate decreased time-dependently, and Nrf/HO-1 expression increased from 6 hours with the peak times at 12 hours, and one day post-CA.

Camellia japonica diminishes acetaminophen-induced acute liver failure by attenuating oxidative stress in mice.

This experiment was to explore the possible defensive properties and potential molecular mechanisms of Camellia japonica (CJ) against APAP-stimulated acute liver failure (ALF) in mice. In this study, we investigated the effects of CJ on APAP-induced hepatotoxicity. Mice were orally treated with CJ before or after challenge with APAP. Both pretreatment and post-treatment with CJ attenuated APAP-induced hepatotoxicity, as confirmed by significantly reduced serum toxicity biomarkers and improved hepatic pathological damage. Pretreatment with CJ drastically decreased the rise of hepatic inflammatory cytokines levels and weakened neutrophil infiltration. Furthermore, pretreatment with CJ dramatically decreased the levels of hepatic oxidative stress markers such as hepatic malondialdehyde (MDA) and 4-Hydroxynonenal (4-HNE) expression and rescued the reduced hepatic level of GSH caused by APAP overdose. Additionally, CJ pretreatment markedly attenuated cyclooxygenase-2 (COX-2) activation, transcription factor nuclear factor-kappa B (NF-κB) phosphorylation, c-Jun-N-terminal kinase (JNK) phosphorylation, and activated AMP-activated protein kinase (AMPK) signaling pathway in the liver. The present study thus reveals that CJ attenuated APAP-induced ALF by inhibiting COX-2 activation, NF-κB, and JNK phosphorylation and activating the AMPK signaling pathway.

Changes of renal histopathology and the role of Nrf2/HO-1 in asphyxial cardiac arrest model in rats

ABSTRACT Purpose To investigate the role of Nrf2/HO-1 in renal histopathological ailments time-dependently in asphyxial cardiac arrest (CA) rat model. Methods Eighty-eight Sprague Dawley male rats were divided into five groups of eight rats each. Asphyxial CA was induced in all the experimental rats except for the sham group. The rats were sacrificed at 6 hours, 12 hours, one day and two days post-CA. Serum blood urea nitrogen (BUN), creatinine (Crtn) and malondialdehyde from the renal tissues were evaluated. Hematoxylin and eosin and periodic acid-Schiff staining were done to evaluate the renal histopathological changes in the renal cortex. Furthermore, Nrf2/HO-1 immunohistochemistry (ihc) and western blot analysis were performed after CA. Results The survival rate of rats decreased in a time-dependent manner: 66.6% at 6 hours, 50% at 12 hours, 38.1% in one day, and 25.8% in two days. BUN and serum Crtn markedly increased in CA-operated groups. Histopathological ailments of the renal cortical tissues increased significantly from 6 hours until two days post-CA. Furthermore, Nrf2/HO-1 expression level significantly increased at 6 hours, 12 hours, and one day. Conclusions The survival rate decreased time-dependently, and Nrf/HO-1 expression increased from 6 hours with the peak times at 12 hours, and one day post-CA.

Protective effects of therapeutic hypothermia on renal injury in an asphyxial cardiac arrest rat model.

Cardiac arrest (CA) is a leading cause of mortality worldwide. Most of post-resuscitation related deaths are due to post-cardiac arrest syndrome (PCAS). After cardiopulmonary resuscitation (CPR), return of spontaneous circulation (ROSC) leads to renal ischemia-reperfusion injury, also known as PCAS. Many studies have focused on brain and heart injuries after ROSC, but renal failure has largely been ignored. Therefore, we investigated the protective effects of therapeutic hypothermia (TH) on asphyxial CA-induced renal injury in rats. Thirty rats were randomly divided into five groups: 1) the control group (sham); 2) the normothermic CA (nor.); 3) a normothermic CA group that received TH immediately within 2 h after CPR (Hypo. 2 hrs); 4) a normothermic CA group that received TH within 4 h after CPR (Hypo. 4 hrs); and 5) a normothermia CA group that received TH within 6 h after CPR (Hypo. 6 h). One day after CPR, all rats were sacrificed. Compared with the normothermic CA group, the TH groups demonstrated significantly increased survival rate (P < 0.05); decreased serum blood urea nitrogen, creatinine, and lactate dehydrogenase levels; and lower histological damage degree and malondialdehyde concentration in their renal tissue. Terminal deoxynucleotidyl transferase dUTP nick end labeling stain revealed that the number of apoptotic cells significantly decreased after 4 h and 6 h of TH compared to the results seen in the normothermic CA group. Moreover, TH downregulated the expression of cyclooxygenase-2 in the renal cortex compared to the normothermic CA group one day after CPR. These results suggest that TH exerts anti-apoptotic, anti-inflammatory, and anti-oxidative effects immediately after ROSC that protect against renal injury.

PR domaincontaining protein 12 (prdm12) is a downstream target of the transcription factor zic1 during cellular differentiation in the central nervous system: PR domain containing protein is the right form.

Transcription factor zic1 is an important regulator of neural plate patterning, formation of neural crest and cerebellar development, where its main function is neuronal cell differentiation. Among the genes identified, PR domain-containing 12 (prdm12) is a member of the prdm family and is expressed in the placode domain in the neurula stage. prdm12 is distinctly expressed in the dorsal part of the midbrain, trigeminal ganglion, and the motor neuron in the spinal cord. prdm12 knockdown results in the ventralization of the neural tube. zic1 knockdown results in the reduction of prdm12 expression in the midbrain, motor neuron and trigeminal ganglion, and overexpression of zic1 results in the expansion of prdm12 expression in the midbrain. zic1-activated wnt signaling is also a regulator of prdm12 expression in the midbrain. We propose that prdm12 is the downstream of zic1 and a novel player in the gene regulatory network controlling brain cell differentiation, along with some ganglions in Xenopus.

Osteoporosis in an Asian small-clawed otter (Aonyx cinereus Illiger, 1815).

Osteoporosis is a skeletal disease that occurs in many mammals. Our report describes osteoporosis in an Asian small-clawed otter (Aonyx cinereus). Gross, histological, and radiographic observations showed that all of the bones had numerous pockmarks on their surfaces. Histologically, the pockmarks were filled with fibrous tissue without inflammation. However, the spongy bone was normal according to the histological and radiographic results. Overall, the results showed that this was a case of osteoporosis that mainly involved external rather than internal surfaces.

Effects of regional body temperature variation during asphyxial cardiac arrest on mortality and brain damage in a rat model.

To date, hypothermia has focused on improving rates of resuscitation to increase survival in patients sustaining cardiac arrest (CA). Towards this end, the role of body temperature in neuronal damage or death during CA needs to be determined. However, few studies have investigated the effect of regional temperature variation on survival rate and neurological outcomes. In this study, adult male rats (12 week-old) were used under the following four conditions: (i) whole-body normothermia (37 ± 0.5 °C) plus (+) no asphyxial CA, (ii) whole-body normothermia + CA, (iii) whole-body hypothermia (33 ± 0.5 °C)+CA, (iv) body hypothermia/brain normothermia + CA, and (v) brain hypothermia/body normothermia + CA. The survival rate after resuscitation was significantly elevated in groups exposed to whole-body hypothermia plus CA and body hypothermia/brain normothermia plus CA, but not in groups exposed to whole-body normothermia combined with CA and brain hypothermia/body normothermia plus CA. However, the group exposed to hypothermia/brain normothermia combined with CA exhibited higher neuroprotective effects against asphyxial CA injury, i.e. improved neurological deficit and neuronal death in the hippocampus compared with those involving whole-body normothermia combined with CA. In addition, neurological deficit and neuronal death in the group of rat exposed to brain hypothermia/body normothermia and CA were similar to those in the rats subjected to whole-body normothermia and CA. In brief, only brain hypothermia during CA was not associated with effective survival rate, neurological function or neuronal protection compared with those under body (but not brain) hypothermia during CA. Our present study suggests that regional temperature in patients during CA significantly affects the outcomes associated with survival rate and neurological recovery.

Therapeutic hypothermia attenuates paraplegia and neuronal damage in the lumbar spinal cord in a rat model of asphyxial cardiac arrest.

Spinal cord ischemia can result from cardiac arrest. It is an important cause of severe spinal cord injury that can lead to serious spinal cord disorders such as paraplegia. Hypothermia is widely acknowledged as an effective neuroprotective intervention following cardiac arrest injury. However, studies on effects of hypothermia on spinal cord injury following asphyxial cardiac arrest and cardiopulmonary resuscitation (CA/CPR) are insufficient. The objective of this study was to examine effects of hypothermia on motor deficit of hind limbs of rats and vulnerability of their spinal cords following asphyxial CA/CPR. Experimental groups included a sham group, a group subjected to CA/CPR, and a therapeutic hypothermia group. Severe motor deficit of hind limbs was observed in the control group at 1 day after asphyxial CA/CPR. In the hypothermia group, motor deficit of hind limbs was significantly attenuated compared to that in the control group. Damage/death of motor neurons in the lumbar spinal cord was detected in the ventral horn at 1 day after asphyxial CA/CPR. Neuronal damage was significantly attenuated in the hypothermia group compared to that in the control group. These results indicated that therapeutic hypothermia after asphyxial CA/CPR significantly reduced hind limb motor dysfunction and motoneuronal damage/death in the ventral horn of the lumbar spinal cord following asphyxial CA/CPR. Thus, hypothermia might be a therapeutic strategy to decrease motor dysfunction by attenuating damage/death of spinal motor neurons following asphyxial CA/CPR.

Melatonin alleviates asphyxial cardiac arrest-induced cerebellar Purkinje cell death by attenuation of oxidative stress.

Although multiple reports using animal models have confirmed that melatonin appears to promote neuroprotective effects following ischemia/reperfusion-induced brain injury, the relationship between its protective effects and activation of autophagy in Purkinje cells following asphyxial cardiac arrest and cardiopulmonary resuscitation (CA/CPR) remains unclear. Rats used in this study were randomly assigned to 6 groups as follows; vehicle-treated sham operated group, vehicle-treated asphyxial CA/CPR operated group, melatonin-treated sham operated group, melatonin-treated asphyxial CA/CPR operated group, PDOT (a MT2 melatonin receptor antagonist) plus (+) melatonin-treated sham operated group and PDOT+melatonin-treated asphyxial CA/CPR operated group. Melatonin (20 mg/kg, i.p., 4 times before CA and 3 times after CA) treatment significantly improved survival rate and neurological deficit compared with the vehicle-treated asphyxial CA/CPR rats (survival rates ≥40% vs 10%), showing that melatonin treatment exhibited protective effect against asphyxial CA/CPR-induced Purkinje cell death. The protective effect of melatonin against CA/CPR-induced Purkinje cell death paralleled a remarkable attenuation of autophagy-like processes (Beclin-1, Atg7 and LC3), as well as a dramatic reduction in superoxide anion radical (O2·-), intense enhancements of CuZn superoxide dismutase (SOD1) and MnSOD (SOD2) expressions. Furthermore, the protective effect was notably reversed by treatment with PDOT, which is a selective MT2 antagonist. In brief, melatonin conferred neuroprotection against asphyxial CA/CPR-induced Purkinje cell death via inhibiting autophagic activation by reducing expressions of O2·- and increasing expressions of antioxidant enzymes, and suggests that MT2 is involved in neuroprotective effect of melatonin against Purkinje cell death caused by asphyxial CA/CPR.

Diethylstilbestrol induces morphological changes in the spermatogonia, Sertoli cells and Leydig cells of adult rat.

It is now established that diethylstilbestrol (DES) has damaging effects on the male reproductive system. However, to date there have been no studies morphological analysis of adult rat testes upon treatment with DES. Here, we examined whether DES has any significant morphological effect on steroidogenesis and spermatogenesis. DES was injected subcutaneously at 3 µg/day and 30 µg/day in adult male Sprague-Dawley (SD) rats for two different treatment lengths (1 or 3 weeks), after which rats were necropsied. TUNEL labeling, cell counting, and morphological analysis were used to evaluate the effects of DES. A high dose of DES and longer exposure severely affected the cellular development of the testis. Specifically, DES treatment disrupted both steroidogenesis and spermatogenesis by decreasing the number of spermatogonia, Sertoli cells, and Leydig cells in a dose- and time-dependent manner. Thus, DES may account for decreases in the number of spermatogenic cells, Sertoli cells and Leydig cells, which in turn may lead to reduced fertility in males.

Correction: Akanda, M.R., et al., Anti-Inflammatory and Gastroprotective Roles of Rabdosia inflexa through Downregulation of Pro-Inflammatory Cytokines and MAPK/NF-κB Signaling Pathways. Int. J. Mol. Sci. 2018, 19, 584.

The authors wish to make the following corrections to this paper [...].