Time Course of Biochemical and Metabolic Parameters During and After COVID-19.

BACKGROUND: Long COVID is characterized by the persistence of symptoms among individuals who are infected with the SARS-CoV-2 virus. The enduring impact of these long-term effects on the health and well-being of those affected cannot be denied. METHOD: About 470 patients with SARS-CoV-2 were consecutively recruited in this longitudinal study. The participants were entered into moderate, severe, and critical groups. 235 out of 470 participants were female. The levels of fasting blood sugar (FBS), alanine transaminase (SGPT), aspartate aminotransferase (SGOT), alkaline phosphatase (ALP), creatinine (Cr), urea, uric acid (UA), and total protein (TP) were measured during hospitalization and again at one and three months after infection. The levels of Zn and hemoglobin A1c (HbA1c) were also measured only during hospitalization. RESULT: COVID-19 severity was associated with high levels of glucose, urea, Cr, ALT, AST, ALP, and HbA1c, and low levels of Zn, UA, and TP. There were significant sex differences for these markers at all three-time points. Glucose, urea, Cr, ALT, AST, and ALP all decreased three months after infection, whereas the levels of UA and TP returned towards normal. CONCLUSION: COVID-19 infection affects the levels of multiple biochemical factors in a gender-dependent manner. The biochemical changes become more tangible with increasing disease severity, and several of these predict mortality. Levels begin to return to normal after the acute phase of the disease, but in some individuals, at three months, several markers were still not within the normal range. Whether the trajectory of these changes can predict long COVID requires further testing.

The different role of G-protein-coupled receptor 30 (GPR30) in the interaction effects of marijuana and estradiol on spatial learning and memory at different ages.

Some studies suggest that the effect of cannabis on behavior performance depends on the presence of ovarian hormones and the age of use initiation. Estradiol is the main ovarian hormone that can interact with cannabinoids. It has been suggested that cannabinoids exert some of their effects directly through estrogen receptors (ERs). A novel G-protein-coupled receptor (GPR30) was described as mediating estrogen signaling in various cell lines. Since there are few studies on the interaction of cannabis and ovarian hormones on cognitive behaviors, so, this study evaluated the role of GPR30 in the effects of marijuana (M) and estrogen, alone and in combination, on spatial learning and memory of young (non-ovarian(OVX)) and old female rats. Young (5-7 months) and old (22-24 months) female rats received an intraperitoneal injection (i.p) of 17ß-estradiol (E2), G1 (GPR30 agonist), and G15 (GPR30 antagonist) every four days, and M (every day), either alone or in combination, for 28 days. One hour after the last injection, the Morris water maze (MWM) test was conducted to evaluate of spatial learning and memory. Moreover, hippocampal BDNF level was assessed by the ELISA method. The results showed a positive effect of M on spatial learning in both young and old rats, however, E2 showed beneficial effects on the memory of young, but not old rats. Our results showed that GPR30 does not have any role in the interaction effects of M and E2 in young rats. Although both E2 and M alone showed positive effects on spatial learning and memory in old rats, however, our results showed a negative interaction between marijuana and E2 combined effects on spatial learning and memory in old female rats which is mediated by GPR30. Our results showed that the effects of GPR30 on spatial learning and memory is age dependent. Furthermore, this study showed that hippocampal BDNF does not have any role in the interaction effects of M and E2 on spatial learning and memory in young and old rats.

Protective Roles of Shilajit in Modulating Resistin, Adiponectin, and Cytokines in Rats with Non-alcoholic Fatty Liver Disease / 中国结合医学杂志

OBJECTIVE@#To evaluate the effect of Shilajit, a medicine of Ayurveda, on the serum changes in cytokines and adipokines caused by non-alcoholic fatty liver disease (NAFLD).@*METHODS@#After establishing fatty liver models by feeding a high-fat diet (HFD) for 12 weeks, 35 Wistar male rats were randomly divided into 5 groups, including control (standard diet), Veh (HFD + vehicle), high-dose Shilajit [H-Sh, HFD + 250 mg/(kg·d) Shilajit], low-dose Shilajit [L-Sh, HFD + 150 mg/(kg·d) Shilajit], and pioglitazone [HFD + 10 mg/(kg·d) pioglitazone] groups, 7 rats in each group. After 2-week of gavage administration, serum levels of glucose, insulin, interleukin 1beta (IL-1β), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), adiponectin, and resistin were measured, and insulin resistance index (HOMA-IR) was calculated.@*RESULTS@#After NAFLD induction, the serum level of IL-10 significantly increased and serum IL-1β, TNF-α levels significantly decreased by injection of both doses of Shilajit and pioglitazone (P<0.05). Increases in serum glucose level and homeostasis model of HOMA-IR were reduced by L-Sh and H-Sh treatment in NAFLD rats (P<0.05). Both doses of Shilajit increased adiponectin and decreased serum resistin levels (P<0.05).@*CONCLUSION@#The probable protective role of Shilajit in NAFLD model rats may be via modulating the serum levels of IL-1β, TNF-α, IL-10, adipokine and resistin, and reducing of HOMA-IR.

Using the NGF/IL-6 ratio as a reliable criterion to show the beneficial effects of progesterone after experimental diffuse brain injury.

Acute progesterone injection has been shown to reduce brain edema following traumatic brain injury (TBI) due to its neuroprotective effect. We investigated the effects of sustained release of progesterone through implantation of subcutaneous capsules on rat's brain edema and alteration of cerebrospinal fluid (CSF), and serum ratio of NGF/IL-6 after TBI. This experiment was performed on ovariectomized (OVX) rats and the brain injury was induced by Marmarou's method. A high and a low dose of progesterone (HP and LP) was injected intraperitoneally two h after the brain injury. In addition, in the capsule progesterone-treated group (CP), the intervention was implemented 6 h after the brain injury. Brain edema, NGF and IL-6 biomarkers in serum and cerebrospinal fluid (CSF) were measured 48 h after the TBI in injection groups and one week after the TBI in the CP group. No significant difference was found in the two groups or in the admonition methods. After TBI, the NGF level increased and IL-6 level decreased by injection of both doses, as well as by taking the capsule. Ratio of NGF/IL-6 in CSF increased significantly by all forms of progesterone administration. The increase in the level of NGF and IL-6 after TBI was higher in CSF than in serum. These results indicated that effects of progesterone in capsule form were better than the injection form. Progesterone probably works by increasing NGF and reducing IL-6. Future studies should investigate the ratio of these biomarkers as a variable to determine the neuroprotective effects of another drug.

Ellagic acid prevents cognitive and hippocampal long-term potentiation deficits and brain inflammation in rat with traumatic brain injury.

AIMS: Traumatic brain injury (TBI) remains one of the main clinical problems globally and is a common cause of death among youth. Cognitive defects such as thinking, memory and behavior or mental health disorders are considered as the most frequent effects of severe and moderate TBI. It has been reported that ellagic acid (EA), a natural polyphenol, exhibits protective effects against oxidative damage. This study was performed to examine the EA preventive effects on cognitive impairments, long-term potentiation (LTP) deficits in hippocampus and brain inflammation induced by diffuse TBI in rat. MAIN METHODS: Subchronic oral administration of 100 mg/kg EA, 7 consecutive days before induction of trauma (once daily) was used to elucidate the EA effects on passive avoidance memory and hippocampal LTP following TBI. To illustrate the possible mechanisms related to the preventive effects of EA on brain function following TBI, brain content of IL-1ß, IL-6 and blood-brain barrier (BBB) permeability were determined. KEY FINDINGS: EA pretreatment significantly (P<0.001) prevented TBI-induced memory and hippocampal LTP impairments in rat. Furthermore TBI induced elevation in brain content of IL-1ß, IL-6 and BBB permeability were decreased significantly (P<0.001) due to EA pre-treatment. SIGNIFICANCE: Our findings suggest that EA can prevent cognitive and LTP deficits and also prevent brain inflammation following TBI.

Changes in neuromedin S and its receptor after traumatic brain injury in cycling rats

Animal studies indicate that gonadal steroids have prominent neuroprotective effects in several models of experimental traumatic brain injury (TBI). Neuromedin U (NMU) and neuromedin S (NMS) are regulatory peptides involved in inflammatory and stress responses, and modulation of the gonadotropic axis. Since steroid hormone levels change during the estrous cycle, we sought to determine whether variations in ovarian hormones would affect blood-brain barrier (BBB) permeability and brain levels of NMS, NMU, and neuromedin S receptor 2 in experimental TBI. Two groups (proestrus and nonproestrus) of female rats underwent diffuse TBI. At 24 hrs after TBI, results showed a significantly decrease in BBB permeability in traumatic-proestrus animals (TBI-P) in comparison to traumatic nonproestrus (TBI-NP) rats. Western blot analyzes demonstrated an enhanced expression of prepro-NMS in TBI-P compared with that in the TBI-NP group. Likewise, TBI-P rats exhibited significantly higher NMUR2 gene expression compared with those of TBI-NP, whereas no significant difference in brain NMU content was seen between sham and traumatic animals. Our findings indicate that diffuse TBI induces an increase in prepro-NMS and neuromedin S receptor 2 expression in traumatic-proestrus rats which may mediate the anti-edematous effects of gonadal hormones in proestrus rats following trauma.

Changes in neuromedin S and its receptor after traumatic brain injury in cycling rats

Animal studies indicate that gonadal steroids have prominent neuroprotective effects in several models of experimental traumatic brain injury (TBI). Neuromedin U (NMU) and neuromedin S (NMS) are regulatory peptides involved in inflammatory and stress responses, and modulation of the gonadotropic axis. Since steroid hormone levels change during the estrous cycle, we sought to determine whether variations in ovarian hormones would affect blood-brain barrier (BBB) permeability and brain levels of NMS, NMU, and neuromedin S receptor 2 in experimental TBI. Two groups (proestrus and nonproestrus) of female rats underwent diffuse TBI. At 24 hrs after TBI, results showed a significantly decrease in BBB permeability in traumatic-proestrus animals (TBI-P) in comparison to traumatic nonproestrus (TBI-NP) rats. Western blot analyzes demonstrated an enhanced expression of prepro-NMS in TBI-P compared with that in the TBI-NP group. Likewise, TBI-P rats exhibited significantly higher NMUR2 gene expression compared with those of TBI-NP, whereas no significant difference in brain NMU content was seen between sham and traumatic animals. Our findings indicate that diffuse TBI induces an increase in prepro-NMS and neuromedin S receptor 2 expression in traumatic-proestrus rats which may mediate the anti-edematous effects of gonadal hormones in proestrus rats following trauma.

Neuroprotective antioxidant effect of sex steroid hormones in traumatic brain injury.

The aim of the present study was to evaluate the effect of different doses of sex steroid hormones on brain edema, BBB permeability, brain antioxidant enzyme activity, and MDA level after traumatic brain injury (TBI) in ovarectomized (OVX) rats. Female rats were divided into six (One sham and 5 TBI) groups including: vehicle, estrogen in physiologic (33.3 µg/kg) and pharmacologic (1mg/kg) doses, progesterone in physiologic (1.7 mg/kg) and pharmacological doses (8mg/kg). The results showed that compared to vehicle group, estrogen and progesterone groups showed significantly lower brain water content (P<0.001). Evans blue content was significantly lower in both estrogen doses and in progesterone physiologic dose (P<0.001). Evans blue content was significantly higher in progesterone pharmacologic dose (P<0.001). Superoxide dismutase (SOD) activity was significantly higher in estrogen and progesterone pharmacologic doses (P<0.001). Glutathione peroxidase (GPx) activity was significantly lower in estrogen physiologic dose (P<0.001). It was concluded that the neuroprotective effect of different doses of sex steroid hormones after TBI, may be mediated by changes in oxidant agent activity.

Chronic Opium Treatment Can Differentially Induce Brain and Liver Cells Apoptosis in Diabetic and Non-diabetic Male and Female Rats

It has been shown that some opium derivatives promote cell death via apoptosis. This study was designed to examine the influence of opium addiction on brain and liver cells apoptosis in male and female diabetic and non-diabetic Wistar rats. This experimental study was performed on normal, opium-addicted, diabetic and diabetic opium-addicted male and female rats. Apoptosis was evaluated by TUNEL and DNA fragmentation assays. Results of this study showed that apoptosis in opium-addicted and diabetic opium-addicted brain and liver cells were significantly higher than the both normal and diabetic rats. In addition, we found that apoptosis in brain cells of opium-addicted and diabetic opium-addicted male rats were significantly higher than opium-addicted and diabetic opium-addicted female, whereas apoptosis in liver cells of opium-addicted and diabetic opium-addicted female rats were significantly higher than opium-addicted and diabetic opium-addicted male. Overall, these results indicate that opium probably plays an important role in brain and liver cells apoptosis, therefore, leading neurotoxicity and hepatotoxicity. These findings also in away possibly means that male brain cells are more susceptible than female and interestingly liver of females are more sensitive than males in induction of apoptosis by opium.

Effect of trifluoperazine on carrageenan-induced acute inflammation in intact and adrenalectomized rats.

The aim of present study was to investigate the effect of trifluoperazine (TFP) on carrageenan-induced rat's paw edema in intact and adrenalectomized (ADX). TFP (0.2 and 8 mg/kg) were given intraperitoneally just before the intraplantar injection of 0.1 ml of 0.5% carrageenan solution. After four hours, paw edema was assessed by calculating the paw volume changes and extravasations of Evans blue dye as inflammatory indicators. In both ADX and control groups, administration of TFP reduced inflammatory parameters (paw volume and tissue content of Evans blue dye) in inflamed paw. Our findings suggest that TFP can effectively reduce carrageenan-induced paw edema in both ADX and control rats. Therefore, anti-inflammatory effect of these drugs does not need the adrenal gland activity.