Network pharmacology and experimental evidence: ERK/CREB/BDNF signaling pathway is involved in the antidepressive roles of Kaiyu Zhishen decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Major Depressive Disorder (MDD) emerges as a complex psychosomatic condition, notable for its considerable suicidality and mortality rates. Increasing evidence suggests the efficacy of Chinese herbal medicine in mitigating depression symptoms and offsetting the adverse effects associated with conventional Western therapeutics. Notably, clinical trials have revealed the adjunctive antidepressant potential of Kaiyu Zhishen Decoction (KZD) alongside Western medication. However, the standalone antidepressant efficacy of KZD and its underlying mechanisms merit in-depth investigation. AIM OF THE STUDY: This research aims to elucidate the impact of KZD on MDD and delineate its mechanistic pathways through integrated network pharmacological assessments and empirical in vitro and in vivo analyses. MATERIALS AND METHODS: To ascertain the optimal antidepressant dosage and mechanism of KZD, a Chronic Unpredictable Mild Stress (CUMS)-induced depression model in mice was established to evaluate depressive behaviors. High-Performance Liquid Chromatography (HPLC) and network pharmacological approaches were employed to predict KZD's antidepressant mechanisms. Subsequently, hippocampal samples were subjected to 4D-DIA proteomic sequencing and validated through Western blot, immunofluorescence, Nissl staining, and pathway antagonist applications. Additionally, cortisol-stimulated PC12 cells were utilized to simulate neuronal damage, analyzing protein and mRNA levels of MAPK-related signals and cell proliferation markers. RESULTS: The integration of network pharmacology and HPLC identified kaempferol and quercetin as KZD's principal active compounds for MDD treatment. Proteomic and network pharmacological KEGG pathway analyses indicated the MAPK signaling pathway as a critical regulatory mechanism for KZD's therapeutic effect on MDD. KZD was observed to mitigate CUMS-induced upregulation of p-ERK/ERK, CREB, and BDNF protein expressions in hippocampal cells by attenuating oxidative stress, thereby ameliorating neuronal damage and exerting antidepressant effects. The administration of PD98059 counteracted KZD's improvements in depression-like behaviors and downregulated p-ERK/ERK and BDNF protein expressions in the hippocampus. CONCLUSIONS: This investigation corroborates KZD's pivotal, dose-dependent role in antidepressant activity. Both in vivo and in vitro experiments demonstrate KZD's capacity to modulate the ERK-CREB-BDNF signaling pathway by diminishing ROS expression induced by oxidative stress, enhancing neuronal repair, and thus, manifesting antidepressant properties. Accordingly, KZD represents a promising herbal candidate for further antidepressant research.

The Combination of Serum BDNF, Cortisol and IFN-Gamma Can Assist the Diagnosis of Major Depressive Disorder.

PURPOSE: Misdiagnosis and ineffective treatment are common in major depressive disorder (MDD) in current clinical practice, while the combination of various serum proteins may assist the correct diagnosis. The study aimed to explore whether the combination of serum inflammatory, stress, and neurotrophic factors could be helpful for the diagnosis of MDD and to investigate the predictors associated with early symptom improvements. PATIENTS AND METHODS: Baseline serum levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10, IL-1beta, tumor necrosis factor (TNF)-alpha, interferon (INF)-gamma, cortisol, and brain-derived neurotrophic factor (BDNF) were detected in 30 MDD patients and 30 age- and gender-matched healthy controls. 17-item Hamilton Depression Rating Scale (HAMD-17) and Hamilton Anxiety Rating Scale (HAMA) were applied to assess symptoms both at baseline and two weeks after antidepressant treatment. Stepwise multiple linear regression was employed to identify the early efficacy predictors, and a logistic regression model was built with the above serum proteins. The area under the receiver operating characteristic (AUC) curve was calculated to evaluate the model's diagnostic power. RESULTS: Multiple linear regression revealed that baseline scores of retardation (ß = -0.432, P = 0.012) and psychological anxiety (ß = -0.423, P = 0.014) factors were negatively associated with the reduction rate of HAMD-17. A simple and efficient diagnostic model using serum BDNF, cortisol, and IFN-gamma levels was established by the forward stepwise logistic regression, and the model achieved an AUC of 0.884, with 86.7% sensitivity and 83.3% specificity. CONCLUSION: The results showed that combining serum BDNF, cortisol and IFN-gamma could aid the diagnosis of MDD, while baseline retardation and psychological anxiety may predict the poor early symptom improvement.

Guanidine derivative polymer coated microbubble resonator for high sensitivity detection of CO2 gas concentration.

A carbon dioxide (CO2) gas sensor based on a polyhexamethylene biguanide (PHMB)-coated whispering gallery mode (WGM) microbubble resonator is proposed and verified experimentally in this work. Microbubbles were fabricated using two reverse arc discharges focused on microcapillaries. The inner wall of the microbubble was coated with a layer of PHMB using a filling and sintering process. A significant WGM resonance was observed by coupling with a tapered fiber. The experimental results show that as the concentration of carbon dioxide increases, a blue shift appears in the spectrum. Addition, a high sensitivity (0.46 pm /ppm) and a good linear relationship were obtained in the measurement range of 200-700 ppm with a detection limit of 50 ppm. The sensor features include high sensitivity, simple structure, easy manufacture, and low cost.

Clinical practice guidelines for post-stroke depression in China

Post-stroke depression (PSD) is a very common complication that leads to increased physical disability, poor functional outcome, and higher mortality. Therefore, early detection and treatment are very important. Since there are currently no specific guidelines for this disorder in China, the purpose of this study was to develop PSD guidelines and provide suggestions for clinicians and related workers.

Abnormal cerebral functional connectivity in esophageal cancer patients with theory of mind deficits in resting state.

OBJECTIVE: To explore the function of the default mode network (DMN) in the psychopathological mechanisms of theory of mind deficits in patients with an esophageal cancer concomitant with depression in resting the state. SUBJECTS AND METHODS: Twenty-five cases of esophageal cancer with theory of mind deficits (test group) that meet the diagnostic criteria of esophageal cancer and neuropsychological tests, including Beck depression inventory, reading the mind in the eyes, and Faux pas, were included, Another 25 cases of esophageal cancer patients but without theory of mind deficits (control group) were enrolled. Each patient completed a resting-state functional magnetic resonance imaging. RESULTS: The functional connectivity intensities within the cerebral regions in the DMN of all the enrolled patients were analyzed. The results of each group were compared. The functional connectivity of the bilateral prefrontal central region with the precuneus, bilateral posterior cingulate gyrus and bilateral ventral anterior cingulate gyrus in the patients of the test group were all reduced significantly (P < 0.05). In the resting state, the functional connectivity is abnormal in the cerebral regions in the DMN of esophageal cancer patients with theory of mind deficits. CONCLUSIONS: The theory of mind deficits might have an important function in the pathogenesis of esophageal cancer.

Theory of mind deficits in patients with esophageal cancer combined with depression.

AIM: To characterize the two components of theory of mind (ToM) in patients with esophageal cancer combined with depression. METHODS: Sixty-five patients with esophageal cancer combined with depression (depressed group) and 62 normal controls (control group) were assessed using reading the mind in the eyes test, faux pas task, verbal fluency test, digit span test and WAIS IQ test. The depressed group was divided into two subgroups including psychotic depressed (PD) group (32 cases) and nonpsychotic depressed (NPD) group (33 cases). The clinical symptoms of patients were assessed using Beck depression inventory version II and brief psychiatric reacting scale (BPRS). RESULTS: There was a significant difference between the depressed group and the control group on tasks involving ToM social perceptual components (mind reading: t = 7.39, P < 0.01) and tests involving ToM social cognitive components (faux pas questions: t = 13.75, P < 0.01), respectively. A significant difference was also found among the PD group, the NPD group and the control group on mind reading (F = 32.98, P < 0.01) and faux pas questions (χ² = 78.15, P < 0.01), respectively. The PD group and NPD group performed worse than normal group controls both on mind reading and faux pas questions (P < 0.05). The PD group performed significantly worse than the NPD group on tasks involving ToM (mind reading: F = 18.99, P < 0.01; faux pas questions: F = 36.01, P < 0.01). In the depressed group, there was a negative correlation between ToM performances and BPRS total score (mind reading: r = -0.35, P < 0.01; faux pas questions: r = -0.51, P < 0.01), and between ToM performances and hostile suspiciousness factor score (mind reading: r = -0.75, P < 0.01; faux pas questions: r = -0.73, P < 0.01), respectively. CONCLUSION: The two components of ToM are both impaired in patients with esophageal cancer combined with depression. This indicates that there may be an association between ToM deficits and psychotic symptoms in clinical depression.

Genetic variation in the calcium/calmodulin-dependent protein kinase (CaMK) pathway is associated with antidepressant response in females.

OBJECTIVE: Antidepressant effects on monoamine neurotransmission may be influenced by genetic variation in intracellular signal transduction pathways, such as the cyclic adenosine monophosphate (cAMP)--protein kinase A (PKA) pathway, Ras-mitogen activated protein kinase (MAPK) pathway and calcium/calmodulin-dependent protein kinase (CaMK) pathway. The aims of this study were to examine the association of polymorphisms in candidate genes of these three signal transduction pathways with response to antidepressant treatment, and to determine the effects of, and interactions with, environment factors. METHODS: We recruited 412 patients who met diagnosis criteria for major depressive disorder (MDD) (DSM-IV Axis I). 284 patients completed 8 weeks treatment with selective serotonin reuptake inhibitors (SSRIs) or serotonin and noradrenergic reuptake inhibitors (SNRIs). Severity of depression was measured with the Hamilton Depression Rating Scale (HDRS) before and after 8 weeks antidepressant treatment. 209 patients completed the Childhood Trauma Questionnaire, 28 item Short Form (CTQ-SF) which was used to evaluate childhood adverse events. 218 patients completed the Life Events Scale (LES) which were used to evaluate life stress before onset. 155 SNPs in 66 candidate genes were genotyping by Illumina GoldenGate, including 28 SNPs in 15 genes of cAMP-PKA pathway, 37 SNPs in 17 genes of Ras-MAPK pathway and 90 SNPs in 34 genes of CaMK pathway. The remission criterion was HDRS score equal to or less than 7. Single SNP and haplotype associations were analyzed by UNPHASED 3.3.13. Gene-environment interactions were analyzed by binary logistic regression with SPSS 11.0 software. RESULTS: The rs2230372 SNP in ITPR2, rs2280272 in PRKCZ, rs17109671, and rs17109674 in PLCE1 were significant associated with remission, as were haplotypes in PRKCZ and PLCE1. All these positive associations were found in genes of the CaMK pathway, but not the cAMP-PKA or Ras-MAPK pathways. There were no significant differences in CTQ scores and LES scores between remitters and non-remitters. No significantly interactions between candidate genes and environment effects were observed. CONCLUSION: The CaMK pathway may be important in determining antidepressant response. But recent adverse life events, childhood adversity, and interactions between candidate genes and environment factors appear not to influence short term antidepressant outcome.