Protective effects of Pudilan Tablets against osteoarthritis in mice induced by monosodium iodoacetate.

Osteoarthritis (OA) is a complicated disorder that is the most prevalent chronic degenerative joint disease nowadays. Pudilan Tablets (PDL) is a prominent traditional Chinese medicine formula used in clinical settings to treat chronic inflammatory illnesses. However, there is currently minimal fundamental research on PDL in the therapy of joint diseases. As a result, this study looked at the anti-inflammatory and anti-OA properties of PDL in vitro and in vivo, as well as the mechanism of PDL in the treatment of OA. We investigated the anti-OA properties of PDL in OA mice that were generated by monosodium iodoacetate (MIA). All animals were administered PDL (2 g/kg or 4 g/kg) or the positive control drug, indomethacin (150 mg/kg), once daily for a total of 28 days starting on the day of MIA injection. The CCK-8 assay was used to test the vitality of PDL-treated RAW264.7 cells in vitro. RAW264.7 cells that had been activated with lipopolysaccharide (LPS) were used to assess the anti-inflammatory properties of PDL. In the MIA-induced OA model mice, PDL reduced pain, decreased OA-induced cartilage damages and degradation, decreased production of pro-inflammatory cytokines in serum, and suppressed IL-1ß, IL-6, and TNF-α mRNA expression levels in tibiofemoral joint. In RAW264.7 cells, PDL treatment prevented LPS-induced activation of the ERK/Akt signaling pathway and significantly decreased the levels of inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α. In conclusion, these results suggest that PDL is involved in combating the development and progression of OA, exerts a powerful anti-inflammatory effect on the knee joint, and may be a promising candidate for the treatment of OA.

Correlation of Glucose Metabolism with Cancer and Intervention with Traditional Chinese Medicine.

Cancer is a complex disease with several distinct characteristics, referred to as "cancer markers" one of which is metabolic reprogramming, which is a common feature that drives cancer progression. Over the last ten years, researchers have focused on the reprogramming of glucose metabolism in cancer. In cancer, the oxidative phosphorylation metabolic pathway is converted into the glycolytic pathway in order to meet the growth requirements of cancer cells, thereby creating a microenvironment that promotes cancer progression. The precise mechanism of glucose metabolism in cancer cells is still unknown, but it is thought to involve the aberrant levels of metabolic enzymes, the influence of the tumor microenvironment (TME), and the activation of tumor-promoting signaling pathways. It is suggested that glucose metabolism is strongly linked to cancer progression because it provides energy to cancer cells and interferes with antitumor drug pharmacodynamics. Therefore, it is critical to unravel the mechanism of glucose metabolism in tumors in order to gain a better understanding of tumorigenesis and to lay the groundwork for future research into the identification of novel diagnostic markers and therapeutic targets for cancer treatment. Traditional Chinese Medicine (TCM) has the characteristics of multiple targets, multiple components, and less toxic side effects and has unique advantages in tumor treatment. In recent years, researchers have found that a variety of Chinese medicine monomers and compound recipes play an antitumor role by interfering with the reprogramming of tumor metabolism. The underlying mechanisms of metabolism reprogramming of tumor cells and the role of TCM in regulating glucose metabolism are reviewed in this study, so as to provide a new idea for antitumor research in Chinese medicine.

Frequency-Dependent Plasticity in the Temporal Association Cortex Originates from the Primary Auditory Cortex, and Is Modified by the Secondary Auditory Cortex and the Medial Geniculate Body.

The brain areas that mediate the formation of auditory threat memory and perceptual decisions remain uncertain to date. Candidates include the primary (A1) and secondary (A2) auditory cortex, the medial division of the medial geniculate body (MGm), amygdala, and the temporal association cortex. We used chemogenetic and optogenetic manipulations with in vivo and in vitro patch-clamp recordings to assess the roles of these brain regions in threat memory learning in female mice. We found that conditioned sound (CS) frequency-dependent plasticity resulted in the formation of auditory threat memory in the temporal association cortex. This neural correlated auditory threat memory depended on CS frequency information from A1 glutamatergic subthreshold monosynaptic inputs, CS lateral inhibition from A2 glutamatergic disynaptic inputs, and non-frequency-specific facilitation from MGm glutamatergic monosynaptic inputs. These results indicate that the A2 and MGm work together in an inhibitory-facilitative role.SIGNIFICANCE STATEMENT: The ability to recognize specific sounds to avoid predators or seek prey is a useful survival tool. Improving this ability through experiential learning is an added advantage requiring neural plasticity. As an example, humans must learn to distinguish the sound of a car horn, and thus avoid oncoming traffic. Our research discovered that the temporal association cortex can encode this kind of auditory information through tonal receptive field plasticity. In addition, the results revealed the underlying synaptic mechanisms of this process. These results extended our understanding of how meaningful auditory information is processed in an animal's brain.

Identifying Active Substances and the Pharmacological Mechanism of Houttuynia cordata Thunb. in Treating Radiation-Induced Lung Injury Based on Network Pharmacology and Molecular Docking Verification.

Background: Houttuynia cordata Thunb. is a traditional Chinese herb widely used mainly because of the pharmacological effects related to heat clearance and detoxification. Emerging clinical evidence indicates that the efficacy of Houttuynia cordata Thunb. on RILI is upstanding. Nevertheless, its underlying therapeutic mechanism remains unclear and warrants further elucidation. Methods: The major active components and corresponding targets of Houttuynia cordata Thunb. were retrieved from the traditional Chinese medicine system pharmacology database (TCMSP) and literature review. The related targets of RILI were retrieved from the GeneCards database. Common targets among the active compounds and diseases were identified through Venn diagram analysis. Cytoscape was employed to construct and visualize the network relationship among the drug, active compounds, targets, and disease. The protein interaction network (PPI) was constructed by STRING. The reliability (the binding affinity) of the core targets and active compounds was verified by molecular docking. Results: A search of the TCMSP database and related literature revealed 12 active compounds of Houttuynia cordata Thunb. against RILI. The core active compounds included quercetin, kaempferol, hyperoside, and rutin. Hub nodes including TP53, VEGFA, JUN, TNF, and IL-6 were identified in the PPI network. The GO categories were classified into three functional categories: 112 biological processes, 9 molecular functions, and 32 cellular components of the active compounds of Houttuynia cordata Thunb. The KEGG pathway enrichment analysis demonstrated the enrichment of target genes in several key cancer-related signaling pathways, including the cancer pathways, TNF signaling pathway, PI3K-Akt signaling pathway, and HIF-1 signaling pathway. Molecular docking analysis validated the effective binding capacity of the main active compounds with the core targets. Conclusion: The main active components of Houttuynia cordata Thunb. have a potential pharmacological effect against RILI via the cancer pathways, TNF signaling pathway, and PI3K-Akt signaling pathway.

Individualized Prediction of Survival Benefits of Pancreatectomy Plus Chemotherapy in Patients With Simultaneous Metastatic Pancreatic Cancer.

BACKGROUND: Metastatic pancreatic cancer (mPC) is a highly lethal malignancy with poorer survival. However, chemotherapy alone was unable to maintain long-term survival. This study aimed to evaluate the individualized survival benefits of pancreatectomy plus chemotherapy (PCT) for mPC. METHODS: A total of 4546 patients with mPC from 2004 to 2015 were retrieved from the Surveillance, Epidemiology, and End Results database. The survival curve was calculated using the Kaplan-Meier method and differences in survival curves were tested using log-rank tests. Cox proportional hazards regression analyses were performed to evaluate the prognostic value of involved variables. A new nomogram was constructed to predict overall survival based on independent prognosis factors. The performance of the nomogram was measured by concordance index, calibration plot, and area under the receiver operating characteristic curve. RESULTS: Compared to pancreatectomy or chemotherapy alone, PCT can significantly improve the prognosis of patients with mPC. In addition, patients with well/moderately differentiated tumors, age ≤66 years, tumor size ≤42 mm, or female patients were more likely to benefit from PCT. Multivariate analysis showed that age at diagnosis, sex, marital status, grade, tumor size, and treatment were independent prognostic factors. The established nomogram has a good ability to distinguish and calibrating. CONCLUSION: PCT can prolong survival in some patients with mPC. Our nomogram can individualize predict OS of pancreatectomy combined with chemotherapy in patients with concurrent mPC.

Filling a Gap: The Coordinatively Saturated Group†4 Carbonyl Complexes TM(CO)8 (TM=Zr, Hf) and Ti(CO)7.

Homoleptic Group 4 metal carbonyl cation and neutral complexes were prepared in the gas phase and/or in solid neon matrix. Infrared spectroscopy studies reveal that both zirconium and hafnium form eight-coordinate carbonyl neutral and cation complexes. In contrast, titanium forms only the six-coordinate Ti(CO)6 + and seven-coordinate Ti(CO)7 . Titanium octacarbonyl Ti(CO)8 is unstable as a result of steric repulsion between the CO ligands. The 20-electron Zr(CO)8 and Hf(CO)8 complexes represent the first experimentally observed homoleptic octacarbonyl neutral complexes of transition metals. The molecules still fulfill the 18-electron rule, because one doubly occupied valence orbital does not mix with any of the metal valence atomic orbitals. Zr(CO)8 and Hf(CO)8 are stable against the loss of one CO because the CO ligands encounter less steric repulsion than Zr(CO)7 and Hf(CO)7 . The heptacarbonyl complexes have shorter metal-CO bonds than that of the octacarbonyl complexes due to stronger electrostatic and covalent bonding, but the significantly smaller repulsive Pauli term makes the octacarbonyl complexes stable.

Octa-coordinated alkaline earth metal-dinitrogen complexes M(N2)8 (M=Ca, Sr, Ba).

We report the isolation and spectroscopic identification of the eight-coordinated alkaline earth metal-dinitrogen complexes M(N2)8 (M=Ca, Sr, Ba) possessing cubic (Oh) symmetry in a low-temperature neon matrix. The analysis of the electronic structure reveals that the metal-N2 bonds are mainly due to [M(dπ)]→(N2)8 π backdonation, which explains the observed large red-shift in N-N stretching frequencies. The adducts M(N2)8 have a triplet (3A1g) electronic ground state and exhibit typical bonding features of transition metal complexes obeying the 18-electron rule. We also report the isolation and bonding analysis of the charged dinitrogen complexes [M(N2)8]+ (M=Ca, Sr).

Octacarbonyl Anion Complexes of the Late Lanthanides Ln(CO)8 - (Ln=Tm, Yb, Lu) and the 32-Electron Rule.

The lanthanide octacarbonyl anion complexes Ln(CO)8 - (Ln=Tm, Yb, Lu) were produced in the gas phase and detected by mass-selected infrared photodissociation spectroscopy in the carbonyl stretching-frequency region. By comparison of the experimental CO-stretching frequencies with calculated data, which are strongly red-shifted with respect to free CO, the Yb(CO)8 - and Lu(CO)8 - complexes were determined to possess octahedral (Oh ) symmetry and a doublet X2 A2u (Yb) and singlet X1 A1g (Lu) electronic ground state, whereas Tm(CO)8 - exhibits a D4h equilibrium geometry and a triplet X3 B1g ground state. The analysis of the electronic structures revealed that the metal-CO attractive forces come mainly from covalent orbital interactions, which are dominated by [Ln(d)]→(CO)8 π backdonation and [Ln(d)]←(CO)8 σ donation (contributes ≈77 and 16 % to covalent bonding, respectively). The metal f orbitals play a very minor role in the bonding. The electronic structure of all three lanthanide complexes obeys the 32-electron rule if only those electrons that occupy the valence orbitals of the metal are considered.