Gegen Qinlian decoction alleviates depression-like behavior by modulating the gut microenvironment in CUMS rats.

Background: Gegen Qinlian Decoction (GQD) is a classical traditional Chinese medicine (TCM) formula primarily utilized for treating gut disorders. GQD showed therapeutic effects on several diseases in clinical and animal studies by targeting gut microbes. Our recent studies also found that GQD efficiently alleviated anxiety in methamphetamine-withdrawn mice via regulating gut microbiome and metabolism.

MRE11A: a novel negative regulator of human DNA mismatch repair.

Background: DNA mismatch repair (MMR) is a highly conserved pathway that corrects DNA replication errors, the loss of which is attributed to the development of various types of cancers. Although well characterized, MMR factors remain to be identified. As a 3'-5' exonuclease and endonuclease, meiotic recombination 11 homolog A (MRE11A) is implicated in multiple DNA repair pathways.

METH exposure alters sperm DNA methylation in F0 mice and mPFC transcriptome in male F1 mice.

Rationale: Methamphetamine (METH) exposure has toxicity in sperm epigenetic phenotype and increases the risk for developing addiction in their offspring. However, the underlying transgenerational mechanism remains unclear.

Objectives: The current study aims to investigate the profiles of sperm epigenetic modifications in male METH-exposed mice (F0) and medial prefrontal cortex (mPFC) transcriptome in their male first-generation offspring (F1).

Paternal methamphetamine exposure induces higher sensitivity to methamphetamine in male offspring through driving ADRB1 on CaMKII-positive neurons in mPFC.

Paternal abuse of drugs, such as methamphetamine (METH), elevates the risk of developing addiction in subsequent generations, however, its underlying molecular mechanism remains poorly understood. Male adult mice (F0) were exposed to METH for 30 days, followed by mating with naïve female mice to create the first-generation mice (F1). When growing to adulthood, F1 were subjected to conditioned place preference (CPP) test.

Zinc depletion induces JNK/p38 phosphorylation and suppresses Akt/mTOR expression in acute promyelocytic NB4 cells.

Background: Myeloid leukemia is associated with reduced serum zinc and increased intracellular zinc. Our previous studies found that zinc depletion by TPEN induced apoptosis with PML-RARα oncoprotein degradation in acute promyelocytic NB4 cells. The effect of zinc homeostasis on intracellular signaling pathways in myeloid leukemia cells remains unclear.

Gegen-Qinlian decoction alleviates anxiety-like behaviors in methamphetamine-withdrawn mice by regulating Akkermansia and metabolism in the colon.

Background: Anxiety is a prominent withdrawal symptom of methamphetamine (Meth) addiction. Recently, the gut microbiota has been regarded as a promising target for modulating anxiety. Gegen-Qinlian decoction (GQD) is a classical Traditional Chinese Medicine applied in interventions of various gut disorders by balancing the gut microbiome.

Sex-specific neurobehavioural outcomes and brain stimulation pattern in adult offspring paternally exposed to methamphetamine.

Paternal methamphetamine (METH) exposure results in long-term behavioural deficits in the sub-generations with a sex difference. Here, we aim to investigate the sex-specific neurobehavioural outcomes in the first-generation offspring mice (F1 mice) paternally exposed to METH prior to conception and explore the underlying brain mechanisms. We found that paternal METH exposure increased anxiety-like behaviours and spatial memory deficits only in female F1 mice and caused depression-like behaviours in the offspring without sex-specific differences.

CNOT6: A Novel Regulator of DNA Mismatch Repair.

DNA mismatch repair (MMR) is a highly conserved pathway that corrects both base-base mispairs and insertion-deletion loops (IDLs) generated during DNA replication. Defects in MMR have been linked to carcinogenesis and drug resistance. However, the regulation of MMR is poorly understood.

Dynamic expression of FAM83D in peripheral organs at different ages in mice.

The family with sequence similarity 83 member (FAM83D) plays important role in the process of cell division as well as tumour progression. However, the role of FAM83D in tissue development was not well explored. Here, we assessed transcriptional levels of FAM83D and other possibly related genes in organs of mice at different ages and methylation level of FAM83D promoter.

Astrocyte-selective STAT3 knockdown rescues methamphetamine withdrawal-disrupted spatial memory in mice via restoring the astrocytic capacity of glutamate clearance in dCA1.

Methamphetamine (METH) is a common abused drug. METH-triggered glutamate (Glu) levels in dorsal CA1 (dCA1) could partially explain the etiology of METH-caused abnormal memory, but the synaptic mechanism remains unclear. Here, we found that METH withdrawal disrupted spatial memory in mice, accompanied by the increases in Glu levels and postsynaptic neuronal activities at dCA1 synapses.

Zi Shen Decoction Inhibits Growth and Metastasis of Lung Cancer via Regulating the AKT/GSK-3/-Catenin Pathway.

Lung cancer has become the leading cause of cancer-related death worldwide. Oxidative stress plays important roles in the pathogenesis of lung cancer. Many natural products show antioxidative activities in cancer treatment.

Human DNA polymerase delta double-mutant D316A;E318A interferes with DNA mismatch repair in vitro.

DNA mismatch repair (MMR) is a highly-conserved DNA repair mechanism, whose primary role is to remove DNA replication errors preventing them from manifesting as mutations, thereby increasing the overall genome stability. Defects in MMR are associated with increased cancer risk in humans and other organisms. Here, we characterize the interaction between MMR and a proofreading-deficient allele of the human replicative DNA polymerase delta, PolδD316A;E318A, which has a higher capacity for strand displacement DNA synthesis than wild type Polδ.

DNA mismatch repair and its many roles in eukaryotic cells.

DNA mismatch repair (MMR) is an important DNA repair pathway that plays critical roles in DNA replication fidelity, mutation avoidance and genome stability, all of which contribute significantly to the viability of cells and organisms. MMR is widely-used as a diagnostic biomarker for human cancers in the clinic, and as a biomarker of cancer susceptibility in animal model systems. Prokaryotic MMR is well-characterized at the molecular and mechanistic level; however, MMR is considerably more complex in eukaryotic cells than in prokaryotic cells, and in recent years, it has become evident that MMR plays novel roles in eukaryotic cells, several of which are not yet well-defined or understood.

Involvement of the DNA mismatch repair system in cisplatin sensitivity of testicular germ cell tumours.

Background: Testicular germ cell tumours (TGCT) are highly sensitive to cisplatin-based chemotherapy, but patients with tumours containing differentiated teratoma components are less responsive to this treatment. The cisplatin sensitivity in TGCT has previously been linked to the embryonic phenotype in the majority of tumours, although the underlying mechanism largely remains to be elucidated. The aim of this study was to investigate the role of the DNA mismatch repair (MMR) system in the cisplatin sensitivity of TGCT.

Exonuclease 1 and its versatile roles in DNA repair.

Exonuclease 1 (EXO1) is a multifunctional 5' → 3' exonuclease and a DNA structure-specific DNA endonuclease. EXO1 plays roles in DNA replication, DNA mismatch repair (MMR) and DNA double-stranded break repair (DSBR) in lower and higher eukaryotes and contributes to meiosis, immunoglobulin maturation, and micro-mediated end-joining in higher eukaryotes. In human cells, EXO1 is also thought to play a role in telomere maintenance.

Adverse effects of 2,2',4,4'-tetrabromodiphenyl ether on semen quality and spermatogenesis in male mice.

2,2',4,4'-Tetrabromodiphenyl ether (BDE47) is an environmental contaminant. To determine the reproductive toxicity, we studied groups of adult male mice and found that the rate of sperm capacitation was decreased significantly in three BDE47-exposed groups (0.0015, 0.

Inactivation of Dicer1 has a severe cumulative impact on the formation of mature germ cells in mouse testes.

Dicer1, an RNase III endonuclease, is indispensable for the maturation of miRNA and siRNA, which control gene expression through the RNAi pathway. The diverse functions of miRNA involving multiple developmental processes have been elucidated, but the role of Dicer1 in spermatogenesis is just beginning to be revealed. Mice lacking Dicer1 were reported to be embryonic lethal at E7.

Effect of low-dose fenvalerate on semen quality capacitation in adult mice.

Background: Fenvalerate (FEN) has been demonstrated to be a reproductive toxicant in humans and rodents. However, little is known about whether short-term exposure to low-dose FEN produces reproductive toxicity.

Methods: We administered FEN (0.