The most prevalent form of dementia, Alzheimer’s disease (AD), is a neurological disorder that causes gradual memory loss. AD is characterized by amyloid-beta plaques, neurofibrillary tangles, and neuron loss. While preclinical and clinical trials are underway to reduce the generation and overall brain disease load, current treatment focuses on alleviating symptoms. Animal studies are essential for advancing our understanding of AD, identifying potential drug targets, and testing experimental therapies. An ideal animal model not only exhibits the same symptoms and pathological changes as a human disease but also follows the same sequence of pathological events. This review highlights the various inducing agents used to model AD in animals, such as streptozotocin, aluminium chloride, trimethyltin, lipopolysaccharide, scopolamine, and others, along with their underlying mechanisms. The outcomes of some studies that used such inducing agents to develop AD are discussed briefly. Among chemically induced models, streptozotocin and amyloid-beta are the most frequently used, while d-galactose, scopolamine, and aluminium-induced models are being used because they are non-invasive, reproducible, and compatible. However, none of the chemical/drug-induced models fully capture the scope of AD pathology and cognitive impairment. Overall, further research is necessary to establish the stability of the models in terms of consistency and reproducibility.

Organic anion-transporting polypeptides (OATPs) play a crucial role in the transport of bile acids and bilirubin. In our previous study, interleukin 6 (IL-6) reduced OATP1B3 levels in cholestatic disease. However, it remains unclear whether IL-6 inhibits OATP1B1 expression in cholestatic diseases. This study aimed to investigate whether IL-6 can inhibit OATP1B1 expression and explore the underlying mechanisms.

The effect of stimulator of interferon genes (STING) signaling on inflammatory factors was investigated in a cholestatic mouse model using RT-qPCR and enzyme-linked immunosorbent assay. To assess the impact of inflammatory factors on OATP1B1 expression in hepatocellular carcinoma, we analyzed OATP1B1 expression by RT-qPCR and Western Blot after treating PLC/PRF/5 cells with TNF-α, IL-1β, and IL-6. To elucidate the mechanism by which IL-6 inhibits OATP1B1 expression, we examined the expression of the OATP1B1 regulator TCF4 in PLC/PRF/5 and HepG2 cells using RT-qPCR and Western Blot. The interaction mechanism between β-catenin/TCF4 and OATP1B1 was investigated by knocking down β-catenin/TCF4 through siRNA transfection.

The STING inhibitor decreased inflammatory factor levels in the cholestatic mouse model, with IL-6 exhibiting the most potent inhibitory effect on OATP1B1. IL-6 downregulated β-catenin/TCF4, leading to decreased OATP1B1 expression. Knocking-down β-catenin/TCF4 counteracted the β-catenin/TCF4-mediated repression of OATP1B1.

STING-mediated IL-6 up-regulation may inhibit OATP1B1, leading to reduced transport of bile acids and bilirubin by OATP1B1. This may contribute to altered pharmacokinetics in patients with diseases associated with increased IL-6 production.

Bile acids are byproducts of cholesterol metabolism in the liver and constitute the primary components of bile. Disruption of bile flow leads to cholestasis, characterized by the accumulation of hydrophobic bile acids in the liver and bloodstream. Such accumulation can exacerbate liver impairment. This review discussed recent developments in understanding how bile acids contribute to liver damage, including disturbances in mitochondrial function, endoplasmic reticulum stress, inflammation, and autophagy dysfunction. Mitochondria play a pivotal role in cholestatic liver injury by influencing hepatocyte apoptosis and inflammation. Recent findings linking bile acids to liver damage highlight new potential treatment targets for cholestatic liver injury.

The activation of the Kirsten RAS (KRAS) oncogene is one of the factors responsible for the transition from intermediate adenoma to carcinoma in the colon. Approximately 30% to 60% of mutations in colorectal cancer (CRC) occur in the hotspot codons 12 and 13 of exon 1 and codon 61 of exon 2. This study aimed to characterize mutations of the KRAS gene among Filipinos with CRC.

Paired frozen normal and tumor tissues from 35 CRC patients who underwent surgical resection were included. Genomic DNA was extracted, and all five coding exons were amplified by polymerase chain reaction, followed by mutation screening using denaturing high-performance liquid chromatography and DNA sequencing.

From sequencing, 18/35 (51%) samples showed mutations in exon 1 (A11R, G13C, L19W, and silent mutation L23), exon 2 (D54H), and codon 4B (silent mutation D173). Nine mutations could be considered pathogenic as they occurred within the conserved region, potentially contributing to the oncogenic potential of KRAS. Eight of these mutations were also found outside the hotspot region of the KRAS gene. Mutations were significantly associated with tumor stage III (p = 0.007) but not with other clinical parameters or survival.

This study characterizes KRAS mutations in Filipino patients with CRC, suggesting a possible difference in their cancer genetic profiles. Additionally, the use of easily accessible mutation screening techniques, such as denaturing high-performance liquid chromatography, may help increase reports of mutational profiles in Southeast Asian populations.

Type 1 bipolar disorder (BP) is a mental illness characterized by extreme shifts in mood, oscillating between manic and depressive episodes. It ranks as the sixth most prevalent psychiatric disorder globally, often emerging in the teenage years. This study aimed to identify associations between BP and 15 insertion/deletion (Indel) polymorphisms in the human genome, examining genes including TPA, UCP2, HLA-G, FADS2, ADRA2B, VEGF, PDCD6IP, SLC6A4, TLR2, APOB, TP53, LRPAP1, DHFR, MDM2, and DBH.

This case-control study involved 226 patients with BP and 235 healthy controls. Allele frequencies for each polymorphism in cases and controls were estimated using pooled samples. Polymerase chain reaction was performed for each Indel polymorphism using pooled samples as templates to estimate allele frequencies.

The data presented herein demonstrate a significant association between a 14bp Ins/Del polymorphism in the HLA-G gene and the risk of BP. The deletion allele of this polymorphism increased the risk of BP (odds ratio = 1.434, 95% confidence interval = 1.106–1.859, p = 0.007). Other 14 Indel polymorphisms were not associated with the risk of BP.

The HLA-G 14bp Indel polymorphism exhibits a significant correlation with the risk of BP in this study. This finding contributes to understanding the etiology of BP.

High-throughput proteomics has become an exciting field and a potential frontier of modern medicine since the early 2000s. While significant progress has been made in the technical aspects of the field, translating proteomics to clinical applications has been challenging. This review summarizes recent advances in clinical applications of high-throughput proteomics and discusses the associated challenges, advantages, and future directions. We focus on research progress and clinical applications of high-throughput proteomics in breast cancer, bladder cancer, laryngeal squamous cell carcinoma, gastric cancer, colorectal cancer, and coronavirus disease 2019. The future application of high-throughput proteomics will face challenges such as varying protein properties, limitations of statistical modeling, technical and logistical difficulties in data deposition, integration, and harmonization, as well as regulatory requirements for clinical validation and considerations. However, there are several noteworthy advantages of high-throughput proteomics, including the identification of novel global protein networks, the discovery of new proteins, and the synergistic incorporation with other omic data. We look forward to participating in and embracing future advances in high-throughput proteomics, such as proteomics-based single-cell biology and its clinical applications, individualized proteomics, pathology informatics, digital pathology, and deep learning models for high-throughput proteomics. Several new proteomic technologies are noteworthy, including data-independent acquisition mass spectrometry, nanopore-based proteomics, 4-D proteomics, and secondary ion mass spectrometry. In summary, we believe high-throughput proteomics will drastically shift the paradigm of translational research, clinical practice, and public health in the near future.

Both alcohol-associated liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease are leading contributors to chronic liver diseases. These conditions often coexist, exacerbating disease progression. Despite ALD being a leading cause of liver transplantation, many individuals with alcohol use disorder (AUD) do not receive treatment. In this review, we discussed the epidemiology of ALD in AUD, various treatment options for AUD, and their efficacy on liver health. Our critical analysis of current evidence underscores the need for integrated models involving multiple stakeholders to improve ALD management.

The liver plays a crucial role in maintaining whole-body homeostasis in both health and disease, engaging in important communication with other organs. The coordination of multiple signaling pathways is essential for facilitating such interorgan communication. Among these pathways, the transforming growth factor-β (TGF-β) and HIPPO signaling pathways serve critical functions as tumor suppressors, exerting pivotal control over liver development, size, and tissue regeneration. In the normal hepatic context, these pathways exhibit significant crosstalk through various molecular mechanisms. This interaction is context-dependent within the hepatic microenvironment, regulating diverse cellular processes from development to adulthood. Disruptions in the regulation of these pathways and their crosstalk contribute to the onset of liver diseases. This review delves into the intricate interplay between the canonical pathways of TGF-β and HIPPO, exploring their involvement in liver development and various pathologies such as fibrosis, cirrhosis, and tumorigenesis. Special attention is given to their impact on the epithelial-to-mesenchymal transition process, a crucial element associated with liver wound healing and cancer metastasis. By addressing these molecular interactions, the review aimed to provide insights into the underlying mechanisms that influence liver physiology and pathology, offering potential avenues for therapeutic interventions.

Idiopathic pulmonary fibrosis is a chronic, progressive, incurable lung disease, leading to irreversible lung tissue remodeling. The Notch signaling pathway, essential for lung development, has gained attention for its role in pulmonary fibrosis. While Notch1 and Notch3 have been extensively studied, the involvement of other Notch receptors, especially Notch4, remains less explored. This study aimed to evaluate the impact of Notch4 on lung fibroblast activation and its potential interaction with the transforming growth factor-beta 1 (TGFβ1) signaling.

Primary human lung fibroblasts were transduced with lentivirus containing the intracellular domain of NOTCH4 (N4ICD). Changes in gene expression in transduced cells were assessed using real-time polymerase chain reaction, immunofluorescence staining, and Western blotting. Transcriptomic analysis was also performed on N4ICD-transduced lung fibroblasts.

N4ICD overexpression significantly upregulated key fibrotic markers such as ACTA2 and COL1A1. It also induced the TGFβ1 pathway, as evidenced by SMAD2 phosphorylation and elevated TGFβ1 mRNA level. Transcriptomic analysis revealed that N4ICD-induced cells exhibited characteristics of highly invasive myofibroblasts.

This study establishes Notch4 as a novel contributor to pulmonary fibrosis, by demonstrating its ability to induce myofibroblast differentiation and interact with the TGFβ1 pathway.

Acute pancreatitis is an unpredictable and potentially lethal disease, causing tremendous pain in patients. The initial treatment of acute pancreatitis in modern medicine is supportive, but it is generally ineffective in relieving abdominal pain and distension. Traditional Chinese medicine has been shown to be more effective in regulating the body's homeostasis and reducing the clinical symptoms of pancreatitis. Yi-Dan ointment, derived from Dahuang-Mudan Decoction, is an effective external ointment for treating acute pancreatitis. The aim of this trial is to investigate the clinical efficacy of Yi-Dan ointment, providing a valuable complement to existing treatment options for pancreatitis.

This is a randomized controlled clinical trial with two parallel groups. Patients in the control group were given basic treatment and nursing for 7 days; in the treatment group, Yi-Dan ointment was applied externally in addition to basic treatment and nursing. The main indicator is the overall efficacy, serum amylase, acute physiology and chronic health evaluation Ⅱ score, symptom score, inflammatory markers, and classification of computed tomography.

The trial results will provide high-quality evidence for Yi-Dan ointment, and provide a complement to existing treatment options for pancreatitis.

The years 2019–2021 of the twenty-first century are synonymous with the COVID era, as the Coronavirus disease 2019 (COVID-19) wreaked havoc and continues to be aggressively persecuted. Globally, about 300 million COVID-19 cases and nearly 5.3 million fatalities have been recorded so far. Since then, the coronavirus RNA genome has rapidly mutated, giving rise to several mutant and recombinant variants. On March 9, 2022, a new recombinant known as Deltacron/Delmicron emerged due to inter-lineage recombination between Delta and Omicron. Many researchers consider it a “grey rhino” occurrence rather than a “black swan” event. However, some groups of scientists claim it is a “laboratory error”. Another COVID-19 variant, XE (a recombination of BA.1 and BA.2), has been discovered, which has a transmission rate ten times higher than the fastest-spreading Omicron subvariant BA.2. Delta and Omicron, two of the most novel strains, co-circulated for many weeks in several parts of the globe, allowing for coinfections and eventual recombination. Consequently, the recombinant strains XD and XF are associated with a very high transmission rate and reduced neutralizing antibody response. Under these circumstances, researchers are rushing to develop a vaccine with high efficacy against the circulating mutants and the variants likely to emerge in the near future. This review article provides recent updates on newly identified sub-variants of Omicron with an in-depth focus on their genomic alterations, infectivity patterns, and pathogenic manifestations.

Experimental models using 2/3 partial hepatectomy or chemical injury have helped identify the pathways associated with liver regeneration (LR). Several microRNAs (miRNAs) have been identified as modulators of LR, but the molecular mechanisms underlying their activity are still unclear. Given the development of new therapies targeting miRNAs, this is an important question to address. This review discusses recent studies exploring the molecular mechanisms of miRNA-dependent regulation of LR. In particular, the finding that circ-RBM23 promotes LR by sequestering cytoplasmic miRNA139-5p has furthered the understanding of the molecular mechanisms underlying circRNA activity. Interestingly, although miRNAs are generally considered negative regulators of their target mRNAs, miRNAs182-5p promotes LR by upregulating Cyp7a. Furthermore, mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) were shown to enhance LR after 2/3 partial hepatectomy by releasing miRNAs that inhibit gene expression to promote an anti-inflammatory response or miRNA-regulatory factors. Since the administration of MSCs-EVs has no hepatotoxic side effects, this may represent a therapeutic strategy to promote LR. miRNAs also mediate LR after chemical injury. This is the case for miR194 and miR21, whose downregulation activates pro-regeneration pathways to ameliorate acetaminophen-induced liver injury. In addition, the downregulation of miR21 has been shown to improve autophagy and haemostasis after acetaminophen overdose. Although further studies are needed to improve their efficacy as therapeutics, the evidence gathered in this review has led to a better understanding of the molecular mechanisms associated with the control of LR by miRNAs.

Non-alcoholic fatty liver disease (NAFLD) is a kind of metabolic disorder characterized by excessive fat deposition in the liver and ranging from simple steatosis (simple NAFLD) to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma [1]. It has recently been increasing annually; for example, it was recently estimated to have a global prevalence of 32.4%, which seriously threatens human health [2]. Thus, the discovery of new therapeutic targets is of great importance because there is no specified drug for the treatment of NAFLD. On the other hand, the pathogenesis of NAFLD is complicated and still unclear. Recent studies have proposed ferroptosis as related to the disease progressions of NAFLD. Preliminary evidence indicated that ferroptosis in hepatocytes and hepatic macrophages could induce NASH and that complex regulatory mechanisms were involved. In the future, inhibition of ferroptosis may hopefully become an emerging target in treating NAFLD.

The world has entered an aging society, and it is expected that the global population aged 60 years or older will reach 1.5 billion by 2035. Aging is gradually becoming a major public health issue, posing a significant challenge to healthcare systems. It is a complex natural physiological process involving the irreversible degeneration of body cells, tissues, and organs, and it is a major risk factor for many chronic diseases.

Patients with corona virus disease 2019 (COVID-19) face not only physical strains but also significant psychological stress, highlighting the importance of addressing their mental health concerns. This study aimed to evaluate the impact of Lianhua Qingwen on the psychological well-being of asymptomatic and mildly symptomatic COVID-19 patients, providing empirical evidence to guide clinical practices.

Conducted in eight shelter hospitals in Shanghai, the study employed a cluster randomization method to allocate patients equally into either the Lianhua Qingwen group or the control group. The Lianhua Qingwen group received oral doses of four capsules or one packet of granules three times daily for 14 days. In contrast, the control group received standardized treatment according to the diagnostic and treatment plan, excluding Lianhua Qingwen. Mental health was assessed using the Self-rating Depression Scale and Self-rating Anxiety Scale, with symptom reporting on the 7th and 14th days, accompanied by nucleic acid test result screenshots. A follow-up investigation on new disease occurrence was conducted six months post-discharge.

Among the 2,652 valid questionnaire respondents, the Lianhua Qingwen group accounted for 1,665 cases, characterized by a higher proportion of females (32.7% vs. 26.9%), younger age (44.8 vs. 46.2 years), lower percentages of asymptomatic infections (27.6% vs. 38.5%), higher baseline Patient Health Questionnaire-9 scores (2.7 vs. 1.9), and higher Generalized Anxiety Disorder 7 scores (1.9 vs. 1.4). Further multivariate logistic regression analysis explored factors influencing the alleviation of depressive and anxiety symptoms during follow-up, revealing that Lianhua Qingwen use was an independent factor in reducing anxiety (odds ratio = 1.37, 95% confidence interval 1.14–1.65, p = 0.001) and depression (odds ratio = 1.42, 95% confidence interval 1.19–1.69, p < 0.0001). Lianhua Qingwen increased the likelihood of reducing anxiety by 37% and depression by 42%.

Lianhua Qingwen significantly alleviated anxiety and depression symptoms in COVID-19 patients, suggesting its potential therapeutic efficacy in mitigating these conditions.

Fuzi, the processed product of daughter roots of Aconitum carmichaelii Debx., is a well-known Chinese medicine for the treatment of heart failure (HF) and related cardiac diseases. This study aimed to investigate the molecular mechanism of the cardioprotective effects of Fuzi water decoction (FWD) and Fuzi water-soluble alkaloids (FWA) on the model of HF.

The HF model of rats was prepared through intravenous injection of propafenone hydrochloride. The normal group, model group, FWD-treated groups (1.25 g/kg, 2.5 g/kg, 5 g/kg) and positive group (Shenfu Injection, 3.3 mL/kg) were set up. Heart rate, LV+dp/dtmax, and LV-dp/dtmax were recorded at 5 m, 10 m, 20 m, 30 m, and 60 m after drug administration, respectively. The contents of atrial natriuretic peptide, brain natriuretic peptide (BNP), angiotensin II, and aldosterone in serum were determined 20 m post-administration. An in vitro cardiomyocyte hypertrophy model with HDAC2 overexpression was constructed and verified by lentivirus transfection. The experiment included a blank group, FWD-treated groups (3 mg/mL, 1.5 mg/mL), and FWA-treated groups (4 mg/mL, 2 mg/mL). For transcriptome analysis, the model group, blank group, and FWD-treated group (2.5 g/kg) at 20 m and 60 m in vivo, and different dose groups in vitro, were selected to analyze the therapeutic mechanisms of FWD and FWA.

All FWD treatment groups showed an increased heart rate, among which the groups with 2.5 g/kg and 5 g/kg FWD showed better effects, significantly increasing LV+dp/dtmax and LV-dp/dtmax after 20 m of administration and significantly reducing BNP and aldosterone serum levels. In the constructed cardiomyocyte hypertrophy model, HDAC2 expression, atrial natriuretic peptide and BNP protein levels, and cell surface area increased. Transcriptome data from both in vivo and in vitro showed that FWD and FWA could exert cardioprotective effects through pathways such as the PI3K-Akt signaling pathway, NF-κB signaling pathway, and ATP-binding cassette (ABC) transporters, involving key genes such as ITGB1, TLR2, and CDKN1A. Fuzi inhibited the hypertrophic gene HDAC2. Additionally, based on weighted gene co-expression network analysis, ABC transporters may be an important molecular pathway for FWA in treating HF.

Both FWD and FWA can ameliorate HF by regulating apoptosis, proliferation, and anti-fibrosis, with ABC transporters potentially being the main pathway for the action of FWA.

Gut dysbiosis and abnormal cytokine profiles are common in cirrhosis. This study aimed to evaluate the correlations between them.

In the blood plasma of cirrhosis patients and controls, 27 cytokines were examined using a multiplex assay. The plasma levels of nitrites (stable metabolites of the endothelial dysfunction biomarker nitric oxide) and lipopolysaccharide (LPS) were examined. The fecal microbiota was assessed by 16S rRNA gene sequencing.

Levels of IL-1b, IL-2, IL-6, IL-13, IP-10, IFN-g, TNF-a, LPS, and nitrites were higher in cirrhosis patients than in controls, while levels of IL-4, IL-7, and PDGF-BB were lower. The LPS level was directly correlated with the levels of IL-1b, IL1-Ra, IL-9, IL-17, PDGF-BB, IL-6, TNF-a, and nitrites. The nitrite level was significantly directly correlated with the levels of TNF-a, GM-CSF, IL-17, and IL-12, and inversely correlated with the IL-7 level. TNF-a levels were directly correlated with ascites severity and the abundance of Negativicutes, Enterobacteriaceae, Veillonellaceae, and Klebsiella, while inversely correlated with the abundance of Firmicutes, Clostridia, and Subdoligranulum. IFN-g levels were directly correlated with the abundance of Bacteroidaceae, Lactobacillaceae, Bacteroides, and Megasphaera, and inversely correlated with the abundance of Verrucomicrobiota, Akkermansiaceae, Coriobacteriaceae, Akkermansia, Collinsella, and Gemella. IL-1b levels were directly correlated with the abundance of Comamonadaceae and Enterobacteriaceae and inversely correlated with the abundance of Marinifilaceae and Dialister. IL-6 levels were directly correlated with the abundance of Enterobacteriaceae, hepatic encephalopathy, and ascites severity, and inversely correlated with the abundance of Peptostreptococcaceae, Streptococcaceae, and Streptococcus.

The abundance of harmful gut microbiota taxa and endotoxinemia directly correlates with the levels of proinflammatory cytokines.