Bloodstream Coinfections and Antimicrobial Resistance in Hospitalized COVID-19 Patients: A Single-center Retrospective Study.

BACKGROUND/AIM: Bloodstream infections in patients with COVID-19 are linked to higher mortality rates, whilst data on epidemiology and resistance patterns remains scarce to guide management and prevent antibiotic resistance. This research focuses on the prevalence, clinical features, causative microorganisms, and antimicrobial susceptibility of bacterial and fungal secondary bloodstream co-infections in hospitalized patients with COVID-19. PATIENTS AND METHODS: In this retrospective study analysis of 230 patients with COVID-19 from Central Taiwan (June 2021 to June 2022), pathogens were identified via MALDI-TOF MS and Vitek 2 system with Clinical & Laboratory Standards Institute (CLSI) standards. RESULTS: In the cohort, 17.8% experienced bloodstream infections, resulting in a total of 45 isolates from the 41 bloodstream infection patients: predominantly gram-positive bacteria (Staphylococcus and Enterococcus) at 69%, gram-negative at 29% (Escherichia coli and Klebsiella pneumoniae), and fungi at 2%. Infected patients showed significantly elevated levels of white blood count (WBC), C-reactive protein (CRP) and procalcitonin (PCT). Of note, resistance to common antibiotics, such as fluoroquinolones, cephalosporins, and oxacillin was significant, especially in K. pneumoniae, Acinetobacter species, and S. aureus infections. CONCLUSION: Our study highlights the influence of bacterial infections in hospitalized patients with COVID-19. The bacterial infections were discovered to impact the clinical trajectory of COVID-19, potentially exacerbating or mitigating its symptoms, severity and fatality. These insights are pivotal to addressing clinical challenges in COVID-19 management and underscoring the need for tailored medical interventions. Understanding these co-infections is thus essential for optimizing patient care and improving overall outcomes in the post COVID-19 pandemic era.

Mucinous cystadenocarcinoma of the breast harbours TRPS1 expressions and PIK3CA alterations.

AIMS: Breast mucinous cystadenocarcinoma (BMCA) is a rare tumour recently recognised as a distinct entity by the World Health Organisation Tumour Classification Series. BMCA is a triple-negative tumour that lacks specific immunohistochemical markers; therefore, distinguishing it from mimickers such as ovarian and pancreatic cystadenocarcinomas requires careful clinicopathological correlation. Due to its rarity, little is known about the molecular alterations that underlie BMCA. METHODS AND RESULTS: In this study, we used immunohistochemical staining methods to investigate TRPS1 (trichorhinophalangeal syndrome type 1) expression in BMCA and compare it to expression in ovarian and pancreatic mucinous cystadenocarcinomas. We also collected tumour samples from three BMCA patients for molecular analysis by MALDI-TOF mass spectrometry, real-time polymerase chain reaction, whole exome sequencing and fluorescence in-situ hybridisation. TRPS1 immunoreactivity was found only in BMCA tumour cells and not in the ovarian and pancreatic counterparts. One of the three BMCA tumours also showed a PIK3CA hot-spot mutation, which was confirmed by whole genome next-generation sequencing (NGS). No KRAS, NRAS, BRAF or AKT mutations were found. CONCLUSIONS: To our knowledge, this is the first demonstration of TRPS1 expression in BMCA patients and the first identification of a PIK3CA hotspot mutation in these tumours. These findings provide insights into the molecular mechanisms underlying BMCA tumorigenesis and suggest a potential drug target for this rare and poorly understood cancer.

High G9a Expression in DLBCL and Its Inhibition by Niclosamide to Induce Autophagy as a Therapeutic Approach.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a malignant lymphoid tumor disease that is characterized by heterogeneity, but current treatment does not benefit all patients, which highlights the need to identify oncogenic genes and appropriate drugs. G9a is a histone methyltransferase that catalyzes histone H3 lysine 9 (H3K9) methylation to regulate gene function and expression in various cancers. METHODS: TCGA and GTEx data were analyzed using the GEPIA2 platform. Cell viability under drug treatment was assessed using Alamar Blue reagent; the interaction between G9a and niclosamide was assessed using molecular docking analysis; mRNA and protein expression were quantified in DLBCL cell lines. Finally, G9a expression was quantified in 39 DLBCL patient samples. RESULTS: The TCGA database analysis revealed higher G9a mRNA expression in DLBCL compared to normal tissues. Niclosamide inhibited DLBCL cell line proliferation in a time- and dose-dependent manner, reducing G9a expression and increasing p62, BECN1, and LC3 gene expression by autophagy pathway regulation. There was a correlation between G9a expression in DLBCL samples and clinical data, showing that advanced cancer stages exhibited a higher proportion of G9a-expressing cells. CONCLUSION: G9a overexpression is associated with tumor progression in DLBCL. Niclosamide effectively inhibits DLBCL growth by reducing G9a expression via the cellular autophagy pathway; therefore, G9a is a potential molecular target for the development of therapeutic strategies for DLBCL.

Emodin Ameliorates the Efficacy of Carfilzomib in Multiple Myeloma Cells via Apoptosis and Autophagy.

BACKGROUND: Carfilzomib, the proteasome inhibitor, can increase the overall survival rate of multiple myeloma (MM) patients undergoing targeted therapy. However, relapse and toxicity present great challenges for such treatment, so an urgent need for effective combination therapy is necessary. Emodin is a natural chemical compound that inhibits the proliferation of various cancers and can effectively combine with other treatments. In this study, we evaluated the sensitizing effect of emodin combined with carfilzomib on MM cells. METHODS: The cells were treated with emodin, carfilzomib, and a combination of drugs to determine their effects on cell proliferation and viability. The cell cycle distribution and reactive oxygen species (ROS) expression were measured by flow cytometry. The level of RNA and protein were analyzed through real-time qPCR and immunoblotting. RESULTS: Emodin acted synergistically with carfilzomib to reduce the proliferation and viability of MM cell lines in vitro. Furthermore, the combination of emodin and carfilzomib increased ROS production, inducing apoptosis and autophagy pathways via caspase-3, PARP, p62, and LC3B. CONCLUSIONS: These results provide a molecular target for combination therapy in MM patients.

Glycyrrhiza uralensis root extract ameliorates high glucose-induced renal proximal tubular fibrosis by attenuating tubular epithelial-myofibroblast transdifferentiation by targeting TGF-ß1/Smad/Stat3 pathway.

Growing evidences indicate that high glucose toxicity-associated fibrotic effects play a pivotal role in diabetic nephropathy (DN). Tubular epithelial-myofibroblast transdifferentiation is a major hallmark of renal fibrosis event under diabetic stress. Roots of Glycyrrhiza uralensis (Radix glycyrrhizae) used as a sweetener and traditional Chinese medicine possess high potential for renal protection. In this study, a cell model for high glucose (HG) injury with HK-2 renal proximal tubular epithelial cell line and a type-II-diabetes model with Apoeem1/Narl /Narl mice was established and the beneficial effects of aqueous R. glycyrrhizae extract (RGE) was investigated. RGE-induced regulation on the high glucose-induced excessive production of TGF-ß1 and the Smad/Stat3 mechanisms of renal fibrosis were determined. HK-2 cells were challenged with 45 mM of high glucose for 48 hr. Following high glucose challenge, the cells were treated with 0.5, 1, and 1.5 mg/ml concentrations of RGE. The effect of RGE on DN was determined using high fructose diet-induced type-II-diabetes in Apoeem1/Narl /Narl mice models. Our results showed that RGE suppressed the expression of HG-induced TGFß signaling and associated fibrosis mechanism better than the pharmacological drug acarbose. These data suggest that RGE as a potential herbal supplement in attenuating fibrosis-associated diabetic nephropathy and a potential agent in diabetes treatments.

IGF IIRα-triggered pathological manifestations in the heart aggravate renal inflammation in STZ-induced type-I diabetes rats.

Pathological manifestations in either heart or kidney impact the function of the other and form the basis for the development of cardiorenal syndrome. However, the mechanism or factors involved in such scenario are not completely elucidated. In our study, to find the correlation between late fetal gene expression in diabetic hearts and their influence on diabetic nephropathy, we created a rat model with cardiac specific overexpression of IGF-IIRα, which is an alternative splicing variant of IGFIIR, expressed in pathological hearts. In this study, transgenic rats over expressing cardiac specific IGF-IIRα and non-transgenic animal models established in SD rats were administered with single dose of streptozotocin (STZ, 55 mg/Kg) to induce Type I diabetes. The correlation between IGF-IIRα and kidney damages were further determined based on their intensity of damage in the kidneys. The results show that cardiac specific overexpression of IGF-IIRα elevates the diabetes associated inflammation and morphological changes in the kidneys. The diabetic transgenic rats showed advancement in the pathological features such a renal tubular damage, collagen accumulation and enhancement in STAT3 associated mechanism of renal fibrosis. The results therefore show that that IGF-IIRα expression in the heart during pathological condition may worsen symptoms of diabetic nephropathy in rats.

Scalars Gliding through an Expanding Universe.

In this Letter, we investigate the effects of single derivative mixing in massive bosonic fields. In the regime of large mixing, we show that this leads to striking changes of the field dynamics, delaying the onset of classical oscillations and decreasing, or even eliminating, the friction due to Hubble expansion. We highlight this phenomenon with a few examples. In the first example, we show how an axionlike particle can have its number abundance parametrically enhanced. In the second example, we demonstrate that the QCD axion can have its number abundance enhanced allowing for misalignment driven axion dark matter all the way down to f_{a} of order astrophysical bounds. In the third example, we show that the delayed oscillation of the scalar field can also sustain a period of inflation. In the last example, we present a situation where an oscillating scalar field is completely frictionless and does not dilute away in time.

Characterization of in vitro and in vivo bioactivity of a ferulic acid-2-Hydroxypropyl-ß-cyclodextrin inclusion complex.

Ferulic acid (FA) belongs to the family of phenolic acids and exhibits a wide variety of biological activities. However, the bioavailability of FA is not optimal, owing to its limited aqueous solubility. Several methods have been developed to increase FA bioavailability and enhance its cytoprotective effects. Complexing FA with cyclodextrins (CDs) may provide an alternative method to approach these goals. In this study, we prepared an FA-2-hydroxypropyl-ß-CD (FA-HP-ß-CD) complex, at a 1:1 M ratio of FA to HP-ß-CD, which was characterized by 1H NMR, two-dimensional rotating frame spectroscopy and differential scanning calorimetry. Aqueous solubility of FA was improved after complexing with HP-ß-CD. Furthermore, in vitro and in vivo experimental results indicated that the FA-HP-ß-CD complex had greater bioactivity than FA alone. Therefore, we can conclude that the limitations of FA usage due to low aqueous solubility and bioavailability can be overcome by creating an HP-ß-CD inclusion complex with the hydrophobic FA.

The effects of laser acupuncture on the modulation of cartilage extracellular matrix macromolecules in rats with adjuvant-induced arthritis.

OBJECTIVES: Articular cartilage damage related to irreversible physical disability affects most patients with chronic rheumatoid arthritis (RA). Strategies targeting the preservation of cartilage function are needed. Laser acupuncture (LA) can be an emerging alternative therapy for RA; however, its molecular mechanism underlying the beneficial effect on cartilage has not been elucidated. This study aimed to examine the potential chondroprotective effects of LA on extracellular matrix (ECM) macromolecules and proinflammatory cytokines in the articular cartilage of adjuvant-induced arthritis (AIA) rats and explore its related mechanisms. DESIGN: Monoarthritis was induced in adult male Sprague-Dawley rats (250-300 g) via intraarticular injection of complete Freund's adjuvant (CFA) into the tibiotarsal joint. Animals were treated with LA at BL60 and KI3 acupoints three days after CFA administration with a 780 nm GaAlAs laser at 15 J/cm2 daily for ten days. The main outcome measures including paw circumference, paw withdrawal threshold, histopathology and immunoassays of tumor necrosis factor-α (TNF-α), collagen type II (CoII), cartilage oligomeric matrix protein (COMP) were analyzed. RESULTS: LA significantly reduced ankle edema and inflammation-induced hyperalgesia in AIA rats (P < 0.05). Moreover, the TNF-α levels were significantly decreased while CoII, COMP and proteoglycans proteins were significantly enhanced following LA stimulation of the AIA cartilage compared to those treated with sham-LA (P < 0.05). CONCLUSIONS: LA attenuates cartilage degradation in AIA rat by suppressing TNF-α activation and up-regulating ECM macromolecules, suggesting LA might be of potential clinical interest in RA treatment.

Primordial Anisotropies in the Gravitational Wave Background from Cosmological Phase Transitions.

Phase transitions in the early Universe can readily create an observable stochastic gravitational wave background. We show that such a background necessarily contains anisotropies analogous to those of the cosmic microwave background (CMB) of photons, and that these too may be within reach of proposed gravitational wave detectors. Correlations within the gravitational wave anisotropies and their cross-correlations with the CMB can provide new insights into the mechanism underlying primordial fluctuations, such as multifield inflation, as well as reveal the existence of nonstandard "hidden sectors" of particle physics in earlier eras.

ß-Sitosterol-2-hydroxypropyl-ß-cyclodextrin inclusion complex: Characterization and inhibitory effect on adipogenesis in 3T3-L1 pre-adipocytes.

ß-Sitosterol (Sit) has been used as a functional food additive. Among its many beneficial effects, this phytosterol plays a role in controlling obesity by inhibiting the adipogenesis process of pre-adipocytes. However, the highly lipophilic character of Sit limits its bioavailability. In the present study, 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) was used to form a complex with Sit, namely the Sit-HP-ß-CD inclusion complex, and the inhibitory effect of this complex on adipogenesis in the 3T3-L1 pre-adipocyte cell line was investigated. The results of DSC, TLC, 1H NMR spectroscopy, and 2D ROESY showed that the Sit-HP-ß-CD inclusion complex was successfully synthesized. In addition, the inhibitory effect of the Sit-HP-ß-CD inclusion complex on adipogenesis was evaluated using the Oil Red O staining method and western blot analysis after a 14-day adipogenesis induction in 3T3-L1 pre-adipocytes. The results showed that the Sit-HP-ß-CD inclusion complex had a higher efficiency than Sit in reducing intracellular lipid accumulation and the expression levels of PPARγ and FAS in 3T3-L1 cells, suggesting that the inhibitory effect on adipogenesis was improved by the formation of the Sit and HP-ß-CD complex.

A novel sol-gel-derived calcium silicate cement with short setting time for application in endodontic repair of perforations.

Mineral trioxide aggregate (MTA) is the most frequently used repair material in endodontics, but the long setting time and reduced mechanical strength in acidic environments are major shortcomings. In this study, a novel sol-gel-derived calcium silicate cement (sCSC) was developed using an initial Ca/Si molar ratio of 3, with the most effective mixing orders of reactants and optimal HNO3 catalyst volumes. A Fourier transform infrared spectrometer, scanning electron microscope with energy-dispersive X-ray spectroscopy, and X-ray powder diffractometer were used for material characterization. The setting time, compressive strength, and microhardness of sCSC after hydration in neutral and pH 5 environments were compared with that of MTA. Results showed that sCSC demonstrated porous microstructures with a setting time of ~30 min, and the major components of sCSC were tricalcium silicate, dicalcium silicate, and calcium oxide. The optimal formula of sCSC was sn200, which exhibited significantly higher compressive strength and microhardness than MTA, irrespective of neutral or pH 5 environments. In addition, both sn200 and MTA demonstrated good biocompatibility because cell viability was similar to that of the control. These findings suggest that sn200 merits further clinical study for potential application in endodontic repair of perforations.

A water-based topical Chinese traditional medicine (Zicao) for wound healing developed using 2-hydroxypropyl-ß-cyclodextrin.

Zicao is a traditional Chinese herbal medicine that has been used for the topical treatment of wounds in the form of oil-based ointment for several hundred years. To overcome the disadvantages of oil-based ointment such as irritation, discomfort, and difficulty in cleaning, this study developed a water-based topical formulation of Zicao. An ethanol extract of Zicao was included in 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) to form a water-soluble Zicao-HP-ß-CD complex. The formation of the Zicao-HP-ß-CD complex was determined using LC-MS, 1H NMR, ROSEY, and solubility analysis. The bioactivity of Zicao-HP-ß-CD complex in aqueous solution was evaluated using cellular uptake in vitro and experimental excision wounds in vivo. The LC-MS, 1H NMR, ROESY, and solubility analyses results show that Zicao extract was successfully included by the HP-ß-CD. The results of the cellular uptake in vitro and wound healing in vivo suggest that the effect of Zicao was enhanced following the formation of the Zicao-HP-ß-CD complex. Therefore, we concluded that complexation with HP-ß-CD might provide a potential method for developing an effective water-based topical solution of Zicao.

San Huang Shel Shin Tang beta-cyclodextrin complex augmented the hepatoprotective effects against carbon tetrachloride-induced acute hepatotoxicity in rats.

BACKGROUND: San Huang Shel Shin Tang (SHSST) is a traditional herbal decoction used as a hepato-protective agent and is composed of Rheum officinale Baill, Scutellaria baicalnsis Geprgi and Coptis chinensis Franch (2:1:1 w/w). Beta-cyclodextrin (ß-CD) modification may potentially increase the solubility and spectral properties of SHSST. METHODS: In this research, the hepato-protective effects of unmodified SHSST, ß-CD modified SHSST complex (SHSSTc) and silymarin were evaluated in carbon tetrachloride (CCl4) induced acute hepatotoxicity in rats. RESULTS: SHHSTc (40 mg/kg/day) and silymarin (100 mg/kg/day) both decreased the CCl4-induced cirrhosis pathway-related transforming growth factor beta (TGF-ß) and apoptosis pathway-related caspase-8 protein expressions, but SHSST (40 mg/kg/day) did not reduce TGF-ß and caspase-8 significantly . Moreover, SHHSTc (40 mg/kg/day) enhanced the activation of insulin-like growth factor 1 receptor (IGF1R) mediated survival pathway than the silymarin (100 mg/kg/day) to protect the liver from damage induced by CCl4. CONCLUSIONS: ß-CD modification promotes hepato-protective effects of SHSST and reduces the required-dosage of the SHSST.

Fabrication of Silica-Coated Hollow Carbon Nanospheres Encapsulating Fe3O4 Cluster for Magnetical and MR Imaging Guided NIR Light Triggering Hyperthermia and Ultrasound Imaging.

Iron oxide nanoparticles (IONPs)-carbon (C) hybrid zero-dimensional nanostructures normally can be categorized into core-shell and yolk-shell architectures. Although IONP-C is a promising theranostic nanoagent, the in vivo study has surprisingly been less described. In addition, little effort has strived toward the fabrication of yolk-shell compared to the core-shell structures. In this context, we synthesized a yolk-shell type of the silica-coated hollow carbon nanospheres encapsulating IONPs cluster, which can be dispersed in aqueous solution for systemic studies in vivo, via the preparation involving the mixed micellization, polymerization/hollowing, sol-gel (hydration-condensation), and pyrolysis processes. Through a surface modification of the polyethylenimine followed by the sol-gel process, the silica shell coating was able to escape from condensing and sintering courses resulting in aggregation, due to the annealing. Not limited to the well-known functionalities in magnetical targeting and magnetic resonance (MR) imaging for IONP-C hybrid structures, we expanded this yolk-shell NPs as a near-infrared (NIR) light-responsive echogenic nanoagent giving an enhanced ultrasound imaging. Overall, we fabricated the NIR sensitive yolk-shell IONP-C to activate ultrasound imaging and photothermal ablation under magnetically and MR imaging guided therapy.

Hypoxia Augments Increased HIF-1α and Reduced Survival Protein p-Akt in Gelsolin (GSN)-Dependent Cardiomyoblast Cell Apoptosis.

Cytoskeleton filaments play an important role in cellular functions such as maintaining cell shape, cell motility, intracellular transport, and cell division. Actin-binding proteins (ABPs) have numerous functions including regulation of actin filament nucleation, elongation, severing, capping, cross linking, and actin monomer sequestration. Gelsolin (GSN) is one of the actin-binding proteins. Gelsolin (GSN) is one of the actin-binding proteins that regulate cell morphology, differentiation, movement, and apoptosis. GSN also regulates cell morphology, differentiation, movement, and apoptosis. In this study, we have used H9c2 cardiomyoblast cell and H9c2-GSN stable clones to understand the roles and mechanisms of GSN overexpression in hypoxia-induced cardiomyoblast cell death. The data show that hypoxia or GSN overexpression induces HIF-1α expression and reduces the expression of survival markers p-Akt and Bcl-2 in H9c2 cardiomyoblast cells. Under hypoxic conditions, GSN overexpression further reduces p-Akt expression and elevates total as well as cleaved GSN levels and HIF-1α levels. In addition, GSN overexpression enhances apoptosis in cardiomyoblasts under hypoxia. Hypoxic challenge further induced activated caspase-3 and cell death that was attenuated after GSN knock down, which implies that GSN is a critical therapeutic target against hypoxia-induced cardiomyoblast cell death.

Discovery of a novel anticancer agent with both anti-topoisomerase I and II activities in hepatocellular carcinoma SK-Hep-1 cells in vitro and in vivo: Cinnamomum verum component 2-methoxycinnamaldehyde.

Cinnamomum verum is used to make the spice cinnamon and has been used as a traditional Chinese herbal medicine for various applications. We evaluated the anticancer effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the bark of the plant, and its underlying molecular biomarkers associated with carcinogenesis in human hepatocellular carcinoma SK-Hep-1 cell line. The results show that 2-MCA suppressed proliferation and induced apoptosis as indicated by mitochondrial membrane potential loss, activation of caspase-3 and caspase-9, increase in the DNA content in sub-G1, and morphological characteristics of apoptosis, including blebbing of plasma membrane, nuclear condensation, fragmentation, apoptotic body formation, and long comet tail. In addition, 2-MCA also induced lysosomal vacuolation with increased volume of acidic compartments, suppressions of nuclear transcription factors NF-κB, cyclooxygenase-2, prostaglandin E2 (PGE2), and both topoisomerase I and II activities in a dose-dependent manner. Further study reveals the growth-inhibitory effect of 2-MCA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of 2-MCA against SK-Hep-1 cells is accompanied by downregulations of NF-κB-binding activity, inflammatory responses involving cyclooxygenase-2 and PGE2, and proliferative control involving apoptosis, both topoisomerase I and II activities, together with an upregulation of lysosomal vacuolation and volume of acidic compartments. Similar effects (including all of the above-mentioned effects) were found in other tested cell lines, including human hepatocellular carcinoma Hep 3B, lung adenocarcinoma A549, squamous cell carcinoma NCI-H520, colorectal adenocarcinoma COLO 205, and T-lymphoblastic MOLT-3 (results not shown). Our data suggest that 2-MCA could be a potential agent for anticancer therapy.

Discovery of a novel anti-cancer agent targeting both topoisomerase I and II in hepatocellular carcinoma Hep 3B cells in vitro and in vivo: Cinnamomum verum component 2-methoxycinnamaldehyde.

Cinnamomum verum has been used as a traditional Chinese herbal medicine. We evaluated the anticancer effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the bark of the plant, in hepatocellular carcinoma Hep 3B cells. The results show that 2-MCA suppressed proliferation and induced apoptosis as indicated by an up-regulation of pro-apoptotic bax and bak genes and down-regulation of anti-apoptotic bcl-2 and bcl-XL genes, mitochondrial membrane potential loss, cytochrome c release, activation of caspase 3 and 9, increase in the DNA content in sub G1, and morphological characteristics of apoptosis. 2-MCA also induced lysosomal vacuolation with increased volume of acidic compartments (VAC), suppressions of nuclear transcription factors NF-κB, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and both topoisomerase I and II activities in a dose-dependent manner. Further study reveals the growth-inhibitory effect of 2-MCA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of 2-MCA against Hep 3B cells is accompanied by downregulations of NF-κB binding activity, inflammatory responses involving COX-2 and PGE2, and proliferative control involving apoptosis, both topoisomerase I and II activities, together with an upregulation of lysosomal vacuolation and VAC. Our data suggest that 2-MCA could be a potential agent for anticancer therapy.

Anti-apoptotic effect of San Huang Shel Shin Tang cyclodextrin complex (SHSSTc) on CCl4 -induced hepatotoxicity in rats.

The metabolic loading is heavier in liver especially when injured or inflammation. San Huang Shel Shin Tang (SHSST) was an old traditional herbal decoction, which composed with Rheum officinale Baill, Scutellaria baicalnsis Geprgi and Coptis chinensis Franch (1:1:2 in weight), can provide a liver protection effects. We used a beta-cyclodextrin (ß-CD) drug modification method in reduce of the necessary dose of the SHSST. As the results, the FAS-FADD expressions leaded apoptosis in CCl4 intraperitoneal (IP) injection induced acute liver injury in rats. Silymarin, baicalein, SHSST, and SHSST ß-CD complex (SHSSTc) pretreatments protected liver through the decreasing of the expressions of FAS-FADD and downstream caspase-3 and caspase-8. Particularly, SHSSTc (30 mg/kg day) treatment enhanced cell survival pathway activation through the PI3K, Akt and Bad phosphorylation. Compared with SHSST as well as silymarin and baicalein, SHSSTc provided a magnificent liver protection effect, especially in survival pathway activation/TUNEL-apoptotic cell reduction/serum cholesterol level suppression. All these data suggested that ß-CD complex modified the SHSST and promoted the bioavailability and liver protection effects. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 663-670, 2016.