Therapeutic Peptide RF16 Derived from CXCL8 Inhibits MDA-MB-231 Cell Invasion and Metastasis.

Interleukin (IL)-8 plays a vital role in regulating inflammation and breast cancer formation by activating CXCR1/2. We previously designed an antagonist peptide, (RF16), to inhibits the activation of downstream signaling pathways by competing with IL-8 in binding to CXCR1/2, thereby inhibiting IL-8-induced chemoattractant monocyte binding. To evaluate the effect of the RF16 peptide on breast cancer progression, triple-negative MDA-MB-231 and ER-positive MCF-7 breast cancer cells were used to investigate whether RF16 can inhibit the IL-8-induced breast cancer metastasis. Using growth, proliferation, and invasiveness assays, the results revealed that RF16 reduced cell proliferation, migration, and invasiveness in MDA-MB-231 cells. The RF16 peptide also regulated the protein and mRNA expressions of epithelial-mesenchymal transition (EMT) markers in IL-8-stimulated MDA-MB-231 cells. It also inhibited downstream IL-8 signaling and the IL-8-induced inflammatory response via the mitogen-activated protein kinase (MAPK) and Phosphoinositide 3-kinase (PI3K) pathways. In the xenograft tumor mouse model, RF16 synergistically reinforces the antitumor efficacy of docetaxel by improving mouse survival and retarding tumor growth. Our results indicate that RF16 significantly inhibited IL-8-stimulated cell growth, migration, and invasion in MDA-MB-231 breast cancer cells by blocking the activation of p38 and AKT cascades. It indicated that the RF16 peptide may serve as a new supplementary drug for breast cancer.

Assessing the feasibility, acceptability and impacts of an education program on hepatitis B testing uptake among ethnic Chinese in Australia: results of a randomised controlled pilot study.

BACKGROUND: In Australia, Chinese migrants are among the populations most affected by hepatitis B virus (HBV) infection but often experience late diagnosis or access to clinical care. This study aims to explore approaches to increase HBV testing in Australia's Chinese community and inform evaluation planning, specifically to i) assess the feasibility and acceptability of HBV educational programs, and ii) compare HBV testing uptake in people receiving a tailored education resource focussing on liver cancer prevention compared with a standard HBV education package. METHODS: This is a pre-post mixed-methods pilot and feasibility study. People of Chinese ethnicity and unsure of their HBV infection or immunity status were recruited from ten community sites in Melbourne, Australia in 2019-2020. Participants were randomised to receive an education package (comprised of a leaflet and in-person one-on-one educational session) with a focus on either 1) standard HBV-related information, or 2) liver cancer prevention. Participants completed a baseline questionnaire prior to receiving the intervention and were followed up at 6 months' time for a questionnaire and an opt-in semi-structured interview. Primary study outcomes included feasibility of study procedures, measured by recruitment, participation, and retention rates; acceptability of the education program assessed by acceptability scores; and HBV testing uptake rate in each arm. Secondary outcomes include HBV-related knowledge change, assessed by pre-post comparison; and factors affecting participants' testing behaviour analysed using qualitative data. RESULTS: Fifty-four participants received an education package; baseline and follow-up data from 33 (61%) were available. The study procedures of recruitment and retention were feasible; the acceptability of the education program was moderate with improved HBV-related knowledge observed. Four participants self-reported being tested: one (1/15, 7%) in the standard HBV information group and three (3/18, 17%) in the liver cancer prevention information group. Factors identified as affecting testing included perceived relevance and seriousness of HBV, healthcare access and costs of testing, and perceptions of the role of primary care providers in HBV-related care. CONCLUSION: A tailored education program targeting ethnic Chinese in Australia was feasible with moderate acceptability. A larger study is required to determine if a liver cancer prevention message would improve HBV testing uptake in Chinese community than standard HBV education message. Supports from healthcare providers, community-based testing programs, and public health education programs are likely needed to motivate diagnostic testing among Chinese people at risk of HBV infection.

Therapeutic Effect of a Newly Isolated Lytic Bacteriophage against Multi-Drug-Resistant Cutibacterium acnes Infection in Mice.

Acne vulgaris, which is mostly associated with the colonization of Cutibacterium acnes (C. acnes), is a common skin inflammatory disease in teenagers. However, over the past few years, the disease has extended beyond childhood to chronically infect approximately 40% of adults. While antibiotics have been used for several decades to treat acne lesions, antibiotic resistance is a growing crisis; thus, finding a new therapeutic target is urgently needed. Studies have shown that phage therapy may be one alternative for treating multi-drug-resistant bacterial infections. In the present study, we successfully isolated a C. acnes phage named TCUCAP1 from the skin of healthy volunteers. Morphological analysis revealed that TCUCAP1 belongs to the family Siphoviridae with an icosahedral head and a non-contractile tail. Genome analysis found that TCUCAP1 is composed of 29,547 bp with a G+C content of 53.83% and 56 predicted open reading frames (ORFs). The ORFs were associated with phage structure, packing, host lysis, DNA metabolism, and additional functions. Phage treatments applied to mice with multi-drug-resistant (MDR) C.-acnes-induced skin inflammation resulted in a significant decrease in inflammatory lesions. In addition, our attempt to formulate the phage into hydroxyethyl cellulose (HEC) cream may provide new antibacterial preparations for human infections. Our results demonstrate that TCUCAP1 displays several features that make it an ideal candidate for the control of C. acnes infections.

Evaluation on the use of Nanopore sequencing for direct characterization of coronaviruses from respiratory specimens, and a study on emerging missense mutations in partial RdRP gene of SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) pandemic has been a catastrophic burden to global healthcare systems. The fast spread of the etiologic agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights the need to identify unknown coronaviruses rapidly for prompt clinical and public health decision making. Moreover, owing to the high mutation rate of RNA viruses, periodic surveillance on emerging variants of key virus components is essential for evaluating the efficacy of antiviral drugs, diagnostic assays and vaccines. These 2 knowledge gaps formed the basis of this study. In the first place, we evaluated the feasibility of characterizing coronaviruses directly from respiratory specimens. We amplified partial RdRP gene, a stable genetic marker of coronaviruses, from a collection of 57 clinical specimens positive for SARS-CoV-2 or other human coronaviruses, and sequenced the amplicons with Nanopore Flongle and MinION, the fastest and the most scalable massively-parallel sequencing platforms to-date. Partial RdRP sequences were successfully amplified and sequenced from 82.46% (47/57) of specimens, ranging from 75 to 100% by virus type, with consensus accuracy of 100% compared with Sanger sequences available (n = 40). In the second part, we further compared 19 SARS-CoV-2 RdRP sequences collected from the first to third waves of COVID-19 outbreak in Hong Kong with 22,173 genomes from GISAID EpiCoV™ database. No single nucleotide variants (SNVs) were found in our sequences, and 125 SNVs were observed from global data, with 56.8% being low-frequency (n = 1-47) missense mutations affecting the rear part of RNA polymerase. Among the 9 SNVs found on 4 conserved domains, the frequency of 15438G > T was highest (n = 34) and was predominantly found in Europe. Our data provided a glimpse into the sequence diversity of a primary antiviral drug and diagnostic target. Further studies are warranted to investigate the significance of these mutations.

Comparative evaluation of a laboratory-developed real-time PCR assay and RealStar® Adenovirus PCR Kit for quantitative detection of human adenovirus.

BACKGROUND: Human adenoviruses are common causes of community-acquired respiratory tract and enteric infections. Severe disseminated infections with high mortality rates may be seen in immunocompromised individuals. An accurate and cost-effective quantitative assay is essential not only for laboratory diagnosis of adenoviral infections, but also for monitoring of response to antiviral treatment. The diagnostic performance of an in-house quantitative polymerase chain reaction assay was compared to a commercial system. METHODS: The analytical sensitivity, specificity, linearity, precision and accuracy of an in-house adenovirus quantitative polymerase chain reaction assay were evaluated against the RealStar® Adenovirus PCR Kit (Altona Diagnostics GmbH, Hamburg, Germany), using 122 clinical specimens and 18 proficiency testing samples. RESULTS: Linear regression analysis of the quantitative results by the in-house assay showed the dynamic range from 2.60 to 9 log10 (plasma) and 2.94 to 9 log10 (viral transport medium) copies/mL, with the coefficient of determination (R2) of 0.996 and 0.998, respectively. A dilution series demonstrated the limits of detection and lower limits of quantification for plasma were 2.06 log10 and 2.60 log10 copies/mL and those for viral transport medium were 2.31 log10 and 2.94 log10 copies/mL respectively. The precision of the in-house assay was highly reproducible among runs with coefficients of variance ranging from 0.07 to 3.21% for plasma and 0.17% to 2.11% for viral transport medium. A comparison of 52 matched samples showed an excellent correlation between the quantitative viral loads measured by the in-house assay and the RealStar® Adenovirus PCR Kit (R2 = 0.984), with an average bias of - 0.16 log10 copies/mL. CONCLUSIONS: The in-house adenovirus assay is a sensitive and reliable assay with lower cost for the detection and quantification of adenoviral DNA when compared to the RealStar® Adenovirus PCR Kit.

Synthesis and antibacterial studies of teixobactin analogues with non-isostere substitution of enduracididine.

Teixobactin is a structurally and mechanistically novel antimicrobial peptide with potent activities against Gram-positive pathogens. It contains l-allo-enduracididine (End) residue which is not readily accessible. In this report, we have used convergent Ser Ligation as the key step to prepare a series of teixobactin analogues with End being substituted with its non-isostere moieties. Among these analogues, compounds T16, T27 and T29 exhibited the best antimicrobial activities against different Gram-positive bacteria with MICs ranging from 0.25 to 1.0 µM. Structure-activity relationship is also established for further development of more promising teixobactin analogues.

The Polarized Effect of Intracellular Calcium on the Renal Epithelial Sodium Channel Occurs as a Result of Subcellular Calcium Signaling Domains Maintained by Mitochondria.

The renal epithelial sodium channel (ENaC) provides regulated sodium transport in the distal nephron. The effects of intracellular calcium ([Ca(2+)]i) on this channel are only beginning to be elucidated. It appears from previous studies that the [Ca(2+)]i increases downstream of ATP administration may have a polarized effect on ENaC, where apical application of ATP and the subsequent [Ca(2+)]i increase have an inhibitory effect on the channel, whereas basolateral ATP and [Ca(2+)]i have a stimulatory effect. We asked whether this polarized effect of ATP is, in fact, reflective of a polarized effect of increased [Ca(2+)]i on ENaC and what underlying mechanism is responsible. We began by performing patch clamp experiments in which ENaC activity was measured during apical or basolateral application of ionomycin to increase [Ca(2+)]i near the apical or basolateral membrane, respectively. We found that ENaC does indeed respond to increased [Ca(2+)]i in a polarized fashion, with apical increases being inhibitory and basolateral increases stimulating channel activity. In other epithelial cell types, mitochondria sequester [Ca(2+)]i, creating [Ca(2+)]i signaling microdomains within the cell that are dependent on mitochondrial localization. We found that mitochondria localize in bands just beneath the apical and basolateral membranes in two different cortical collecting duct principal cell lines and in cortical collecting duct principal cells in mouse kidney tissue. We found that inhibiting mitochondrial [Ca(2+)]i uptake destroyed the polarized response of ENaC to [Ca(2+)]i. Overall, our data suggest that ENaC is regulated by [Ca(2+)]i in a polarized fashion and that this polarization is maintained by mitochondrial [Ca(2+)]i sequestration.

Clinical Evaluation of the New High-Throughput Luminex NxTAG Respiratory Pathogen Panel Assay for Multiplex Respiratory Pathogen Detection.

A broad range of viral and bacterial pathogens can cause acute respiratory tract infection. For rapid detection of a broad respiratory pathogen spectrum, multiplex real-time PCR is ideal. This study evaluated the performance of the new Luminex NxTAG Respiratory Pathogen Panel (NxTAG-RPP) in comparison with the BioFire FilmArray Respiratory Panel (FA-RP) or singleplex real-time PCR as reference. A total of 284 clinical respiratory specimens and 3 influenza A/H7N9 viral culture samples were tested. All clinical specimens were processed and analyzed in parallel using NxTAG-RPP and the reference standard method. The H7N9 viral culture samples were tested using NxTAG-RPP only. Overall, the NxTAG-RPP demonstrated ≥93% sensitivity and specificity for all respiratory targets except human coronavirus OC43 (HCoV-OC43) and HCoV-HKU1. The H7N9 virus was detected by the influenza A virus matrix gene target, while other influenza A virus subtyping gene targets in the panel remained negative. Complete concordance between NxTAG-RPP and FA-RP was observed in 98.8% (318/322) of positive results (kappa = 0.92). Substantial agreement was found for most respiratory targets, but significant differences were observed in human metapneumovirus (P = 0.001) and parainfluenza virus type 3 (P = 0.031). NxTAG-RPP has a higher sample throughput than FA-RP (96 samples versus 1 sample per run) while the turnaround times for NxTAG-RPP and FA-RP were 5 h (up to 96 samples) and 1 h (for one sample), respectively. Overall, NxTAG-RPP demonstrated good diagnostic performance for most respiratory pathogens. The high sample throughput with reasonable turnaround time of this new assay makes it a suitable multiplex platform for routine screening of respiratory specimens in hospital-based laboratories.

Development and Evaluation of Novel Real-Time Reverse Transcription-PCR Assays with Locked Nucleic Acid Probes Targeting Leader Sequences of Human-Pathogenic Coronaviruses.

Based on findings in small RNA-sequencing (Seq) data analysis, we developed highly sensitive and specific real-time reverse transcription (RT)-PCR assays with locked nucleic acid probes targeting the abundantly expressed leader sequences of Middle East respiratory syndrome coronavirus (MERS-CoV) and other human coronaviruses. Analytical and clinical evaluations showed their noninferiority to a commercial multiplex PCR test for the detection of these coronaviruses.

Bridging the sanitation gap between disaster relief and development.

By interpreting disasters as opportunities to initiate the fulfilment of development needs, realise the vulnerability of the affected community and environment, and extend the legacy of relief funds and effort, this paper builds upon the concept linking relief, rehabilitation and development (LRRD) in the sanitation sector. It aims to use a composite of case studies to devise a framework for a semi-hypothetical scenario to identify critical components and generic processes for a LRRD action plan. The scenario is based on a latrine wetland sanitation system in a Muslim community. Several sub-frameworks are developed: (i) latrine design; (ii) assessment of human waste treatment; (iii) connective sanitation promotion strategy; and (iv) ecological systems and environmental services for sanitation and development. This scenario illustrates the complex issues involved in LRRD in sanitation work and provides technical notes and references for a legacy plan for disaster relief and development.

Basolateral P2X4channels stimulate ENaC activity in Xenopus cortical collecting duct A6 cells.

The polarized nature of epithelial cells allows for different responses to luminal or serosal stimuli. In kidney tubules, ATP is produced luminally in response to changes in luminal flow. Luminal increases in ATP have been previously shown to inhibit the renal epithelial Na⁺ channel (ENaC). On the other hand, ATP is increased basolaterally in renal epithelia in response to aldosterone. We tested the hypothesis that basolateral ATP can stimulate ENaC function through activation of the P2X4receptor/channel. Using single channel cell-attached patch-clamp techniques, we demonstrated the existence of a basolaterally expressed channel stimulated by the P2X4agonist 2-methylthio-ATP (meSATP) in Xenopus A6 cells, a renal collecting duct principal cell line. This channel had a similar reversal potential and conductance to that of P2X4channels. Cell surface biotinylation of the basolateral side of these cells confirmed the basolateral presence of the P2X4 receptor. Basolateral addition of meSATP enhanced the activity of ENaC in single channel patch-clamp experiments, an effect that was absent in cells transfected with a dominant negative P2X4receptor construct, indicating that activation of P2X4channels stimulates ENaC activity in these cells. The effect of meSATP on ENaC activity was reduced after chelation of basolateral Ca²âº with EGTA or inhibition of phosphatidylinositol 3-kinase with LY-294002. Overall, our results show that ENaC is stimulated by P2X4receptor activation and that the stimulation is dependent on increases in intracellular Ca²âº and phosphatidylinositol 3-kinase activation.

Intratumoral Microbiota: Unraveling their Oncogenic Impact on Cancer Progression With Focus on Breast Cancer Therapeutic Outcomes.

The gut microbiota has been implicated in many cancers through the secretion of blood-traveling metabolites or activation of oncogenic signaling. Currently, specific microbial signatures have been detected in the human breast, which are different from other microbial-rich compartments, such as the intestine and skin. Changes in the breast microbiome profile have been shown to positively or negatively correlate with breast cancer development, progression, and therapeutic outcomes. However, studies regarding the role and underlying mechanism of intratumoral microbiota in breast cancer have remained concealed. This review aimed to provide an overview of the role of the intratumoral microbiome in tumorigenesis and tumor progression, and how these intratumoral microbiota affect breast cancer. We also discuss the potential of using the intratumoral microbiome as a biomarker or treatment alternative in breast cancers.

The Use of Schisandrin B to Combat Triple-Negative Breast Cancers by Inhibiting NLRP3-Induced Interleukin-1ß Production.

Triple-negative breast cancer (TNBC) is the most aggressive and fatal breast cancer subtype. Nowadays, chemotherapy remains the standard treatment of TNBC, and immunotherapy has emerged as an important alternative. However, the high rate of TNBC recurrence suggests that new treatment is desperately needed. Schisandrin B (Sch B) has recently revealed its anti-tumor effects in cancers such as cholangiocarcinoma, hepatoma, glioma, and multi-drug-resistant breast cancer. However, there is still a need to investigate using Sch B in TNBC treatment. Interleukin (IL)-1ß, an inflammatory cytokine that can be expressed and produced by the cancer cell itself, has been suggested to promote BC proliferation and progression. In the current study, we present evidence that Sch B can significantly suppress the growth, migration, and invasion of TNBC cell lines and patient-derived TNBC cells. Through inhibition of inflammasome activation, Sch B inhibits interleukin (IL)-1ß production of TNBC cells, hindering its progression. This was confirmed using an NLRP3 inhibitor, OLT1177, which revealed a similar beneficial effect in combating TNBC progression. Sch B treatment also inhibits IL-1ß-induced EMT expression of TNBC cells, which may contribute to the anti-tumor response.

Mechanism of CDK4/6 Inhibitor Resistance in Hormone Receptor-positive Breast Cancer and Alternative Treatment Strategies.

Breast cancer (BC) is a common malignancy in women, with hormone receptor (HR)-positive subtype responsible for approximately 70% of cases. Currently, patients with metastatic HR-positive BC rely on endocrine therapy and cyclin-dependent kinase (CDK)-4/6 inhibitors for treatment. Currently, approved CDK4/6 inhibitors include palbociclib, ribociclib, and abemaciclib. However, clinical evidence of CDK-4/6 inhibitor resistance is emerging, suggesting that the gap in the knowledge of its resistance mechanism requires further investigation. This review discusses the mechanisms of CDK4/6 inhibitor resistance in BC, including both intrinsic and extrinsic mechanisms. We also discuss possible alternative strategies to overcome CDK4/6 inhibitor resistance in future clinical applications.

Metaplastic Carcinoma of the Axillary Breast With Heterologous Mesenchymal (Chondroid) Differentiation: A Difficult Case and Literature Review.

Metaplastic breast carcinoma is an invasive carcinoma with a high differentiation rate of the neoplastic epithelium toward mesenchymal-like epithelium. It comprises of only less than 1% of all breast cancers. Although 80% to 90% of metaplastic breast carcinomas are triple-negative cancers, they usually have worse outcomes than other triple-negative breast cancers (TNBCs). Metaplastic carcinoma is also often refractory to cytotoxic chemotherapy. Here, we reported a case of a 61-year-old female patient, presenting with a solitary and pedunculated mass in the right axillary tail breast tissue, whose biopsy revealed metaplastic breast carcinoma with chondroid differentiation. She had failed neoadjuvant chemotherapy and immunotherapy. Although she received debulking surgery, the tumor regrew even faster before surgery. Despite receiving palliative chemotherapy, the patient died 11 weeks after surgery. This case draws attention to physicians that early recognition and surgery may be more beneficial than chemotherapy in combating metaplastic breast carcinoma.

Prevention of the Pro-Aggressive Effects of Ethanol-Intoxicated Mice by Schisandrin B.

Excessive alcohol consumption can lead to serious health complications, with liver and neurological complications being the most important. In Western nations, alcoholic liver disease accounts for 50% of mortality from end-stage liver disease and is the second most common cause of liver transplants. In addition to direct damage, hepatic encephalopathy may also arise from alcohol consumption. However, effective treatment for liver disease, as well as neurological injury, is still lacking today; therefore, finding an efficacious alternative is urgently needed. In the current study, the preventive and therapeutic effects of Schisandrin B (Sch B) against ethanol-induced liver and brain injuries were investigated. By using two treatment models, our findings indicated that Sch B can effectively prevent and ameliorate alcoholic liver diseases, such as resolving liver injuries, lipid deposition, inflammasome activation, and fibrosis. Moreover, Sch B reverses brain damage and improves the neurological function of ethanol-treated mice. Therefore, Sch B may serve as a potential treatment option for liver diseases, as well as subsequential brain injuries. Furthermore, Sch B may be useful in preventive drug therapy against alcohol-related diseases.

Salmonella typhimurium exacerbates injuries but resolves fibrosis in liver and spleen during Schistosoma mansoni infection.

BACKGROUND: In most developing or undeveloped countries, patients are often co-infected with multiple pathogens rather than a single pathogen. While different pathogens have their impact on morbidity and mortality, co-infection of more than one pathogen usually made the disease outcome different. Many studies reported the co-infection of Schistosoma with Salmonella in pandemic areas. However, the link or the underlying mechanism in the pathogenesis caused by Schistosoma-Salmonella co-infection is still unknown. METHODS: In this study, Salmonella typhimurium (S. typhimurium) was challenged to Schistosoma mansoni (S. mansoni)-infected mice. Further experiments such as bacterial culture, histopathological examination, western blotting, and flow cytometry were performed to evaluate the outcomes of the infection. Cytokine responses of the mice were also determined by ELISA and real-time quantitative PCR. RESULTS: Our results demonstrated that co-infected mice resulted in higher bacterial excretion in the acute phase but higher bacterial colonization in the chronic phase. Lesser egg burden was also observed during chronic schistosomiasis. Infection with S. typhimurium during schistosomiasis induces activation of the inflammasome and apoptosis, thereby leading to more drastic tissue damage. Interestingly, co-infected mice showed a lower fibrotic response in the liver and spleen. Further, co-infection alters the immunological functioning of the mice, possibly the reason for the observed pathological outcomes. CONCLUSION: Collectively, our findings here demonstrated that S. mansoni-infected mice challenged with S. typhimurium altered their immunological responses, thereby leading to different pathological outcomes.

Isolation and characterization of bacteriophages with activities against multi-drug-resistant Acinetobacter nosocomialis causing bloodstream infection in vivo.

BACKGROUND: Acinetobacter nosocomialis (A. nosocomialis) is a glucose non-fermentative, gram-negative bacillus that belongs to the Acinetobacter calcoaceticus-baumannii complex. In recent years, studies have found an increased clinical prevalence of A. nosocomialis. However, given the increasing trend of antibiotic resistance, developing new antibacterial agents is vital. Currently, research regarding bacteriophage therapy against A. nosocomialis is only limited. METHODS: Two A. nosocomialis bacteriophages, TCUAN1 and TCUAN2, were isolated from sewage. Experiments such as transmission electron microscopy (TEM), host-range analysis, and sequencing were performed to determine their biological and genomic characteristics. TCUAN2 were further subjected to in vivo experiments and their derived-endolysin were cloned and tested against their bacteria host. RESULTS: Transmission electron microscopy revealed that TCUAN1 and TCUAN2 belong to Myoviridae and Podoviridae, respectively. Both phages show a broad host spectrum and rapid adsorption efficiency. Further biological analysis showed that TCUAN2 possesses a shorter latent period and larger burst size compared to TCUAN1. Because TCUAN2 showed a better antibacterial activity, it was injected into A. nosocomialis-infected mice which resulted in a significant decrease in bacterial load levels in the blood and increased the mice's survival. Finally, genomic analysis revealed that the complete nucleotide sequence of TCUAN1 is 49, 691 bps (containing 75 open reading frames) with a G + C content of 39.3%; whereas the complete nucleotide sequence of TCUAN2 is 41, 815 bps (containing 68 open reading frames) with a G + C content of 39.1%. The endolysin gene cloned and purified from TCUAN2 also showed antibacterial activity when used with a chelator EDTA.

Resolution of systemic complications in Schistosoma mansoni-infected mice by concomitant treatment with praziquantel and Schisandrin B.

Schistosomiasis is a tropical parasitic disease, in which the major clinical manifestation includes hepatosplenomegaly, portal hypertension, and organs fibrosis. Clinically, treatment of schistosomiasis involves the use of praziquantel (PZQ) and supportive care, which does not improve the patient's outcome as liver injuries persist. Here we show the beneficial effects of using PZQ in combination with Schisandrin B (Sch B). Concomitant treatment with PZQ and Sch B resulted in a significant improvement of hepatosplenomegaly and fibrosis, compared with single-agent treatment. We also demonstrated that PZQ-Sch B treatment ameliorates injuries in the lungs and intestine better than the sole use of PZQ or Sch B. In addition, PZQ-Sch B treatment improves the survival of S. mansoni-infected mice, and the treatment combination yields better therapeutic outcomes, as indicated by a partial improvement in neurological function. These results were accompanied by a reduction in neurological injuries. Collectively, we suggest that PZQ-Sch B concomitant therapy may be useful to alleviate schistosomiasis-associated liver injuries and prevent systemic complications.

Use of wogonin as a cooperative drug with praziquantel to better combat schistosomiasis.

BACKGROUND: Schistosomiasis is one of the most devastating tropical diseases in the world. Currently, praziquantel (PZQ) represents the best pharmacological option for the treatment of schistosomiasis as it effectively kills the worm. However, the inability to reverse established liver damages often makes treatment futile. In the current study, we investigate whether combining the use of wogonin, a compound that was found to be liver-protective, with PZQ can attribute to the greatest beneficial effect in Schistosoma mansoni-infected mice. METHODS: To determine the protective effect of PZQ-wogonin treatment on S. manosni-infected mice, histopathological analysis was done to evaluate the granuloma size and fibrotic areas in the liver. Western blotting was performed to analyze several injuries-related markers including fibrotic markers, inflammasomes, and apoptotic markers. Scanning electron microscopy was done to evaluate the effect of wogonin on the worms, and the worm and egg burden was calculated. RESULTS: Our results showed that PZQ-wogonin treatment significantly improved liver histopathology of S. mansoni-infected mice. Further analysis showed that PZQ-wogonin combinations are more effective in reducing fibrosis, inflammation, and apoptosis in the liver than that of individual drug use. Furthermore, our results revealed that wogonin is anthelmintic; and it works better with PZQ in reducing hepatic egg burden, further lessen the disease progression. CONCLUSION: In general, this combinatorial strategy may represent a new and effective approach to schistosomiasis treatment.