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This article discusses a case study of a 32-year-old female who presented with cobblestone-like plaques on her lower extremity, resembling elephantiasis. The patient had previously undergone dermatoplasty for suspected elephantiasis, but the current lesions were found to be eccrine syringofibroadenoma (ESFA), a rare cutaneous adnexal neoplasm. The histopathological examination revealed anastomosing epithelial strands extending from the epidermis into the dermis, with ductal differentiation. The authors suggest that the ESFA in this case may be reactive to the scars, chronic inflammation, and lymphedema. The recommended treatment is complete excision, but unfortunately, the patient was lost to follow-up. The article also discusses the potential risk factors for skin tumors, such as cutaneous trauma and the role of cicatrization and chronic inflammation in tumorigenesis. [Extracted from the article]

Psoriasis is a chronic inflammatory skin disorder with a chronic relapsing course. Biologics have revolutionized the treatment of adult psoriasis with higher efficacy and favorable safety profile. Recently, more studies have focused on the use of biologics in pediatric psoriasis, and several biologics have been approved for use therein. This review is divided into two sections: the first part focuses on real‐world studies on the use of biologics in pediatric psoriasis and the second part summarizes the findings of other clinical trials related to biologics in pediatric psoriasis. Case reports have been excluded from this review. Several biologics were used for treating pediatric psoriasis and the efficacy is encouraging. According to the studies included in this review, anti‐IL‐12/23 and anti‐IL‐17A for treating pediatric psoriasis might have a better efficacy than anti‐TNF‐α, but more data are needed. [ABSTRACT FROM AUTHOR]

Summary: Arabidopsis RESISTANCE TO POWDERY MILDEW 8.2 (RPW8.2) is specifically induced by the powdery mildew (PM) fungus (Golovinomyces cichoracearum) in the infected epidermal cells to activate immunity. However, the mechanism of RPW8.2‐induction is not well understood.Here, we identify a G. cichoracearum effector that interacts with RPW8.2, named Gc‐RPW8.2 interacting protein 1 (GcR8IP1), by a yeast two‐hybrid screen of an Arabidopsis cDNA library.GcR8IP1 is physically associated with RPW8.2 with its REALLY INTERESTING NEW GENE finger domain that is essential and sufficient for the association. GcR8IP1 was secreted and translocated into the nucleus of host cell infected with PM. Association of GcR8IP1 with RPW8.2 led to an increase in RPW8.2 in the nucleus. In turn, the nucleus‐localized RPW8.2 promoted the activity of the RPW8.2 promoter, resulting in transcriptional self‐amplification of RPW8.2 to boost immunity at infection sites. Additionally, ectopic expression or host‐induced gene silencing of GcR8IP1 supported its role as a virulence factor in PM.Altogether, our results reveal a mechanism of RPW8.2‐dependent defense strengthening via altered partitioning of RPW8.2 and transcriptional self‐amplification triggered by a PM fungal effector, which exemplifies an atypical form of effector‐triggered immunity. [ABSTRACT FROM AUTHOR]

Summary: Rice production is threatened by multiple pathogens. Breeding cultivars with broad‐spectrum disease resistance is necessary to maintain and improve crop production. Previously we found that overexpression of miR160a enhanced rice blast disease resistance. However, it is unclear whether miR160a also regulates resistance against other pathogens, and what the downstream signaling pathways are.Here, we demonstrate that miR160a positively regulates broad‐spectrum resistance against the causative agents of blast, leaf blight and sheath blight in rice. Mutations of miR160a‐targeted Auxin Response Factors result in different alteration of resistance conferred by miR160a. miR160a enhances disease resistance partially by suppressing ARF8, as mutation of ARF8 in MIM160 background partially restores the compromised resistance resulting from MIM160.ARF8 protein binds directly to the promoter and suppresses the expression of WRKY45, which acts as a positive regulator of rice immunity. Mutation of WRKY45 compromises the enhanced blast resistance and bacterial leaf blight resistance conferred by arf8 mutant.Overall, our results reveal that a microRNA coordinates rice broad‐spectrum disease resistance by suppressing multiple target genes that play different roles in disease resistance, and uncover a new regulatory pathway mediated by the miR160a‐ARF8 module. These findings provide new resources to potentially improve disease resistance for breeding in rice. [ABSTRACT FROM AUTHOR]

Summary: Rice false smut caused by Ustilaginoidea virens is becoming one of the most recalcitrant rice diseases worldwide. However, the molecular mechanisms underlying rice immunity against U. virens remain unknown.Using genetic, biochemical and disease resistance assays, we demonstrated that the xb24 knockout lines generated in non‐Xa21 rice background exhibit an enhanced susceptibility to the fungal pathogens U. virens and Magnaporthe oryzae. Consistently, flg22‐ and chitin‐induced oxidative burst and expression of pathogenesis‐related genes in the xb24 knockout lines were greatly attenuated.As a central mediator of energy signaling, SnRK1A interacts with and phosphorylates XB24 at Thr83 residue to promote ATPase activity. SnRK1A is activated by pathogen‐associated molecular patterns and positively regulates plant immune responses and disease resistance. Furthermore, the virulence effector SCRE1 in U. virens targets host ATPase XB24. The interaction inhibits ATPase activity of XB24 by blocking ATP binding to XB24. Meanwhile, SCRE1 outcompetes SnRK1A for XB24 binding, and thereby suppresses SnRK1A‐mediated phosphorylation and ATPase activity of XB24.Our results indicate that the conserved SnRK1A‐XB24 module in multiple crop plants positively contributes to plant immunity and uncover an unidentified molecular strategy to promote infection in U. virens and a novel host target in fungal pathogenesis. [ABSTRACT FROM AUTHOR]

Summary: MicroRNAs (miRNAs) play vital roles in plant development and defence responses against various stresses. Here, we show that blocking miR1871 improves rice resistance against Magnaporthe oryzae and enhances grain yield simultaneously. The transgenic lines overexpressing miR1871 (OX1871) exhibit compromised resistance, suppressed defence responses and reduced panicle number resulting in slightly decreased yield. In contrast, the transgenic lines blocking miR1871 (MIM1871) show improved resistance, enhanced defence responses and significantly increased panicle number leading to enhanced yield per plant. The RNA‐seq assay and defence response assays reveal that blocking miR1871 resulted in the enhancement of PAMP‐triggered immunity (PTI). Intriguingly, miR1871 suppresses the expression of LOC_Os06g22850, which encodes a microfibrillar‐associated protein (MFAP1) locating nearby the cell wall and positively regulating PTI responses. The mutants of MFAP1 resemble the phenotype of OX1871. Conversely, the transgenic lines overexpressing MFAP1 (OXMFAP1) or overexpressing both MFAP1 and miR1871 (OXMFAP1/OX1871) resemble the resistance of MIM1871. The time‐course experiment data reveal that the expression of miR1871 and MFAP1 in rice leaves, panicles and basal internode is dynamic during the whole growth period to manipulate the resistance and yield traits. Our results suggest that miR1871 regulates rice yield and immunity via MFAP1, and the miR8171‐MFAP1 module could be used in rice breeding to improve both immunity and yield. [ABSTRACT FROM AUTHOR]

SUMMARY Many rice microRNAs have been identified as fine‐tuning factors in the regulation of agronomic traits and immunity. Among them, Osa‐miR535 targets SQUAMOSA promoter binding protein‐like 14 (OsSPL14) to positively regulate tillers but negatively regulate yield and immunity. Here, we uncovered that Osa‐miR535 targets another SPL gene, OsSPL4, to suppress rice immunity against Magnaporthe oryzae. Overexpression of Osa‐miR535 significantly decreased the accumulation of the fusion protein SPL4TBS‐YFP that contains the target site of Osa‐miR535 in OsSPL4. Consistently, Osa‐miR535 mediated the cleavage of OsSPL4 mRNA between the 10th and 11th base pair of the predicted binding site at the 3′ untranslated region. Transgenic rice lines overexpressing OsSPL4 (OXSPL4) displayed enhanced blast disease resistance accompanied by enhanced immune responses, including increased expression of defense‐relative genes and up‐accumulated H2O2. By contrast, the knockout mutant osspl4 exhibited susceptibility. Moreover, OsSPL4 binds to the promoter of GH3.2, an indole‐3‐acetic acid‐amido synthetase, and promotes its expression. Together, these data indicate that Os‐miR535 targets OsSPL4 and OsSPL4‐GH3.2, which may parallel the OsSPL14‐WRKY45 module in rice blast disease resistance. Significance Statement: Previously, Osa‐miR535 was identified to target SPL14 to regulate rice immunity. Here, we identified that Osa‐miR535 targets another SPL family gene, OsSPL4. OsSPL4 binds the promoter of GH3.2 to positively regulate rice immunity, which functionally parallels with OsSPL14‐WRKY45 module downstream of Osa‐miR535. [ABSTRACT FROM AUTHOR]

Study on the regulation of broad‐spectrum resistance is an active area in plant biology. RESISTANCE TO POWDERY MILDEW 8.1 (RPW8.1) is one of a few broad‐spectrum resistance genes triggering the hypersensitive response (HR) to restrict multiple pathogenic infections. To address the question how RPW8.1 signaling is regulated, we performed a genetic screen and tried to identify mutations enhancing RPW8.1‐mediated HR. Here, we provided evidence to connect an annexin protein with RPW8.1‐mediated resistance in Arabidopsis against powdery mildew. We isolated and characterized Arabidopsis b7‐6 mutant. A point mutation in b7‐6 at the At5g12380 locus resulted in an amino acid substitution in ANNEXIN 8 (AtANN8). Loss‐of‐function or RNA‐silencing of AtANN8 led to enhanced expression of RPW8.1, RPW8.1‐dependent necrotic lesions in leaves, and defense against powdery mildew. Conversely, over‐expression of AtANN8 compromised RPW8.1‐mediated disease resistance and cell death. Interestingly, the mutation in AtANN8 enhanced RPW8.1‐triggered H2O2. In addition, mutation in AtANN8 led to hypersensitivity to salt stress. Together, our data indicate that AtANN8 is involved in multiple stress signaling pathways and negatively regulates RPW8.1‐mediated resistance against powdery mildew and cell death, thus linking ANNEXIN's function with plant immunity. [ABSTRACT FROM AUTHOR]

Summary: The Arabidopsis RESISTANCE TO POWDERY MILDEW 8.1 (RPW8.1) activates confined cell death and defense against different pathogens. However, the underlying regulatory mechanisms still remain elusive.Here, we show that RPW8.1 activates ethylene signaling that, in turn, negatively regulates RPW8.1 expression. RPW8.1 binds and stabilizes 1‐aminocyclopropane‐1‐carboxylate oxidase 4 (ACO4), which may in part explain increased ethylene production and signaling in RPW8.1‐expressing plants. In return, ACO4 and other key components of ethylene signaling negatively regulate RPW8.1‐mediated cell death and disease resistance via suppressing RPW8.1 expression.Loss of function in ACO4, EIN2, EIN3 EIL1, ERF6, ERF016 or ORA59 increases RPW8.1‐mediated cell death and defense response. By contrast, overexpression of EIN3 abolishes or significantly compromises RPW8.1‐mediated cell death and disease resistance. Furthermore, ERF6, ERF016 and ORA59 appear to act as trans‐repressors of RPW8.1, with OAR59 being able to directly bind to the RPW8.1 promoter.Taken together, our results have revealed a feedback regulatory circuit connecting RPW8.1 and the ethylene‐signaling pathway, in which RPW8.1 enhances ethylene signaling, and the latter, in return, negatively regulates RPW8.1‐mediated cell death and defense response via suppressing RPW8.1 expression to attenuate its defense activity. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are known to fine‐tune growth, development, and stress‐induced responses. Osa‐miR1873 is a rice‐specific miRNA targeting LOC_Os05g01790. Here, we show that Osa‐miR1873 fine‐tunes rice immunity against Magnaporthe oryzae and yield traits via LOC_Os05g01790. Osa‐miR1873 was significantly upregulated in a susceptible accession but downregulated in a resistance accession at 24 h post‐inoculation (hpi) of M. oryzae. Overexpressing Osa‐miR1873 enhanced susceptibility to M. oryzae and compromised induction of defense responses. In contrast, blocking Osa‐miR1873 through target mimicry compromised susceptibility to M. oryzae and enhanced induction of defense responses. Altered expression of Osa‐miR1873 also resulted in some defects in yield traits, including grain numbers and seed setting rate. Moreover, overexpression of the target gene LOC_Os05g01790 increased rice blast disease resistance but severely penalized growth and yield. Taken together, we demonstrate that Osa‐miR1873 fine‐tunes the rice immunity‐growth trade‐off via LOC_Os05g01790, and blocking Osa‐miR1873 could improve blast disease resistance without significant yield penalty. Thus, the Osa‐miR1873‐LOC_Os05g01790 regulatory module is valuable in balancing yield traits and blast resistance. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) play important roles in rice response to Magnaporthe oryzae, the causative agent of rice blast disease. Studying the roles of rice miRNAs is of great significance for the disease control. Osa‐miR167d belongs to a conserved miRNA family targeting auxin responsive factor (ARF) genes that act in developmental and stress‐induced responses. Here, we show that Osa‐miR167d plays a negative role in rice immunity against M. oryzae by suppressing its target gene. The expression of Osa‐miR167d was significantly suppressed in a resistant accession at and after 24 h post inoculation (hpi), however, its expression was significantly increased at 24 hpi in the susceptible accession upon M. oryzae infection. Transgenic rice lines over‐expressing Osa‐miR167d were highly susceptible to multiple blast fungal strains. By contrast, transgenic lines expressing a target mimicry to block Osa‐miR167d enhanced resistance to rice blast disease. In addition, knocking out the target gene ARF12 led to hyper‐susceptibility to multiple blast fungal strains. Taken together, our results indicate that Osa‐miR167d negatively regulate rice immunity to facilitate the infection of M. oryzae by downregulating ARF12. Thus, Osa‐miR167d‐ARF12 regulatory module could be valuable in improvement of blast‐disease resistance. [ABSTRACT FROM AUTHOR]

Summary: miRNAs contribute to plant resistance against pathogens. Previously, we found that the function of miR398b in immunity in rice differs from that in Arabidopsis. However, the underlying mechanisms are unclear.In this study, we characterized the mutants of miR398b target genes and demonstrated that multiple superoxide dismutase genes contribute to miR398b‐regulated rice immunity against the blast fungus Magnaporthe oryzae.Out of the four target genes of miR398b, mutations in Cu/Zn‐Superoxidase Dismutase1 (CSD1), CSD2 and Os11g09780 (Superoxide DismutaseX,SODX) led to enhanced resistance to M. oryzae and increased hydrogen peroxide (H2O2) accumulation. By contrast, mutations in Copper Chaperone for Superoxide Dismutase (CCSD) resulted in enhanced susceptibility. Biochemical studies revealed that csd1, csd2 and sodx displayed altered expression of CSDs and other superoxide dismutase (SOD) family members, leading to increased total SOD enzyme activity that positively contributed to higher H2O2 production. By contrast, the ccsd mutant showed CSD protein deletion, resulting in decreased CSD and total SOD enzyme activity.Our results demonstrate the roles of different SODs in miR398b‐regulated resistance to rice blast disease, and uncover an integrative regulatory network in which miR398b boosts total SOD activity to upregulate H2O2 concentration and thereby improve disease resistance. [ABSTRACT FROM AUTHOR]

Summary: The extrahaustorial membrane (EHM) is a host‐derived interfacial membrane encasing the haustorium of powdery mildew fungi. Arabidopsis thaliana RESISTANCE TO POWDERY MILDEW 8.2 (RPW8.2) is specifically targeted to the EHM via two EHM‐targeting signals. Here, we demonstrate that proper coordination between the trafficking forces engaged via the EHM‐targeting signals and the nuclear localization signals (NLSs), as well as the nuclear export signals (NESs), in RPW8.2 is critical for the activation of cell death and defense. We show that in the absence of pathogens, RPW8.2 is partitioned between the cytoplasm and the nucleus, and turned over via both the 26S proteasome‐ and the vacuole‐dependent pathways. Enhanced cytoplasmic localization of RPW8.2 by tagging it with a NES led to lethal cell death. By contrast, enhanced nuclear localization of RPW8.2 by adding an NLS to it resulted in resistance to powdery mildew. Whereas expression of the NES‐containing C‐terminal domain of RPW8.2 in the cytoplasm is sufficient to trigger cell death, no such cell death‐inducing activity is found with RPW8.2 variants that contain the two EHM‐targeting signals along with the NES‐containing C‐terminal domain. In addition, we present evidence for the involvement of a leaf senescence pathway in RPW8.2‐mediated cell death and defense. Taken together, our data suggest that RPW8.2 is subject to adjustment by distinct and perhaps coordinated mechanisms for its localization and function via interaction with the multiple intramolecular trafficking signals, which should provide further insights into RPW8.2‐activated, EHM‐focused resistance against powdery mildew. Significance Statement: The Arabidopsis thaliana RPW8.2 is specifically targeted to the host‐fungal interface (i.e., the extrahaustorial membrane; EHM) and confers broad‐spectrum resistance against powdery mildew in a dosage‐dependent manner. Our data from this study suggest that multiple trafficking mechanisms coordinately adjust RPW8.2‐mediated cell death and defense via the EHM‐targeting signals and the nuclear localization/export signals present in RPW8.2. [ABSTRACT FROM AUTHOR]

Exosomes are membrane vesicles of endocytic origin that can mediate communication between cells and the transport of cellular components such as microRNAs, mRNAs, proteins and DNA. Recently, exosomes have been under investigation for their significant roles in both healthy physiology and disease states. Herein, we review the role of exosomes in chronic inflammatory skin diseases and skin tumors, especially focusing on systemic lupus erythematosus, psoriasis, atopic dermatitis, bullous pemphigoid and melanoma. Moreover, we emphasize the involvement of changes in exosome cargo in the regulation of these diseases. [ABSTRACT FROM AUTHOR]

Summary: The Arabidopsis gene RESISTANCE TO POWDERY MILDEW8.1 (RPW8.1) confers resistance to virulent fungal and oomycete pathogens that cause powdery mildew and downy mildew, respectively. However, the underlying mechanism remains unclear. Here, we show that ectopic expression of RPW8.1 boosts pattern‐triggered immunity (PTI) resulting in enhanced resistance against different pathogens in both Arabidopsis and rice. In Arabidopsis, transcriptome analysis revealed that ectopic expression of RPW8.1‐YFP constitutively up‐regulates expression of many pathogen‐associated molecular pattern (PAMP‐)‐inducible genes. Consistently, upon PAMP application, the transgenic line expressing RPW8.1‐YFP exhibited more pronounced PTI responses such as callose deposition, production of reactive oxygen species, expression of defence‐related genes and hypersensitive response‐like cell death. Accordingly, the growth of a virulent bacterial pathogen was significantly inhibited in the transgenic lines expressing RPW8.1‐YFP. Conversely, impairment of the PTI signalling pathway from PAMP cognition to the immediate downstream relay of phosphorylation abolished or significantly compromised RPW8.1‐boosted PTI responses. In rice, heterologous expression of RPW8.1‐YFP also led to enhanced resistance to the blast fungus Pyricularia oryzae (syn. Magnaporthe oryzae) and the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo). Taken together, our data suggest a surprising mechanistic connection between RPW8.1 function and PTI, and demonstrate the potential of RPW8.1 as a transgene for engineering disease resistance across wide taxonomic lineages of plants. [ABSTRACT FROM AUTHOR]

Villosiclava virens (Vv) is an ascomycete fungal pathogen that causes false smut disease in rice. Recent reports have revealed some interesting aspects of the enigmatic pathogen to address the question of why it specifically infects rice flowers and converts a grain into a false smut ball. Comparative and functional genomics have suggested specific adaptation of Vv in the colonization of rice flowers. Anatomical studies have disclosed that Vv specifically infects rice stamen filaments before heading and intercepts seed formation. In addition, Vv can occupy the whole inner space of a spikelet embracing all floral organs and activate the rice grain-filling network, presumably for nutrient acquisition to support the development of the false smut ball. This profile provides a general overview of the rice false smut pathogen, and summarizes advances in the Vv life cycle, genomics and genetics, and the molecular Vv-rice interaction. Current understandings of the Vv-rice pathosystem indicate that it is a unique and interesting system which can enrich the study of plant-pathogen interactions. Taxonomy: Ustilaginoidea virens is the anamorph form of the pathogen (Kingdom Fungi; Phylum Ascomycota; Class Ascomycetes; Subclass Incertae sedis; Order Incertae sedis; Family Incertae sedis; Genus Ustilaginoidea). The teleomorph form is Villosiclava virens (Kingdom Fungi; Phylum Ascomycota; Class Ascomycetes; Subclass Sordariomycetes; Order Hypocreales; Family Clavicipitaceae; Genus Villosiclava). Disease symptoms: The only visible symptom is the replacement of rice grains by ball-shaped fungal mycelia, namely false smut balls. When maturing, the false smut ball is covered with powdery chlamydospores, and the colour changes to yellowish, yellowish orange, green, olive green and, finally, to greenish black. Sclerotia are often formed on the false smut balls in autumn. Identification and detection: Vv conidia are round to elliptical, measuring 3-5 μm in diameter. Chlamydospores are ornamented with prominent irregularly curved spines, which are 200-500 nm in length. The sclerotia are black, horseshoe-shaped and irregular oblong or flat, ranging from 2 to 20 mm. Nested polymerase chain reaction (PCR) and quantitative PCR have been developed to specifically detect Vv presence in rice tissues and other biotic and abiotic samples in fields. Host range: Rice is the primary host for Vv. Natural infection by Vv has been found on several paddy field weeds, including Digitaria marginata, Panicum trypheron, Echinochloa crusgalli and Imperata cylindrica. However, the occurrence of infection in these potential alternative hosts is very rare. Life cycle: Vv infects rice spikelets at the late rice booting stage, and produces false smut balls covered with dark-green chlamydospores. Occasionally, sclerotia form on the surface of false smut balls in late autumn when the temperature fluctuates greatly between day and night. Both chlamydospores and sclerotia may serve as primary infection sources. Rainfall at the rice booting stage is a major environmental factor resulting in epidemics of rice false smut disease. Disease control: The use of fungicides is the major approach for the control of Vv. Several fungicides, such as cuproxat SC, copper oxychloride, tebuconazole, propiconazole, difenoconazole and validamycin, are often applied. However, the employment of resistant rice cultivars and genes has been limited, because of the poor understanding of rice resistance to Vv. Useful websites: Villosiclava virens genome sequence: [ABSTRACT FROM AUTHOR]

Plants have evolved a sophisticated immune system to fight against pathogenic microbes. Upon detection of pathogen invasion by immune receptors, the immune system is turned on, resulting in production of antimicrobial molecules including pathogenesis-related (PR) proteins. Conceivably, an efficient immune response depends on the capacity of the plant cell's protein/membrane trafficking network to deploy the right defense-associated molecules in the right place at the right time. Recent research in this area shows that while the abundance of cell surface immune receptors is regulated by endocytosis, many intracellular immune receptors, when activated, are partitioned between the cytoplasm and the nucleus for induction of defense genes and activation of programmed cell death, respectively. Vesicle transport is an essential process for secretion of PR proteins to the apoplastic space and targeting of defense-related proteins to the plasma membrane or other endomembrane compartments. In this review, we discuss the various aspects of protein trafficking during plant immunity, with a focus on the immunity proteins on the move and the major components of the trafficking machineries engaged. [ABSTRACT FROM AUTHOR]

Rice false smut has become an increasingly serious disease in rice ( Oryza sativa L.) production worldwide. The typical feature of this disease is that the fungal pathogen Ustilaginoidea virens ( Uv) specifically infects rice flower and forms false smut ball, the ustiloxin-containing ball-like fungal colony, of which the size is usually several times larger than that of a mature rice seed. However, the underlying mechanisms of Uv-rice interaction are poorly understood. Here, we applied time-course microscopic and transcriptional approaches to investigate rice responses to Uv infection. The results demonstrated that the flower-opening process and expression of associated transcription factors, including ARF6 and ARF8, were inhibited in Uv-infected spikelets. The ovaries in infected spikelets were interrupted in fertilization and thus were unable to set seeds. However, a number of grain-filling-related genes, including seed storage protein genes, starch anabolism genes and endosperm-specific transcription factors (RISBZ1 and RPBF), were highly transcribed as if the ovaries were fertilized. In addition, critical defense-related genes like NPR1 and PR1 were downregulated by Uv infection. Our data imply that Uv may hijack host nutrient reservoir by activation of the grain-filling network because of growth and formation of false smut balls. [ABSTRACT FROM AUTHOR]

Background The need for new effective Helicobacter pylori eradication therapy has focused efforts on the development and optimization of regimens with excellent eradication rates such as 14-day hybrid therapy. This study evaluated whether the duration of hybrid therapy could be reduced while maintaining a high eradication rate and to examine the effect of antibiotic resistance on outcome. Materials and Methods Three separate multicenter pilot studies were carried out concurrently. To reduce selection bias, eligible subjects were randomized to 10-day, 12-day, or 14-day hybrid therapy consisting of esomeprazole 40 mg and amoxicillin 1 gm twice daily for 10, 12, or 14 days plus clarithromycin 500 mg, and metronidazole 500 mg twice daily for the final 7 days. The primary outcome was H. pylori eradication per-protocol assessed at least 8 weeks after therapy. Results A total of 220 subjects were entered. The per-protocol analyses contained 60, 61, 61 subjects in the 10-, 12- and 14-day therapy studies, respectively. The eradication rates, per-protocol, were similar: 95% (95% confidence interval ( CI); 89.5-100%) for 10-day, 95.1% (95% CI; 89.7-100%) for 12-day, and 93.4% (95% CI; 87.2-99.7%) for 14-day hybrid therapies. Antibiotic resistance was infrequent; however, all metronidazole or clarithromycin resistances were cured with 12- and 14-day therapies. Conclusion These results suggest that in regions of moderate to low clarithromycin and/or metronidazole resistance it may be feasible to shorten hybrid therapy to 10 or 12 days. Further study is needed to compare hybrid and concomitant therapy in regions with moderate-to-high clarithromycin and/or metronidazole resistance. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this prospective study was to compare the efficacy of the first-line lansoprazole-based sequential therapy and concomitant therapy (lansoprazole, amoxicillin, clarithromycin and metronidazole) for Helicobacter pylori (H. pylori) eradication. METHODS: A total of 169 patients with H. pylori infection were randomly assigned to either the sequential therapy group ( n = 85) or the concomitant therapy group ( n = 84). A follow-up endoscopy or urea breath test was examined at least 12 weeks after eradication. RESULTS: Comparable H. pylori eradication rate was observed in both the sequential therapy and concomitant therapy groups by either intention-to-treat analysis [sequential 80.0% (68/85) vs concomitant 88.1% (74/84); P = 0.27] or per protocol analysis [sequential, 85.3% (64/75) vs concomitant, 94.6% (70/74); P = 0.60]. Adverse effects were reported and good compliance was observed in both groups ( P = 0.72). Although dual antibiotics resistance affected the therapeutic efficacy of sequential therapy ( P = 0.03), not concomitant therapy ( P = 0.74), it was not an independent factor for predicting the treatment outcome. CONCLUSION: First-line lansoprazole-based sequential and concomitant therapy were well-tolerated and comparable in terms of their H. pylori eradication rate. [ABSTRACT FROM AUTHOR]

Objectives: The prospective study was designed to clarify the impact of CYP2C19 on quadruple therapies and survey the efficacies of rabeprazole-based quadruple therapy for Helicobacter pylori infection after failure of standard triple therapies., Patients and Methods: From January 2007 to March 2009, 1055 H. pylori-infected patients received standard triple regimens (proton-pump inhibitor (PPI), clarithromycin, and amoxicillin). Helicobacter pylori eradication was achieved in 865 (81.9%) subjects. One hundred ninety eradication-failure patients were enrolled and randomly assigned to receive a 7-day eradication therapy. Ninety-six patients were treated with esomeprazole-based quadruple rescue therapies (EB), while 94 patients were treated with rabeprazole-based quadruple rescue therapies (RB). Follow-up endoscopy was done 16 weeks later to assess the treatment response. Patients' responses, CYP2C19 genotypes, and antibiotics resistances were also examined., Results: Intention-to-treat analysis revealed that RB had better eradication rates than EB (EB: 72.9%; 95% CI: 64.9-80.9% and RB: 78.7%; 95% CI 72.5-84.9%) (p value = .543). Per-protocol results were EB = 75.3%; 95% CI: 70.3-80.3% and RB = 85.1%; 95% CI: 80.6-89.6% (p value = .0401). Both regimens had similar compliance (p value = 0.155) and adverse events (p value = 0.219). We also surveyed those patients without resistance of any antibiotics. RB still showed better outcome than EB. Our data showed that esomeprazole-based regimen and CYP2C19 Hom EM genotype were important predictors for eradication failure., Conclusions: In quadruple therapy, rabeprazole-based regimens had better efficacy than esomeprazole-based regimens. CYP2C19 polymorphism also played an important role in quadruple therapy. It seems advisable to change PPI to rabeprazole in second-line quadruple therapy.

Background: Different kinds of proton pump inhibitor-based triple therapies could result in different Helicobacter pylori eradication rates., Aim: The aims of this study were to compare the efficacy and safety of rabeprazole- and esomeprazole-based triple therapy in primary treatment of H. pylori infection in Taiwan., Patients and Methods: From June 2005 to March 2007, 420 H. pylori-infected patients were randomly assigned to receive a 7-day eradication therapy with either esomeprazole 40 mg daily (EAC group, n = 209) or rabeprazole 20 mg b.i.d. (RAC group, n = 211) in combination with amoxicillin 1 g b.i.d. and clarithromycin 500 mg b.i.d.. Follow-up endoscopy with biopsy was done 12-16 weeks after completion of eradication therapy. Those who refused endoscopic exams underwent (13)C-urea breath test to assess the treatment response., Results: Intention-to-treat analysis revealed that the eradication rate was 89.4% in the EAC group and 90.5% in RAC groups (p-value = .72). All of the subjects returned for assessment of compliance (100% in EAC group vs. 99.5% in RAC group, p-value = .32) and adverse events (3.83% in EAC group vs. 6.16% in RAC group, p-value = .27). Sixty (28.7%) and 37 (17.6%) patients in EAC and RAC group, respectively, refused endoscopy and underwent a (13)C-urea breath test to determine the treatment effect., Conclusion: In conclusion, rabeprazole- and esomeprazole-based primary therapies for H. pylori infection are comparable in efficacy and safety.