The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro / 中西医结合学报

OBJECTIVE@#JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis.@*METHODS@#HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 μmol/L) or JZ-1 (0.078125-50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay.@*RESULTS@#HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1β (P < 0.001), and IL-18 levels (P < 0.001).@*CONCLUSION@#JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1. Please cite this article as: Liu T, Shao QQ, Wang WJ, Liu TL, Jin XM, Xu LJ, Huang GY, Chen Z. The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro. J Integr Med. 2023; 21(3): 277-288.

Parálisis facial neonatal: identificación del virus del herpes simple 1 en el líquido cefalorraquídeo. Caso clínico / Neonatal facial palsy: Identification of herpes simplex virus 1 in cerebrospinal fluid. Case report

En los neonatos, la parálisis facial es muy infrecuente y, por lo general, diagnosticada al nacer. Se presenta el primer caso de parálisis facial neonatal con identificación del virus del herpes simple 1 en el líquido cefalorraquídeo. Un varón de 35 días de vida acudió a Urgencias por la desviación de la comisura bucal hacia la izquierda y la ausencia de cierre del ojo derecho, sin sintomatología infecciosa ni antecedentes relevantes. La exploración física fue compatible con parálisis facial periférica. Las exploraciones complementarias de urgencia (hemograma, bioquímica, coagulación y citoquímica de líquido cefalorraquídeo) fueron normales. Fue ingresado con prednisolona oral y aciclovir intravenoso. La resonancia magnética craneal fue normal. A las 48 horas, se recibió el resultado positivo de la reacción en cadena de la polimerasa para el virus del herpes simple 1 en el líquido cefalorraquídeo. Con evolución favorable, completó 7 días de prednisolona oral y fue dado de alta tras 21 días de aciclovir intravenoso, con exploración neurológica previa normal.

Neonatal facial palsy is very uncommon and is generally diagnosed at birth. We present the first published case of neonatal facial palsy with identification of herpes simplex virus 1 in cerebrospinal fluid. A 35-day-old male was presented at the Emergency Department with mouth deviation to the left and impossibility of full closure of the right eye. There were no symptoms of infection or relevant medical history. Physical examination was compatible with peripheral facial palsy. Studies performed at admission were normal (blood count, biochemical analysis and coagulation blood tests and cerebrospinal fluid analysis). The patient was admitted on oral prednisolone and intravenous aciclovir. Cranial magnetic resonance was normal. Polymerase chain reaction test for herpes simplex virus 1 in cerebrospinal fluid was reported positive after 48 hours of admission. Patient followed good evolution and received prednisolone for 7 days and acyclovir for 21 days. At discharge, neurological examination was normal.

Eritema multiforme (polimorfo). puesta al día del tema: presentación de tres casos desencadenados por infección con herpes virus simple / Erythema multiforme (polymorph). updating the topic: presentation of three cases triggered by infection with herpes virus simple

El Eritema Multiforme (EM) es una reacción poco común, aguda, de piel y mucosa. Es una reacción de hipersensibilidad, caracterizada por erupciones en piel en forma de diana, constituidas por zonas concéntricas de diferente coloración, y lesiones ulcerosas o vesículo-ampollares en mucosa. La enfermedad puede ser desencadenada por infecciones, principalmente por virus del herpes simple (HSV) y Mycoplasma pneumoniae y por ingestión de drogas, siendo las más frecuentes las sulfonamidas y las penicilinas. Se presentan tres casos relacionados a la infección por el virus del herpes simple.

Erythema multiforme (EM) is a condition acute, mucocutaneous, caused by hypersensitivity reaction, characterized by skin eruption (target lesions with concentric zones) and mucous membrane lesions (ulcerous, bullous-vesicular lesions). The disorder can be induced by infections, particularly herpes simplex(VSH) and Mycoplasma pneumoniae, or by drug intake (AINE, sulfonamides, penicillin’s) Three cases related to VHS infection, are presented.

Enfermedad de Mucha-Habermann febril ulceronecrótica con respuesta favorable a minociclina, a propósito de un caso / Febrile ulceronecrotic Mucha-Habermann disease: report of one case

Pityriasis lichenoides et varioliformis acuta (PLEVA), pityriasis lichenoides chronica (PLC) and febrile ulceronecrotic Mucha-Habermann disease (FUMHD) are considered different manifestations of the same disease. Febrile ulceronecrotic Mucha-Habermann disease is a rare, and potentially lethal illness which is characterized by fast progression of numerous papules that converge, ulcerate and form a plaque with a necrotic center, together with hemorrhagic vesicles and pustules that are associated with high fever and variable systemic symptoms. We report a 16 years old male presenting with erythematous papules with crusts and fever. The diagnosis of febrile ulceronecrotic Mucha-Habermann disease was confirmed with the pathological study of the lesions. He was successfully treated with minocycline after a failed attempt of treatment with prednisone.

Cutaneous neonatal herpes simplex virus infection type 2: a case report

Abstract Neonatal herpes is a serious condition. Newborns can be contaminated in utero via transplacental hematogenic transmission, upon delivery (the most frequent route), or during the postnatal period (indirect transmission). Optimal management requires prompt and accurate recognition, particularly in newborns, in order to prevent complications. Acyclovir is the treatment of choice, but its implementation is often delayed while awaiting test results, such as PCR and serology. Cytology for diagnostic purposes is rarely used in dermatology, despite the quick and reliable results. We report a case of neonatal herpes caused by type 2 herpes simplex virus diagnosed by cytology.

Rabdomiólisis grave secundaria a deshidratación hipernatrémica / Severe rhabdomyolysis secondary to severe hypernatraemic dehydration

Introducción: La rabdomiólisis es una enfermedad poco frecuente en pediatría. El objetivo es presentar un paciente en el que se desarrolló secundario a una deshidratación hipernatrémica grave tras una diarrea aguda. Caso clínico: Lactante de 11 meses que consultó por fiebre, vómitos, diarrea y anuria. Presentó convulsión tónico-clónica autolimitada. Ingresó en mal estado general, severamente deshidratado, con escasa reactividad. En las pruebas complementarias destacó acidosis metabólica grave, hipernatremia e insuficiencia renal prerrenal. Al tercer día apreció leve hipotonía axial y elevación de creatín fosfokinasa 75.076 UI/l, interpretado como rabdomiólisis. Se inició hiperhidratación y alcalinización sistémica, con buena respuesta clínica y bioquímica, siendo dado de alta sin secuelas motoras. Conclusiones: La hipernatremia grave está descrita como causa rara de rabdomiólisis e insuficiencia renal. En pacientes críticos es importante un alto índice de sospecha de rabdomiólisis y determinación seriada de la creatín fosfokinasa para su detección y tratamiento precoz.

Introduction: Rhabdomyolysis is a rare paediatric condition. The case is presented of a patient in whom this developed secondary to severe hypernatraemic dehydration following acute diarrhoea. Case report: Infant 11 months of age who presented with vomiting, fever, diarrhoea and anuria for 15 hours. Parents reported adequate preparation of artificial formula and oral rehydration solution. He was admitted with malaise, severe dehydration signs and symptoms, cyanosis, and low reactivity. The laboratory tests highlighted severe metabolic acidosis, hypernatraemia and pre-renal kidney failure (Sodium [Na] plasma 181 mEq/L, urine density> 1030). He was managed in Intensive Care Unit with gradual clinical and renal function improvement. On the third day, slight axial hypotonia and elevated cell lysis enzymes (creatine phosphokinase 75,076 IU/L) were observed, interpreted as rhabdomyolysis. He was treated with intravenous rehydration up to 1.5 times the basal requirements, and he showed a good clinical and biochemical response, being discharged 12 days after admission without motor sequelae. Conclusions: Severe hypernatraemia is described as a rare cause of rhabdomyolysis and renal failure. In critically ill patients, it is important to have a high index of suspicion for rhabdomyolysis and performing serial determinations of creatine phosphokinase for early detection and treatment.

Bilateral lineal endotheliitis: case report / Endotelite linear bilateral: relato de caso

To report the case of a patient with bilateral herpetic lineal endotheliitis successfully treated with topic steroids and systemic antiviral. 17 year old female with blurred vision, at evaluation localized edema was observed on both corneas associated to Descemet folds and a line of pigmented precipitates. Topic prednisolone and oral acyclovir are initiated with complete resolution of signs and symptoms. Lineal endotheliitis is produced as an answer of endotelial cells to viral infection; maybe due to an immune reaction against some antigens from herpes virus family. It has the potential of relapses even in the absence of viral replication, with secondary untreatable stromal edema. It responds well to antiviral and steroids treatment, although, on those patients who don't improve, is necesary to make additional tests.

Relatar o caso de uma paciente com endotelite linear herpética bilateral tratado com sucesso por meio de corticoides tópicos e antivirais sistêmicos. Paciente do sexo feminino, 17 anos de idade, com a visão turva, na avaliação foi observado edema localizado em ambas as córneas associadas a dobras de Descemet e uma linha de precipitados ceráticos pigmentados. Prednisolona tópica e aciclovir oral foram utilizados com resolução completa dos sinais e sintomas. A endotelite linear é uma resposta das células endoteliais à infecção viral, talvez devido a uma reação imunológica contra alguns antígenos do vírus da família do herpes. Tem o potencial de recidiva, mesmo na ausência de replicação viral, com edema estromal secundário intratável. Ela responde bem ao tratamento antiviral e esteroides, embora, em pacientes que não melhoram, é necessária a realização de testes adicionais.

Inhibitory activity of Avicennia marina, a medicinal plant in Persian folk medicine, against HIV and HSV

Avicennia marina [Avicenniaceae] is a species of mangrove tree used for treatment of small pox lesions in Persian folk medicine. The antiviral activity of methanol, ethanol, water, chloroform and n-hexane extracts was evaluated against HIV-1 and HSV. Methanol extract had the highest antiviral activity and the most polar fraction of this extract [fraction D] inhibited HSV with TI and SI values of 57.1 and 133; however, it showed mild activity against HIV with SI value of 6.25 [fraction 3]. The anti-HSV activity of active fraction was confirmed using FLASH-PCR. Phytochemical investigation revealed that fraction D encompasses flavonoids compounds. The time-of-addition study demonstrated that fraction D disturbs viral replication after penetrating to the cell. A. marina was endowed with fragments by which found to be able to inhibit replication of HSV after entry but did not show significant potency against HIV-1. This promotes further investigation in anti-HSV drug discovery

Doença de Mucha-Habermann úlceronecrótica febril em adulto com boa resposta à corticoterapia oral / Febrile ulceronecrotic Mucha-Habermann disease in adult patient successfully treated with systemic corticosteroid

A doença de Mucha-Habermann ulceronecrótica febril (FUMHD) é uma variante clínica rara da pitiríase liquenoide variceliforme aguda (PLEVA). Tem etiologia incerta e é caracterizada por lesões úlceronecróticas, associadas a sintomas sistêmicos. Relata-se um caso de paciente masculino, com início agudo de lesões máculo-papulares, vesicobolhosas e úlceronecróticas, associadas à febre alta e mialgia. Tratado com prednisona 0,5 mg/kg/dia, obteve-se excelente resposta terapêutica. A FUMHD é uma variante severa da PLEVA, cujo diagnóstico é clínico e histopatológico. Vários tratamentos são descritos, tais como: metrotexate, corticoesteroides, PUVA, mas nenhum foi estabelecido.

The Febrile Ulceronecrotic Mucha-Habermann (FUMHD) disease is a rare variant of pityriasis lichenoides et varioliformis acuta (PLEVA). Its etiology still remains unknown and it is characterized by a sudden onset of ulceronecrotic skin lesions associated with systemic symptons. It is reported here the case of a male patient with a sudden and acute evolution of macules and papules, ulceronecrotic and vesicle-bullous lesions associated with systemic symptons. The patient was treated with prednisone 0,5 mg/kg/day with a dramatic response. The FUMHD is a severe variant of PLEVA and its diagnosis is clinical and histopathological. Many treatments such as methotrexate, corticosteroids and PUVA have been described .However, none of them has been settled.

Herpes simplex neonatal recorrente: relato de caso / Neonatal recurrent Herpes simplex

Descrever um recém-nascido (RN) com Herpes simplex congênito recidivante, doença de alta morbimortalidade neonatal, principalmente se o sistema nervoso central (SNC) for acometido. A transmissão vertical ocorre principalmente em infecção primária materna. Além do SNC, a manifestação clínica pode ser localizada na pele e mucosas ou com infecção sistêmica (acometimento de múltiplos órgãos). Descrição: trata-se de recém-nascido de mãe com herpes genital e portadora do HIV, condições desconhecidas ao parto. Evoluiu com lesões cutâneas e encefalite na primeira manifestação do herpes. Foi tratado com aciclovir endovenoso por 28 dias. Posteriormente, apresentou duas recidivas cutâneas, novamente tratadas. Optou-se por profilaxia com aciclovir oral, que foi mantido até a criança completar um ano. Conclusão: a literatura descreve a importância do diagnóstico, prevenção e tratamento precoces do herpes materno, prevenindo ou reduzindo a morbidade para o RN, principalmente do SNC. O uso de aciclovir oral profilático não é bem estabelecido, mas foi eficaz nesse caso.

Describe a newborn with recurrent congenital herpes, disease with high mortality and morbidity, mainly when central nervous system is involved (CNS). Vertical transmission occurs mainly in primary maternal infection. Beyond CNS, clinical manifestations can be cutaneus and disseminated infection (multiple organs disease). Description: Newborn whose mother had genital herpes not diagnosed at labor. He presented cutaneous lesions and encephalitis at the first manifestation of herpes. Treatment was performed with endovenous acyclovir during 28 days. Thereupon, he had skin lesions that recurred twice, requiring new treatments. Prophylaxis with oral acyclovir was introduced and prescribed until the children attained one year old. Comments: Literature recognizes the importance of early diagnosis, prevention and treatment of maternal herpes, in order to minimize mortality and morbidity for the newborn, mainly related to CNS involvement. Prophylaxis with oral aciclovir is not well defined, but was successful in this case.

Estudio del efecto inmunomodulador de la Equinácea purpúrea en pacientes con herpes labial recurrente / Imunomodulatory effects of Echinacea purpurea in patients with recurrent herpes labialis

Introducción: El Herpes Labial Recurrente supone una condición inmunológica alterada, tal como una hiperactividad de células T-reguladoras CD4+CD25+ (Treg). Éstas ejercen control sobre la tolerancia periférica y reducen el riesgo inmunopatológico, suprimiendo otras líneas celulares. Por ende, la supresión ejercida sobre la reacción inmune antiviral podría afectar negativamente el curso de la infección. Este contexto ha impulsado la búsqueda de nuevas alternativas inmunomoduladoras como la Equinácea purpúrea. Dada su propiedad inmunosupresora, se propone en el tratamiento del Herpes Labial Recurrente. Metodología: Estudio clínico prospectivo que analiza las subpoblaciones linfocitarias en 12 pacientes con Herpes Labial Recurrente, antes y después de recibir Equinácea purpúrea (30 gotas tres veces al día durante siete días).Resultados: En comparación con individuos sanos, los pacientes presentan una respuesta aumentada de células Treg. Esta condición se reduce significativamente tras recibir Equinácea purpúrea (515 + 145 y 432 + 113 cel/mm3 antes y después del tratamiento, respectivamente, p < 0,005). Conclusión: La hiperactividad de células Treg podría explicar el estado de inmunosupresión de estos pacientes y favorecería la persistencia viral. Se propone esta fitomedicina como una alternativa inmunoterapéutica beneficiosa.

Background: Recurrent Herpes Labialis patients may suffer from immunological alterations, such as CD4+CD25+Regulatory-T Cell (Treg) hyperactivity. These cells control peripheral tolerance and reduce immunopathology risk by suppressing other immunological cells. Hence, the Treg cell suppression on the antiviral immune reaction may perturb adversely the herpes infection outcome. This scenario has forced physicians to explore new immunomodulatory alternatives in Phytomedicine, such as Echinacea purpurea. Regarding the immunosuppressive property, it has been challenged to be employed in the Recurrent Herpes Labialis management. Methods: Clinical prospective study that analyzed lymphocytic subpopulation profile in twelve patients with Recurrent Herpes Labialis, before and after receiving E. purpurea (30 drops three times a day during seven days). Results: Comparing to healthy subjects, patients presented an enlarged Treg cell response. This condition became significantly reduced after receiving E. purpurea. (515 + 145 and 432 + 113 cel, before and after treatment respectively, p < 0.005). Conclusion: The intensified Treg cell activity may elucidate the immune suppression these patients undergo, aiding the viral persistence and survival. This proposes E. purpurea asa beneficial immunotherapeutic alternative.

Uso del Interferón Alfa en enfermedades virales por vía tópica / The usage of topic Alfa interferon in viral diseases

El Interferón es un conjunto de proteínas que se producen principalmente frente a un estímulo viral, también favorece y promueve otros mecanismos inmunológicos por lo cual es considerado una Citoquina, siendo el uso más frecuente, el terapéutico, en aquellas enfermedades donde se sospeche un origen principalmente viral. Desde su descubrimiento en el año 1957, el uso terapéutico es en afecciones las cuales se sospeche un origen viral y el cáncer, siendo más limitado su empleo como estimulador del Sistema Inmunológico. En el presente trabajo hemos tomado un grupo de estudio constituido por 362 pacientes al cual se le aplicó el Interferòn por vía tópica comparado con un Grupo control formado por 343 pacientes tratados con la terapéutica convencional durante 10 años de tratamiento. A ambos grupos se les habían diagnosticado diversas afecciones Virales de Piel y Mucosas y fueron tratados por un espacio de 10 años, tomándose una muestra inicial antes del tratamiento y posterior al mismo con intervalos de 1, 3, 6,12 meses y a los dos años de iniciado el tratamiento, comparándose algunos parámetros de la respuesta inmunológica, detectándose posteriormente en el grupo de estudio un aumento de la Inmunidad Humoral Sistémica, una remisión de los síntomas de más de 6 años y pocas reacciones colaterales.

The Interferon is a group of proteins, produced mainly against a viral stimulus; it also favors and promotes other immunologic mechanisms and that is why it is considered a cytokine, being its most frequent use, therapeutic, mainly in diseases of suspected viral origin. Since it was discovered in 1957, it has been therapeutically used in affections of suspected viral origins and cancer, being more limitedly used as a stimulator of the Immunological System. In our work we had a study group composed by 362 patients, who received Interferon by topical way, compared to a control group of 343 patients treated with conventional therapy during 10 years. Both groups were diagnosed with various viral affections of the skin and the mucous membrane. They were treated during 10 years, taking a sample before the treatment began and at the end of the 1 st , 3 rd , 6 th , 12 th months and the 2 nd year after the beginning of the treatment. Some parameters of the immunologic answer were compared, detecting in the study group an increase of the Systemic Humoral Immunity, a remission of the more-than-6-years symptoms and few side effects.