Effect of platelet-rich plasma on healing of lower extremity diabetic skin ulcers: A meta-analysis.

The aim of this research is to explore the therapeutic efficacy of platelet-rich plasma (PRP) on the cutaneous ulceration of diabetes mellitus (DM). From the beginning of the database until January 2024, we looked through several databases to obtain randomised, controlled PRP studies to treat the wound healing of DM in adult patients. The Cochrane Collaboration's Risk-Of-Bias Instrument was used to evaluate the risk of bias in randomised, controlled studies. Funnel plots, sensitivity analyses and Egger regression tests were employed to determine the reliability and effectiveness of the meta-analyses. Depending on the degree of heterogeneity, a fixed or random effect model has been used. The statistical significance was determined to be below 0.05. Altogether 281 trials were collected from the database and entered into Endnote Software for screening, and 15 trials were analysed. It was found that PRP was associated with a higher rate of wound healing (OR, 3.23; 95% CI, 2.42, 4.31 p < 0.0001). PRP was associated with a reduction in the risk of post-operative wound infection (OR, 0.46; 95% CI, 0.21, 0.99 p = 0.05). PRP was associated with a reduction in the risk of amputations amongst those with DM (OR, 0.50; 95% CI, 0.30, 0.84 p = 0.009). Overall, PRP treatment for DM is expected to improve the rate of wound healing, decrease the risk of wound infection and decrease the risk of amputations.

The value of platelet-rich plasma-derived extracellular vesicles in modern medicine.

Platelet-rich plasma (PRP) has been widely used in clinical practice. The mechanism by which PRP promotes tissue repair lies in the release of multiple growth factors upon platelet activation, which accelerates the proliferation and differentiation of repair cells and the synthesis of extracellular matrix. In recent years, as extracellular vesicles (EVs) research has increased and intensified, it has been found that EVs also play an important role in tissue repair. This article provides a comprehensive review of the role of PRP and PRP-derived extracellular vesicles (PRP-EVs) in tissue repair. It discusses the biological characteristics, extraction, identification, activation, and preservation of PRP-EVs. It also reviews their applications in orthopedics and wound repair. The article highlights the importance of PRP-EVs in modern medicine and suggests that they could be a promising natural nanocarrier.

The review discusses extracellular vesicles derived from platelet-rich plasma(PRP-EVs). PRP promotes repair of the body's tissues and has been used in clinical practice for many years. Extracellular vesicles are granules released by cells that facilitate intercellular communication. Studies in recent years have revealed that PRP can also release extracellular vesicles that participate in the repair process of tissues. Here, we elaborate on PRP-EVs. Regarding PRP-EVs, current studies are limited to the animal level and have not yet been used in the clinical setting.

A Case Report of Primary Malignant Melanoma of the Gallbladder with Multiple Metastases.

Primary malignant melanoma of the gallbladder is an extremely rare tumor with approximately 39 cases described in the literature so far. However, since the first case was reported in 1907, it remains controversial whether gallbladder involvement in malignant melanoma is primary or metastatic. Here, we report a case of primary malignant melanoma of the gallbladder. A 52-year-old male presented to the emergency department with right upper quadrant abdominal pain and was found to have tumefactive sludge filling the majority of the gallbladder with possible gallbladder wall thickening on ultrasonography. A laparoscopic cholecystectomy was performed for presumed acute cholecystitis. Histopathologic examination of the gallbladder revealed malignant melanoma arising from the mucosa of the gallbladder. Further clinical investigation excluded other primary sites, supporting a diagnosis of primary malignant melanoma of the gallbladder.

LINC00969 inhibits proliferation with metastasis of breast cancer by regulating phosphorylation of PI3K/AKT and ILP2 expression through HOXD8.

Background: Breast cancer (BC) is a malignancy that is inadequately treated and poses a significant global health threat to females. The aberrant expression of long noncoding RNAs (lncRNAs) acts as a complex with a precise regulatory role in BC progression. LINC00969 has been linked to pyroptotic cell death and resistance to gefitinib in lung cancer cells. However, the precise function and regulatory mechanisms of LINC00969 in BC remain largely unexplored. Methods: Cell proliferation, migration, and invasion of BC cells were evaluated using CCK-8 and Transwell assays. Western blotting was employed to analyze the protein expression levels of HOXD8, ILP2, PI3K, t-AKT, and p-AKT. Results: LINC00969 was drastically reduced in BC tissues LINC00969 overexpression markedly suppressed proliferation, migration, and invasion, and blocked PI3K and p-AKT protein expression in MCF-7 cells. Activation of the PI3K/AKT pathway reversed the suppressive effect of LINC0096 overexpression on the proliferation, migration, and invasion of MCF-7 cells. Moreover, LINC00969 overexpression enhanced HOXD8 and blocked ILP2 protein expression in MCF-7 cells. In contrast, activating the PI3K/AKT pathway had no effect on HOXD8 and blocked ILP2 protein expression in MCF-7 cells overexpressing LINC00969. HOXD8 knockdown enhanced ILP2, PI3K, and p-AKT protein expression, and the proliferation, migration, and invasion of MCF-7 cells co-transfected with si-HOXD8 and ov-LINC00969. LINC00969 regulated HOXD8 via binding to miR-425-5p. Conclusion: LINC00969 inhibits the proliferation and metastasis of BC cells by regulating PI3K/AKT phosphorylation through HOXD8/ILP2.

Identification of the multiple roles of enolase as an plasminogen receptor and adhesin in Mycoplasma hyopneumoniae.

Mycoplasma hyopneumoniae is the etiological agent underlying porcine enzootic pneumonia, a chronic respiratory disease worldwide. The recruitment of plasminogen to the surface and subsequently promotion of plasmin conversion by the surface-located receptor, have been reported to assist the adhesion and invasion of Mycoplasmas. The surface localization and plasminogen-binding ability of M. hyopneumoniae enolase were previously confirmed; however, the biological functions were not be determined, especially the role as a plasminogen receptor. Here, using ELISA and SPR analyses, we confirmed the stable binding of M. hyopneumoniae enolase to plasminogen in a dose-dependent manner. The facilitation of the activation of plasminogen in the presence of tPA and direct activation of plasminogen at low efficiency without tPA addition by M. hyopneumoniae enolase were also determined using a plasmin-specific chromogenic substrate. Notably, the C-terminal and N-terminal regions located in M. hyopneumoniae enolase play an important role in plasminogen binding and activation. Additionally, we demonstrate that M. hyopneumoniae enolase can competitively inhibit the adherence of M. hyopneumoniae to PK15 cells. These results provide insight into the role of enolase in M. hyopneumoniae infection, a mechanism that manipulates the proteolytic system of the host.

Clinicopathologic parameters and outcomes of mucinous neoplasms confined to the appendix: a benign entity with excellent prognosis.

Appendiceal mucinous neoplasms (AMNs), characterized by expansile or "pushing" growth of neoplastic epithelium through the appendix wall, are sometimes accompanied by peritoneal involvement, the extent and grade of which largely determine clinical presentation and long-term outcomes. However, the prognosis of tumors entirely confined to the appendix is still debated and confusion remains regarding their biologic behavior and, consequently, their clinical management and even diagnostic nomenclature. We evaluated AMNs limited to the appendix from 337 patients (median age: 58 years, interquartile range (IQR): 47-67), 194 (57.6%) of whom were women and 143 (42.4%) men. The most common clinical indication for surgery was mass or mucocele, in 163 (48.4%) cases. Most cases (N = 322, 95.5%) comprised low-grade epithelium, but there were also 15 (4.5%) cases with high-grade dysplasia. Lymph nodes had been harvested in 102 (30.3%) cases with a median 6.5 lymph nodes (IQR: 2-14) per specimen for a total of 910 lymph nodes examined, all of which were negative for metastatic disease. Histologic slide review in 279 cases revealed 77 (27.6%) tumors extending to the mucosa, 101 (36.2%) to submucosa, 33 (11.8%) to muscularis propria, and 68 (24.4%) to subserosal tissues. In multivariate analysis, deeper tumor extension was associated with older age (p = 0.032; odds ratio (OR): 1.02, 95% confidence intervals (CI): 1.00-1.03), indication of mass/mucocele (p < 0.001; OR: 2.09, CI: 1.41-3.11), and wider appendiceal diameter, grossly (p < 0.001; OR: 1.61, CI: 1.28-2.02). Importantly, among 194 cases with at least 6 months of follow-up (median: 56.1 months, IQR: 24.4-98.5), including 9 high-grade, there was no disease recurrence/progression, peritoneal involvement (pseudomyxoma peritonei), or disease-specific mortality. These data reinforce the conclusion that AMNs confined to the appendix are characterized by benign biologic behavior and excellent clinical prognosis and accordingly suggest that revisions to their nomenclature and staging would be appropriate, including reverting to the diagnostic term mucinous adenoma in order to accurately describe a subset of them.

Rapid and sensitive detection of African swine fever virus in pork using recombinase aided amplification combined with QDMs-based test strip.

African swine fever virus (ASFV) is the pathogen of African swine fever, a highly contagious and fatal disease of wild boar and domestic pigs. The flow of ASFV through pork products is more concealed, higher risky, and more difficult to prevent and control. Presently, on-site ASFV detection methods in preclinical infected pigs and circulated pork products are lacking. Here, fluorescent test strip-based rapid ASFV detection method in pork was established combined with recombinase aided amplification (RAA) and quantum dot microspheres (QDMs). This method is specific to ASFV with no cross-reactivity to pseudorabies virus (PRV), porcine circovirus type 2 (PCV2), and porcine reproductive and respiratory syndrome virus (PRRSV). The method also showed highly sensitivity with a detection limit of 1 copy for ASFV plasmid templates containing B646L gene and 100 copies/g for DNA extracts from clinical pork samples within a short detection time of less than 25 min. Additionally, the method showed 99.17% consistency with real-time PCR in the ASFV detection of 120 clinical pork samples. Overall, the QDMs-based test strip method provides specific, sensitive, rapid, and simple detection of ASFV in pork, which may contribute to maintain the food safety of pork products, and facilitate ASFV traceability and prevention. Rapid and sensitive detection of African swine fever virus in pork by QDMs based test strip assay.

Intratumoral Budding and Tumor Microenvironment in Pretreatment Rectal Cancer Biopsies Predict the Response to Neoadjuvant Chemoradiotherapy.

Tumor budding at the invasive tumor front (peritumoral budding) is an established prognostic factor in colorectal cancer. However, the significance of intratumoral budding (ITB) in pretreatment biopsies is still uncertain. Our study aims to investigate the association of ITB and tumor microenvironment in pretreatment rectal cancer biopsies with pathologic response to neoadjuvant chemoradiotherapy. Pretreatment biopsies of low-grade rectal cancer from 37 patients who underwent resection after neoadjuvant chemoradiotherapy were retrospectively reviewed to evaluate ITB, type of tumor stroma, and intraepithelial lymphocytes. ITB was counted on a single hotspot in 1 HPF upon pan-keratin immunohistochemical staining. Intraepithelial lymphocytes was graded semiquantitatively as "absent" (≤2/HPF) or "present" (>2/HPF). The tumor stroma was classified as either immature type or maturing type. In pretreatment biopsies, ITB was observed in 34/37 patients (92%). High-grade ITB was significantly associated with a poor pathologic response to neoadjuvant chemoradiotherapy (tumor regression score 2 to 3, P<0.001; and higher posttreatment T stage, P=0.002). Immature type of stroma was significantly associated with both high-grade ITB in biopsies (P=0.02) and a poor pathologic response to neoadjuvant chemoradiotherapy (tumor regression score 2 to 3, P=0.005). In multivariate analysis, ITB and the type of stroma remained the significant parameters for prediction of response to neoadjuvant treatment. Our study indicates that ITB and tumor microenvironment in pretreatment biopsies are strong predictors of response to neoadjuvant chemoradiotherapy, which may assist risk stratification and clinical management in rectal cancer patients.

Overexpression of HOXD8 inhibits the proliferation, migration and invasion of breast cancer cells by downregulating ILP2 expression.

Breast cancer is one of the most common malignant tumors in women. Although a number of homeobox (HOX) genes are known to serve an important role in breast cancer, the role of HOXD8 in breast cancer remains unclear. The aim of the present study was to investigate the role of HOXD8 in the physiological behaviors of breast cancer cells. The Gene Expression Profiling Interactive Analysis database was used to analyze the expression of HOXD8 in patients with breast cancer and in healthy subjects. Western blotting was performed to determine the expression levels of HOXD8 in several breast cancer cell lines; subsequently, HOXD8 expression was knocked down and overexpressed in MCF-7 cells. Cell Counting Kit-8, colony formation, wound healing and Transwell assays were used to evaluate the effects of HOXD8 on breast cancer cell viability, proliferation, migration and invasion, respectively. Chromatin immunoprecipitation and dual-luciferase reporter assays were conducted to identify the binding sites between HOXD8 and inhibitor of apoptosis-like protein-2 (ILP2). In addition, ILP2 expression levels were knocked down in MCF-7 cells. The results demonstrated that the expression levels of HOXD8 were significantly downregulated in breast cancer tissues and cell lines, and that the overexpression of HOXD8 inhibited the proliferation, invasion and migration of cancer cells. HOXD8 was shown to bind to the ILP2 promoter to regulate the expression of ILP2. Furthermore, ILP2 knockdown reversed the effects of HOXD8 knockdown on breast cancer cell proliferation, invasion and migration. In conclusion, the findings of the present study suggested that HOXD8 may inhibit the proliferation, migration and invasion of breast cancer cells by downregulating ILP2 expression.

Recurrent loss of chromosome 22 and SMARCB1 deletion in extra-axial chordoma: A clinicopathological and molecular analysis.

Extra-axial chordoma is a rare neoplasm of extra-axial skeleton and soft tissue that shares identical histomorphologic and immunophenotypic features with midline chordoma. While genetic changes in conventional chordoma have been well-studied, the genomic alterations of extra-axial chordoma have not been reported. It is well known that conventional chordoma is a tumor with predominantly non-random copy number alterations and low mutational burden. Herein we describe the clinicopathologic and genomic characteristics of six cases of extra-axial chordoma, with genome-wide high-resolution single nucleotide polymorphism array, fluorescence in situ hybridization and targeted next-generation sequencing (NGS) analysis. The patients presented at a mean age of 33 years (range: 21-54) with a female to male ratio of 5:1. Four cases were histologically conventional type, presented with bone lesions and three of them had local recurrence. Two cases were poorly differentiated chordomas, presented with intra-articular soft tissue masses and both developed distant metastases. All cases showed brachyury positivity and the two poorly differentiated chordomas showed in addition loss of INI-1 expression by immunohistochemical analysis. Three of four extra-axial conventional chordomas showed simple genome with loss of chromosome 22 or a heterozygous deletion of SMARCB1. Both poorly differentiated chordomas demonstrated a complex hyperdiploid genomic profile with gain of multiple chromosomes and homozygous deletion of SMARCB1. Our findings show that heterozygous deletion of SMARCB1 or the loss of chromosome 22 is a consistent abnormality in extra-axial chordoma and transformation to poorly differentiated chordoma is characterized by homozygous loss of SMARCB1 associated with genomic complexity and instability such as hyperdiploidy.

Functional interaction between long non-coding RNA and microRNA in rheumatoid arthritis.

MicroRNA (miRNA) has received widespread attention for its role in several key cellular processes such as cell differentiation, cell proliferation, apoptosis, and autoimmune diseases. Although we now have a good understanding of miRNA expression and function, our knowledge regarding the molecular mechanism of long non-coding RNA (lncRNA) is still in its infancy. In this review, we will briefly introduce the definition and function of lncRNA and summarize the interactions between lncRNA and miRNA and their research progress in rheumatoid arthritis (RA). The expression of miR-16, miR-146a, miR-155, and miR-223 and the interactions between HOTAIR and miR138, ZFAS1 and miR-27a, and GAPLINC and miR-575 are representative examples that may augment the understanding of the pathogenesis of RA and help in the development of new biomarkers and target therapies.

Fifteen-Year Follow-Up of a Patient with Acinar Cystic Transformation of the Pancreas and Literature Review.

Acinar cystic transformation (ACT), also known as "acinar cell cystadenoma," is a rare and newly recognized benign pancreatic cystic neoplasm. However, its true malignant potential remains unknown. Here, we report a case of ACT with 15-year follow-up. A 10-year-old female initially presented with abdominal pain and was found to have a cystic lesion in the region of pancreatic head on computed tomography scan. She underwent an exploratory laparotomy, and the intraoperative biopsy of the cyst wall showed a true pancreatic cyst without malignancy. Her symptoms subsequently resolved, and she was placed under close ultrasound surveillance. For the next fifteen years, the patient was asymptomatic without any complications and had a successful pregnancy. Surveillance showed the tumor grew in size from 4.2 cm to 6.2 cm in diameter. In the latest five months, she noted occasional abdominal pain. A pylorus-preserving pancreaticoduodenectomy was performed. The resected cystic lesion was multilocular and lined by a single layer of bland epithelium ranging from nondescript flat/cuboidal epithelium to apparent acinar cells which were strongly positive for trypsin, so the final diagnosis was confirmed to be ACT. The prior biopsy was retrospectively reviewed to reveal similar epithelial lining. To the best of our knowledge, this is the longest period of follow-up for ACT to date. Our findings suggest that ACT is a slow-growing neoplasm without malignant transformation after fifteen years. Therefore, we recommend biopsy for histologic diagnosis followed by close ultrasound surveillance without surgical intervention in asymptomatic or young ACT patients.

Extrauterine adenomyomas presenting in a 47 year old woman with a previous cesarean section.

•Extrauterine adenomyoma cannot be solely diagnosed on the basis of radiographic appearance.•There are five theories for the pathophysiology of extrauterine adenomyomas.•Surveillance and treatment range from none to ovarian suppression.

A tyrosine-based motif in the HIV-1 envelope glycoprotein tail mediates cell-type- and Rab11-FIP1C-dependent incorporation into virions.

Lentiviruses such as HIV-1 encode envelope glycoproteins (Env) with long cytoplasmic tails (CTs) that include motifs mediating interactions with host-cell-trafficking factors. We demonstrated recently that Rab11-family interacting protein 1C (FIP1C) is required for CT-dependent incorporation of Env into HIV-1 particles. Here, we used viruses bearing targeted substitutions within CT to map the FIP1C-dependent incorporation of Env. We identified YW795 as a critical motif mediating cell-type-dependent Env incorporation. Disruption of YW795 reproduced the cell-type-dependent particle incorporation of Env that had previously been observed with large truncations of CT. A revertant virus bearing a single amino acid change near the C terminus of CT restored wild-type levels of Env incorporation, Gag-Env colocalization on the plasma membrane, and viral replication. These findings highlight the importance of YW795 in the cell-type-dependent incorporation of Env and support a model of HIV assembly in which FIP1C/RCP mediates Env trafficking to the particle assembly site.

An siRNA screen of membrane trafficking genes highlights pathways common to HIV-1 and M-PMV virus assembly and release.

The assembly and release of retroviruses from the host cells requires a coordinated series of interactions between viral structural proteins and cellular trafficking pathways. Although a number of cellular factors involved in retrovirus assembly have been identified, it is likely that retroviruses utilize additional trafficking factors to expedite their assembly and budding that have not yet been defined. We performed a screen using an siRNA library targeting host membrane trafficking genes in order to identify new host factors that contribute to retrovirus assembly or release. We utilized two retroviruses that follow very distinct assembly pathways, HIV-1 and Mason-Pfizer monkey virus (M-PMV) in order to identify host pathways that are generally applicable in retrovirus assembly versus those that are unique to HIV or M-PMV. Here we report the identification of 24 host proteins identified in the screen and subsequently validated in follow-up experiments as contributors to the assembly or release of both viruses. In addition to identifying a number of previously unsuspected individual trafficking factors, we noted multiple hits among proteins involved in modulation of the actin cytoskeleton, clathrin-mediated transport pathways, and phosphoinositide metabolism. Our study shows that distant genera of retroviruses share a number of common interaction strategies with host cell trafficking machinery, and identifies new cellular factors involved in the late stages of retroviral replication.

ROCK1 and LIM kinase modulate retrovirus particle release and cell-cell transmission events.

UNLABELLED: The assembly and release of retroviruses from the host cells require dynamic interactions between viral structural proteins and a variety of cellular factors. It has been long speculated that the actin cytoskeleton is involved in retrovirus production, and actin and actin-related proteins are enriched in HIV-1 virions. However, the specific role of actin in retrovirus assembly and release remains unknown. Here we identified LIM kinase 1 (LIMK1) as a cellular factor regulating HIV-1 and Mason-Pfizer monkey virus (M-PMV) particle release. Depletion of LIMK1 reduced not only particle output but also virus cell-cell transmission and was rescued by LIMK1 replenishment. Depletion of the upstream LIMK1 regulator ROCK1 inhibited particle release, as did a competitive peptide inhibitor of LIMK1 activity that prevented cofilin phosphorylation. Disruption of either ROCK1 or LIMK1 led to enhanced particle accumulation on the plasma membrane as revealed by total internal reflection fluorescence microscopy (TIRFM). Electron microscopy demonstrated a block to particle release, with clusters of fully mature particles on the surface of the cells. Our studies support a model in which ROCK1- and LIMK1-regulated phosphorylation of cofilin and subsequent local disruption of dynamic actin turnover play a role in retrovirus release from host cells and in cell-cell transmission events. IMPORTANCE: Viruses often interact with the cellular cytoskeletal machinery in order to deliver their components to the site of assembly and budding. This study indicates that a key regulator of actin dynamics at the plasma membrane, LIM kinase, is important for the release of viral particles for HIV as well as for particle release by a distantly related retrovirus, Mason-Pfizer monkey virus. Moreover, disruption of LIM kinase greatly diminished the spread of HIV from cell to cell. These findings suggest that LIM kinase and its dynamic modulation of the actin cytoskeleton in the cell may be an important host factor for the production, release, and transmission of retroviruses.

Direct evidence for intracellular anterograde co-transport of M-PMV Gag and Env on microtubules.

The intracellular transport of Mason-Pfizer monkey virus (M-PMV) assembled capsids from the pericentriolar region to the plasma membrane (PM) requires trafficking of envelope glycoprotein (Env) to the assembly site via the recycling endosome. However, it is unclear if Env-containing vesicles play a direct role in trafficking capsids to the PM. Using live cell microscopy, we demonstrate, for the first time, anterograde co-transport of Gag and Env. Nocodazole disruption of microtubules had differential effects on Gag and Env trafficking, with pulse-chase assays showing a delayed release of Env-deficient virions. Particle tracking demonstrated an initial loss of linear movement of GFP-tagged capsids and mCherry-tagged Env, followed by renewed movement of Gag but not Env at 4h post-treatment. Thus, while delayed capsid trafficking can occur in the absence of microtubules, efficient anterograde transport of capsids appears to be mediated by microtubule-associated Env-containing vesicles.

[Rash and fever illness caused by herpes simplex virus type 1 needs to be distinguished from hand, foot and mouth disease].

An epidemic of rash and fever illnesses suspected of hand, foot and mouth disease (HFMD) occurred in Gansu Province of China in 2008, laboratory tests were performed in order to identify the pathogen that caused this epidemic. Eight clinical specimens collected from the 4 patients (each patient has throat swab and herpes fluid specimens) with rash and febrile illness, were inoculated onto RD and HEp-2 cells for virus isolation, and the viral nucleic acid was then extracted with the positive virus isolates, the dual-channel real-time reverse transcript-polymerase chain reaction (RT-PCR) was performed to detect the nucleic acid of human enterovirus (HEV) in the viral isolates at the same time. For the viral isolates with the negative results of HEV, a sequence independent single primer amplification technique (SISPA) was used for "unknown pathogen" identification. Totally, 6 viral isolates were identified as herpes simplex virus type 1 (HSV-1). Comprehensive analyses results of the clinical manifestations of the patients, epidemiological findings and laboratory test indicated that this epidemic of rash and febrile illness was caused by HSV-1. The differences among the gG region of 6 HSV-1 isolates at nucleotide level and amino acid level were all small, and the identities were up to 98. 8% and 97.9%, respectively, showing that this outbreak was caused by only one viral transmission chain of HSV-1. HSV-1 and other viruses that cause rash and febrile illnesses need differential diagnosis with HFMD. The etiology of rash and febrile illness is sometimes difficult to distinguish from the clinical symptoms and epidemiological data, the laboratory diagnosis is therefore critical.

The HIV-1 protein Vpr targets the endoribonuclease Dicer for proteasomal degradation to boost macrophage infection.

The HIV-1 protein Vpr enhances macrophage infection, triggers G2 cell cycle arrest, and targets cells for NK-cell killing. Vpr acts through the CRL4(DCAF1) ubiquitin ligase complex to cause G2 arrest and trigger expression of NK ligands. Corresponding ubiquitination targets have not been identified. UNG2 and SMUG1 are the only known substrates for Vpr-directed depletion through CRL4(DCAF1). Here we identify the endoribonuclease Dicer as a target of HIV-1 Vpr-directed proteasomal degradation through CRL4(DCAF1). We show that HIV-1 Vpr inhibits short hairpin RNA function as expected upon reduction of Dicer levels. Dicer inhibits HIV-1 replication in T cells. We demonstrate that Dicer also restricts HIV-1 replication in human monocyte-derived macrophages (MDM) and that reducing Dicer expression in MDMs enhances HIV-1 infection in a Vpr-dependent manner. Our results support a model in which Vpr complexes with human Dicer to boost its interaction with the CRL4(DCAF1) ubiquitin ligase complex and its subsequent degradation.