Notes

[Open fractures].
The enhanced forms of fenbendazole and albendazole significantly prolonged survival in mice bearing metastases, and albendazole-treated mice displayed significantly longer median survival times than paclitaxel-treated mice. Importantly, these drugs effectively targeted taxane-resistant tumors and bone metastases - two common clinical conditions in patients with aggressive prostate cancer. In summary, we find that metastatic prostate tumor cells differ from benign prostate tumor cells in their sensitivity to certain drug classes. Taken together, our results strongly suggest that albendazole, an anthelmintic medication, may represent a potential adjuvant or neoadjuvant to standard therapy in the treatment of disseminated prostate cancer.
Mitochondria are highly dynamic organelles which remain in a continuous state of fission/ fusion dynamics to meet the metabolic needs of a cell. However, this fission/fusion dynamism has been reported to be dysregulated in most cancers. Linsitinib mw Such enhanced mitochondrial fission is demonstrated to be positively regulated by some activating oncogenic mutations; such as those of KRAS (Kristen rat sarcoma viral oncogene homologue) or BRAF (B- rapidly accelerated fibrosarcoma), thereby increasing tumor progression/ chemotherapeutic resistance and metabolic deregulation. However, the underlying mechanism(s) are still not clear, thus highlighting the need to further explore possible mechanism(s) of intervention. We sought to investigate how BRAF
driven CRC (colorectal cancer) progression is linked to mitochondrial fission/fusion dynamics and whether this window could be exploited to target CRC progression.

Western blotting was employed to study the differences in expression levels of key proteins regulating mitochonnogenic potential and metastatic advantage to cells harboring
. Interestingly, such fragmented mitochondrial state seemed positively regulated by mitochondrial
as observed through pharmacologic as well as genetic inhibition of
.

In conclusion, our data suggest that
driven colorectal cancers have fragmented mitochondria which confers glycolytic phenotype and growth advantage to these tumors, and such phenotype is dependent at least in part on
- thus highlighting a potential therapeutic target.
In conclusion, our data suggest that BRAFV600E driven colorectal cancers have fragmented mitochondria which confers glycolytic phenotype and growth advantage to these tumors, and such phenotype is dependent at least in part on PDK1- thus highlighting a potential therapeutic target.
Polychlorinated biphenyls (PCBs) are lipophilic and persistent environmental pollutants that are readily absorbed and accumulated in high concentrations in fatty tissues of humans and animals. Invertebrate animals, such as oysters, are vulnerable and sensitive to PCB contamination.

Previously, our in vitro isothermal studies have shown that acid processed montmorillonites (APM) can effectively bind PCBs and Aroclors. Therefore, in a novel application of this work, a dietary strategy for shellfish was developed using APM, and its parent clay to reduce exposures to PCBs in oysters. PCB residues in oysters with clay treatment at different dietary inclusion rates and durations were measured and compared to a washout treatment.

The efficacy and safety of this strategy were supported by a significant reduction of PCB residues with the inclusion of a low level of APM (0.05%) during a 4-day treatment. Moreover, this sorbent strategy reduced PCB residues in oysters in a dose- and time-dependent manner.

Based on our results, it is possible that clay-based sorbents such as APM, can be included in the diet to significantly reduce exposures to PCBs.
Based on our results, it is possible that clay-based sorbents such as APM, can be included in the diet to significantly reduce exposures to PCBs.
Xenograft bone scaffolds have advantages such as mechanical strength, sufficient source and safety. Combined with siRNA properly targeting CKIP-1, a negative regulator of osteogenesis, may contribute to the repair result of calcine bone alone.

Herein, we constructed a novel xenograft bovine bone scaffold namely (DSS)6-liposome/CKIP-1 siRNA/calcine bone, the characteristics of which were investigated by confirming the effect of (DSS)6-liposome, observing the appearance and testing mechanical strength of calcine bone, and observing the combined result of CKIP-1 siRNA by FAM immunofluorescence. In addition, cytotoxicity by CCK-8 and LDH activity of L929cells and MC3T3-E1 osteoblasts cultured with the scaffold were tested in vitro, primary osteoblasts proliferation, the mRNA expressions of CKIP-1, ALP, COL1-α and OCN, the protein expressions of CKIP-1, BMP-2, COL-1 and Runx2 and calcium nodules were also determined by CCK-8, RT-qPCR, western-blot and Alizarin Red staining in vitro. Then, we successively estased as a novel xenograft bone scaffold for osteogenesis with the good safety.
These findings provide evidence that (DSS)6- liposome/CKIP-1 siRNA/calcine bone could be used as a novel xenograft bone scaffold for osteogenesis with the good safety.
The purpose of this study was to evaluate the therapeutic effects and mechanism of
for the treatment of osteoarthritis (OA) in a rat model.

8-10-week-old male Sprague-Dawley rats were randomly divided into the sham group (vehicle-treated), OA group (vehicle-treated), high-dose, middle-dose, low-dose of
-treated groups. OA was induced by transecting the medial collateral ligament and the medial meniscus in the right limb. The Sprague-Dawley rats were treated daily for 12 weeks with different concentrations of
low (QFZT-L, 128mg/kg), medium (QFZT-M, 256.5mg/kg), and high (QFZT-H, 513mg/kg) by gavage administration for a period of 4 and 12 weeks respectively. Vehicle-treated rats served as controls and administered 0.5% Carboxymethyl Cellulose Sodium (CMC-Na) by gavage on the same schedule. Weekly measurement of dynamic weight-bearing capacity, grip strength, joint swelling was were performed to monitor the progression of disease for 3 weeks. After euthanasia, the knee joints were articular cartilZT groups.

In a rat model of OA,
shows the tendency to reduce the destruction of cartilage, joint swelling and bone erosion which provides new evidence for the therapeutic potential of
in the treatment of OA in clinics.

The QFZT capsule can improve the symptoms of the OA in rodent animal rats by attenuating pain and retarding cartilage damage. This study indicated that the QFZT capsule has the potential clinical application of in OA therapy.
The QFZT capsule can improve the symptoms of the OA in rodent animal rats by attenuating pain and retarding cartilage damage. This study indicated that the QFZT capsule has the potential clinical application of in OA therapy.Prevention of amputation has become a key objective of clinicians providing care to patients with high-risk diabetic foot problems. In this regard, the multidisciplinary diabetic foot team (MDFT) has been embraced as the most effective way to manage patients with foot ulcers, infections, and Charcot feet. Importantly, such specialized teams have also integrated various surgical specialties to enable more expedient management of these often complex conditions. Experienced diabetic foot surgeons over the last three or four decades have contributed much to this discipline, whereby foot-sparing reconstructive procedures or minor amputations have become fundamental strategies for limb preservation teams. Central to limb salvage, of course, is the recognition of underlying vascular insufficiency and the importance of prompt (endo)vascular intervention. Restoration of adequate perfusion is essential to allow the podiatric, orthopaedic, or plastic surgeon to perform indicated functional reconstructive or minor amputation procedures. This evidence-based overview discusses the various indications and surgical principles inherent in modern concepts aimed at preventing amputation in the high-risk diabetic foot.
The standard proximal interlocking screw (SS) configuration for antegrade intramedullary nail (IMN) fixation of femoral shaft fractures is lateral to medial or from the greater to less trochanter. Some authors argue for the routine use of the reconstruction screw (RS) configuration (oriented up the femoral neck) instead to prevent femoral neck complications. The purpose of this study was to compare a matched cohort of patients receiving these screw configurations and subsequent complications.

A retrospective review of two urban level-one trauma centers identified adults with isolated femoral shaft fractures undergoing antegrade IMN. Patients with RS and SS configurations were matched 11 by age, sex, fracture location, and AO classification in order to compare complications.

130 patients with femoral shaft fractures were identified. SS and RS configurations were used in 83 (64%) and 47 (36%) patients. 30 patients from each group were able to be matched for analysis. The RS and SS group did not differ in age, fracture location, AO classification, operative time, or number of distal interlocking screws. The RS group had fewer open fractures and were more likely to have two proximal screws. There were 7 complications, including 5 nonunions and 2 delayed unions, with no detectable difference between RS vs. SS groups (10% vs 13%, Proportional difference-3%, 95% confidence interval (CI)-30 to 14%, p=0.1). There were no femoral neck complications in the entire cohort of 130 patients. On multivariate analysis none of the variables analyzed were independently associated with the development of complications.

In this matched cohort of patients with femoral shaft fractures undergoing antegrade IMN fixation, RS and SS configurations were associated with a similar number of complications and no femoral neck complications. The SS configuration remains the standard for antegrade IMN femoral shaft fixation.

Level III, Retrospective cohort study.
Level III, Retrospective cohort study.Various techniques of reconstruction of deformed Charcot hindfoot using different internal fixation devices have been described in the literature. We present our surgical technique using specific principles that has resulted in improved outcomes to allow correction of deformity, obtain stability and allow progression to weightbearing in orthotic shoes. We describe our preoperative evaluation, planning and surgical timing. We also hope to share some technical pearls and details on the finer points to achieve a satisfactory correction and reduce the learning curve.Open anatomic reconstruction of the lateral ligament (AntiRoLL) of the ankle with a gracilis Y graft and the inside-out technique are commonly used and have evolved to minimally invasive surgery, including arthroscopic AntiRoLL (A-AntiRoLL) and percutaneous AntiRoLL procedures. A-AntiRoLL allows assessment and treatment of intra-articular pathologies of the ankle concurrently with stabilization. However, the A-AntiRoLL technique is technically demanding, especially in the process of calcaneofibular ligament reconstruction under subtalar arthroscopy. In contrast, the percutaneous AntiRoLL procedure is a simple concept that does not require the skill of an experienced arthroscopist but requires an extra skin incision to assess and treat intra-articular pathologies of the ankle. This study describes the application of a minimally invasive anatomic reconstruction technique-hybrid AntiRoLL-for chronic instability of the ankle that does not require advanced arthroscopic technique to assess and treat intra-articular pathology simultaneously.
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