MicroRNA-34a (miR-34a) is a tumor suppressor that has attracted considerable attention in recent years. It modulates cancer cell invasion, metastasis, and drug resistance, and has also been evaluated as a diagnostic and/or prognostic biomarker. A number of targets of miR-34a have been identified, including some other non-coding RNAs, and it is believed that the modulation of these myriads of targets underlines the versatile role of miR-34a in cancer progression and pathogenesis. Seemingly appealing results from preclinical studies have advocated the testing of miR-34a in clinical trials. However, the results obtained are not very encouraging and there is a need to re-interpret how miR-34a behaves in a context dependent manner in different cancers. In this review, we have attempted to summarize the most recent evidence related to the regulation of different genes and non-coding RNAs by miR-34a and the advances in the field of nanotechnology for the targeted delivery of miR-34a-based therapeutics and mimics. With the emergence of data that contradicts miR-34a’s tumor suppressive function, it is important to understand miR-34a’s precise functioning, with the aim to establish its role in personalized medicine and to apply this knowledge for the identification of individual patients that are likely to benefit from miR-34a-based therapy.

Globally, cervical cancer is the fourth most common cancer in women and the seventh most common cancer overall, accounting for an estimated 300 000 annual deaths. Human papillomavirus (HPV) is the second most common cause of cervical cancer worldwide. HPV screening is not a common practice in Pakistan. The aim of this study was to determine the prevalence of HPV and HPV types in women with a normal cytology of the cervix living in the upper and lower regions of Punjab, Pakistan, and to analyze the risk factors for HPV in this region. PCR analysis was performed for 1011 female patients with a normal cytology of the cervix from various districts of Punjab Province, Pakistan. Risk factors for the acquisition of HPV were studied. High-risk HPV types (HPV16 and HPV18) were detected using the Abbott Real Time HR HPV test. To determine the genotype, partial L1 region sequences of HPV-positive samples were subjected to sequencing using MY/09/MY11 primers, and a phylogenetic tree was constructed using CLC software. The study found a 4.74% prevalence of HPV, with the most frequent HPV type found being the low-risk HPV6 (in 25% of infected individuals), followed by HPV55 (22.9%), HPV11 (20.8%), and high-risk types HPV45 (12.5%), HPV33 (8.33%), HPV18 (6.25%), and HPV16 (4.16%). Phylogenetic analysis of all HPV types in this study showed 80-99% nucleotide identity with types related to the same species. The sequences were clustered with China, India, Mexico, Iran, Slovenia, and Germany, showing the diversity in origin of the various genotypes prevalent in Pakistan. In this population with a normal cervical cytology, the prevalence of high-risk HPV types was very low. The major prevalent HPV genotype in Punjab Province of Pakistan was the low-risk HPV type 6, followed by HPV type 55. Sequencing of the partial L1 region suggested that the region was highly conserved in all reported sequences. This study highlights the need to conduct robust epidemiological studies in the region and to develop regular HPV screening so that the situation does not reach an alarming stage resulting in cervical cancer.

Hybrid organic–inorganic halide perovskites (HOIPs) have recently represented a material breakthrough for optoelectronic applications. Obviously, studying the interactions between the central organic cation and the Pb-X inorganic octahedral could provide a better understanding of HOIPs. In this work, we used a first-principles theoretical study to investigate the effect of different orientations of central formamidinium cation (FA⁺) on the electronic and optical properties of FAPbBr₃ hybrid perovskite. In order to do this, the band structure (with and without spin–orbit coupling (SOC)), density of states (DOS), partial density of states (PDOS), electron density, distortion index, bond angle variance, dielectric function, and absorption spectra were computed. The findings revealed that a change in the orientation of FA⁺ caused some disorders in the distribution of interactions, resulting in the formation of some specific energy levels in the structure. The interactions between the inorganic and organic parts in different directions create a distortion index in the bonds of the inorganic octahedral, thus leading to a change in the volume of PbBr₆. This is the main reason for the variations observed in the electronic and optical properties of FAPbBr₃. The obtained results can be helpful in solar-cell applications.

Rosa webbiana L. (Rosaceae) is one of the least reported and most understudied members of this family. It is native to the Himalayan regions of Pakistan and Nepal. The anti-convulsant effect of n-hexane extract of fruit of Rosa webbiana was investigated in a pentylenetetrazole (PTZ)-induced animal model of epilepsy. Male Sprague-Dawley rats were divided into six groups (n = 7) including control, PTZ (40 mg/kg), diazepam (4 mg/kg) and n-hexane extract (at 50, 150 and 300 mg/kg). Convulsive behavior was observed and resultant seizures were scored, animals sacrificed and their brains preserved. Chitosan nanoparticles were prepared using the ionic gelation method and characterized by UV-analysis, zeta potential and Fourier transform infrared spectroscopy (FTIR). The effects of all the treatments on the expression of phosphorylated cytokine tumor necrosis factor α (p-TNF-α) and phosphorylated transcription factor nuclear factor kappa B (p-NF-κB) expression in the cortex and hippocampus of the brains of treated rats were studied through enzyme linked immunosorbent assay (ELISA) and morphological differences and surviving neuronal number were recorded through hematoxylene and eosin (H&E) staining. Significant changes in seizures score and survival rate of rats were observed. Downregulation of neuro-inflammation, p-TNF-α and p-NF-κB was evident. Gas Chromatography-Mass Spectrometry (GC-MS) analysis of this fraction showed multiple constituents of interest, including esters, alkanes and amines.

Metabolic disorders often lead to cardiac complications. Metabolic deregulations during diabetic conditions are linked to mitochondrial dysfunctions, which are the key contributing factors in cardiac hypertrophy. However, the underlying mechanisms involved in diabetes-induced cardiac hypertrophy are poorly understood. In the current study, we initially established a diabetic rat model by alloxan-administration, which was validated by peripheral glucose measurement. Diabetic rats displayed myocardial stiffness and fibrosis, changes in heart weight/body weight, heart weight/tibia length ratios, and enhanced size of myocytes, which altogether demonstrated the establishment of diabetic cardiac hypertrophy (DCH). Furthermore, we examined the expression of genes associated with mitochondrial signaling impairment. Our data show that the expression of PGC-1α, cytochrome c, MFN-2, and Drp-1 was deregulated. Mitochondrial-signaling impairment was further validated by redox-system dysregulation, which showed a significant increase in ROS and thiobarbituric acid reactive substances, both in serum and heart tissue, whereas the superoxide dismutase, catalase, and glutathione levels were decreased. Additionally, the expression levels of pro-apoptotic gene PUMA and stress marker GATA-4 genes were elevated, whereas ARC, PPARα, and Bcl-2 expression levels were decreased in the heart tissues of diabetic rats. Importantly, these alloxan-induced impairments were rescued by N-acetyl cysteine, ascorbic acid, and selenium treatment. This was demonstrated by the amelioration of myocardial stiffness, fibrosis, mitochondrial gene expression, lipid profile, restoration of myocyte size, reduced oxidative stress, and the activation of enzymes associated with antioxidant activities. Altogether, these data indicate that the improvement of mitochondrial dysfunction by protective agents such as N-acetyl cysteine, selenium, and ascorbic acid could rescue diabetes-associated cardiac complications, including DCH.

Epilepsy is a chronic neurological disorder characterized by recurrent unprovoked seizures. Currently available antiepileptic drugs have severe side effects and do not offer complete cure. Herbal remedies have been used for centuries to treat many neurodegenerative disorders. Otostegia limbata L. belongs to the largest and medicinally important family Lamiaceae and is distributed in hilly areas of Pakistan. This study was designed to assess the antioxidant, anti-inflammatory, and anticonvulsant potential of O. limbata. The methanolic extract showed significant antioxidant activity assessed by (1,1-diphenyl 2-picrylhydrazyl) free-radical scavenging assay, nitric oxide scavenging, and iron chelation antioxidant assays. The methanolic extract was evaluated for its anticonvulsant effect, employing the pentylenetetrazole (PTZ)-induced mice model of epilepsy. Three different doses of O. limbata (100, 200, and 300 mg/kg) were administered orally 30 min before PTZ [50 mg/kg, intraperitoneal (i.p.)] injection, while diazepam was used as a positive control. The extract at 300 mg/kg significantly decreased the duration and increased the latency of the PTZ-induced seizures. The expression of inflammatory cytokines tumor necrosis factor α (p-TNF-α) and phosphorylated transcription factor nuclear factor kappa B (p-NF-κB), in the cortex and hippocampus of the brains of treated mice were analyzed through enzyme-linked immunosorbent assay and western blot analysis. The morphological changes and number of surviving neurons were recorded through hematoxylin and eosin staining. The seizure score and survival rate of the treated group showed considerable differences as compared to the PTZ group. TNF-α and p-NF-K b expression were downregulated as compared to the PTZ group. The anticonvulsant effect may be the outcome of the antioxidant potential and high levels of phenols and flavonoids detected in the methanolic plant extract through Fourier transform infrared spectrophotometer and gas chromatography–mass spectrometry analysis.